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  • 2005-2009
  • 1995-1999  (172)
  • 1980-1984  (238)
  • 1955-1959
  • 1920-1924
Jahr
  • 101
    ISSN: 1432-1106
    Schlagwort(e): Malnutrition ; Hippocampus ; Dendrites ; Degeneration ; Regrowth ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We have recently shown that lengthy periods of low-protein feeding of the adult rat lead to deficits in the number of hippocampal granule and pyramidal cells, and in the number of mossy fiber synapses. These findings prompted us to analyze the dendrites of these neurons to evaluate whether, under the same experimental conditions, degenerative and/or plastic changes also take place at the dendritic level. The hippocampal formations from five 8-month-old rats fed a low-protein diet (casein 8%) for 6 months from the age of 2 months and from five age-matched controls were Golgi-impregnated and the morphology of the dendritic trees quantitatively studied. We found that in malnourished animals there was a reduction in the number of dendritic branches in the dentate granule cells and in the apical dendritic arborizations of CA3 pyramidal neurons. In addition, in the dentate granule cells the spine density was markedly increased and the terminal dendritic segments were elongated in malnourished animals. No alterations were found in the apical dendrites of CA1 pyramidal cells. The results obtained show that long periods of malnutrition induce marked, although not uniform, changes in the dendritic domain of the hippocampal neurons, which reflect the presence of both degenerating and regrowing mechanisms. These alterations are likely to affect the connectivity pattern of the hippocampal formation and, hence, the activity of the neuronal circuitries in which this region of the brain is involved.
    Materialart: Digitale Medien
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  • 102
    ISSN: 1432-1106
    Schlagwort(e): Transplantation immunology ; Spinal cord ; Cortex ; Ramified and reactive microglia ; Intraocular ; transplantation ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract While the central nervous system (CNS) has been characterized as an immunologically privileged site, there are also several reports describing immunological reactions within the CNS. A certain degree of immunological privilege has also been ascribed to the anterior chamber of the eye. We have used the intraocular transplantation model to study immunological reactions in transplants of embryonic neural tissue. Outbred SpragueDawley rats and inbred Fisher rats were used. Pieces of rat parietal cortex or the cervical spinal cord were prepared from embryonic day 14 and implanted into the eye chambers of adult rats of the same strain. Following intraocular maturation, grafts were analysed using antibodies against: major histocompatibility complex (MHC) class I, MHC class II; rat antigens CD4, CD8, CD11b; T-cell receptor; rat antigen ED1; and glial fibrillary acidic protein. Using this set of markers for immunological reactions, transplants were scored on a blind basis. We found no significant differences in immunological scores between transplants obtained from different litters of fetuses of the outbred animals. Grafting in the outbred strain led to increased numbers of immunologically reactive cells in the grafts. This was not seen in grafts in the inbred strain. Spinal cord transplants led to a significantly higher degree of cytotoxic immunity-related cells expressing MHC class II as well as CD4-positive cells. There was a positive correlation between ED1 negativity and well-developed ramified microglia. From these results we conclude also that well-developed intraocular CNS tissue grafts do contain cellular evidence of immunological events and that different areas of the CNS may provoke different degrees of response. Reactive microglial proliferation appears to be one of the most sensitive ways to monitor the immunological condition of grafted CNS tissue.
    Materialart: Digitale Medien
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  • 103
    ISSN: 1432-1106
    Schlagwort(e): Glutamate receptor ; Cerebral cortex ; White matter ; Electron microscopy ; Development ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The distribution of the [3H]alpha-amino-3-hydroxy-5-methylisoxzalepropionic acid (AMPA) receptor subunit GluR4 was studied in frontal, parietal and temporal cerebral cortex, subcortical white matter and corpus callosum of neonatal, immature and mature rats. In 1-to 2-day-old rats, a few oligodendrocyte progenitors and amoeboid microglia in the supraventricular part of the corpus callosum were immunolabelled for GluR4. At 7 to 10 days, the number of amoeboid microglia and oligodendrocyte progenitors in white matter increased; many neurons in cortex, including pyramidal neurons, were also moderately labelled for GluR4. The pattern of GluR4 immunostaining in 14-day-old rats was different from that in 7-to 10-day-old rats, but similar to the adult, in that there was no immunoreactivity in microglia and oligodendrocyte progenitors in subcortical white matter. A proportion of non-pyramidal neurons in cortex were moderately labelled, while some pyramidal neurons were lightly labelled. A population of small glial cells with features of oligodendrocyte progenitors were densely labelled in cortex.
    Materialart: Digitale Medien
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  • 104
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 111 (1996), S. 30-34 
    ISSN: 1432-1106
    Schlagwort(e): Dorsal root ganglion cells ; Capsaicin ; Cell diameter ; IH ; Action potential ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects of capsaicin were tested on 221 acutely isolated dorsal root ganglion neurons of the rat, which ranged in diameter from 15 to 55 μm. In a subpopulation of these cells, ranging in diameter from 17.5 to 33 μm (n=117), capsaicin (1 μM) produced an inward shift in holding current that was associated with an increase in membrane conductance in most cells (114 of 117). These effects of capsaicin were reversible upon washout of the drug. Other cells ranging in diameter from 15 to 52.5 μm (n=104) were unaffected in this manner by the 1 μm concentration of capsaicin. Capsaicin-sensitive cells had, on average, significantly longer duration action potentials and expressed significantly less IH than capsaicin-insensitive cells. The relatively long duration action potentials and/or small cell body diameter and paucity of IH observed in most of the capsaicin-sensitive cells is consistent with their representing C- or Aδ-type sensory neurons.
    Materialart: Digitale Medien
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  • 105
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 111 (1996), S. 169-177 
    ISSN: 1432-1106
    Schlagwort(e): Buccal stretch receptor ; Development ; Static sensitivity ; Masticatory muscles ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Postnatal functional and structural development of the buccal stretch receptor (BSR) of rats was investigated, using electrophysiological and morphological techniques. For functional analysis, sustained discharges in response to ramp-and-hold stretches were recorded from the BSRs isolated from animals aged 10 days to 10 weeks. The threshold amplitude of stretch for a sustained discharge fell significantly between 10 days and 3 weeks, reaching adult values at 5 weeks of age, while the static sensitivity increased conspicuously between 2 and 4 weeks after birth. On the other hand, between 1 and 4 weeks of age, apparent structural changes in the BSR were observed on the number of preterminal branches in a sensory unit, the size of the varicose-like swellings along the terminal axon, the density of collagen and elastic fibers around the core structure, and the content of the sub-capsular space. From these results, we suggest that the increase in the density of the connective tissue around the core structure is associated with an enhancement in the elasticity of the BSR in the early postnatal stages, decreasing the threshold amplitude of stretch for a sustained discharge. One possible explanation for the maturation of the static sensitivity of this receptor is growth of the sensory axon terminals filled with dense mitochondria.
    Materialart: Digitale Medien
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  • 106
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 111 (1996), S. 371-384 
    ISSN: 1432-1106
    Schlagwort(e): Purkinje cell ; Estradiol ; Network ; Performance ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Neuromodulation of Purkinje (Pnj) cell responses by monoamines and estrous hormones is well characterized in the cerebellum at the cellular level, but not at the level of neuronal circuits in the awake behaving animal. In the present study, simultaneous recordings of up to 16 single neurons from within the olivo-cerebellar circuit were obtained through chronically implanted microwire electrode bundles: arrays of Pnj cell like neurons (Pnj cln) in the paravermal cerebellum and neurons within the afferent source of its climbing fiber input, the rostral dorsal accessory olive (rDAO), were recorded simultaneously across 3–20 consecutive estrous cycles during constant or variable speed treadmill locomotion performance tasks. Over 90% of Pnj cln recorded during treadmill locomotion exhibited significant increases (80%) or decreases (10%) in activity correlated with the stance phase of locomotion. In contrast, cells from the rDAO increased activity during speed changes or when the rat failed to maintain the treadmill speed (position slip). On the night of behavioral estrus, which is triggered by elevations in circulating levels of 17β-estradiol and progesterone, the magnitude of both increases and decreases in stance-correlated Pnj cln activity increased by 85–115%. These results are consistent with our previous findings that 17β-estradiol and progesterone enhance excitatory and inhibitory responses of single Pnj cells to locally applied glutamate and GABA, respectively. This dual enhancement of both excitatory and inhibitory effects, apparently paradoxical at the cellular level, produced a marked heightening of the contrast of the neural population “signal” at the neuronal ensemble level. Furthermore, the stance-correlated discharge of Pnj cln during estrus preceded that during diestrus by ∼120ms. Frame-by-frame video analysis also suggested that the swing phase of the step cycle was shortened on estrus compared with diestrus (low hormone state). In addition, rDAO discharge correlated with speed change or position slip was also significantly increased (P〈0.05) on the night of behavioral estrus versus diestrus. Thus, estrus was associated with changes in both the amplitude and the timing of Pnj cln and rDAO discharge correlated with specific behavioral events. These estrous-associated changes in Pnj cell activity were well correlated (r = 0.84) with faster responses to random changes in treadmill speed, a motor performance task. Together, these findings suggest that the increases in the contrast of stancecorrelated Phj cln discharge observed following peak circulating levels of sex steroid hormones are associated with improved motor performance on a randomly moving treadmill.
    Materialart: Digitale Medien
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  • 107
    ISSN: 1432-1106
    Schlagwort(e): Tachykinin receptor ; Retrograde cell labeling ; Optic nerve crush ; Ganglion cell layer ; Inner nuclear layer ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Substance P receptor is known to provide a principal interface between tachykinin peptides and tachykinin-sensitive cells in retinal circuitry and to produce several physiological functions such as excitation of ganglion cells. We reported results of in situ hybridization analysis of substance P receptor in rat retina using digoxigenin-labeled RNA probes to yield discrete cell labeling. Distinct hybridization signal was present in a great majority of ganglion cells that provide retinal fibers to a central target. It was also present in a subpopulation of amacrine cells. Following optic nerve crush, ganglion cells lost their hybridization signal in a time-dependent manner, while hybridization-positive amacrine cells were persistently seen. From the results, we identified the hybridization message as distinctly localized to two systems, output cells and intrinsic cells in retinal circuitry.
    Materialart: Digitale Medien
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  • 108
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 110 (1996), S. 21-27 
    ISSN: 1432-1106
    Schlagwort(e): Long-term potentiation ; Auditory cortex ; Pyramidal cell ; NMDA receptor ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In supragranular layers of the rat auditory cortex, white matter stimulation produces antidromic and transsynaptic field potentials, of which only the latter shows long-term potentiation (LTP) following tetanic stimulation of the white matter. In this study, we investigated the cells responsible for the LTP. The transsynaptic field potentials, excitatory postsynaptic potentials (EPSPs), and orthodromic spikes were blocked by 6-cyano-7-nitroquinoxaline-2, 3-dione (10 μM), but not by d-2-amino-5-phosphonovalerate (D-AP5, 50 μM). The latency of EPSPs was constant, while that of transsynaptic field potentials and orthodromic spikes was shortened by the increase in stimulus intensity. Appearance of anti-dromic field potentials and antidromic spikes at strong stimulus intensities were accompanied by reduction in amplitude of transsynaptic field potentials and elimination of orthodromic spikes, respectively. Morphological identification of neurons showing antidromic spikes by intracellular injection of biocytin revealed that most of them were supragranular pyramidal cells. The effects of tetanic stimulation were studied by intracellular recording in seven neurons showing, antidromic spikes, and it was found that only two of them showed LTP of EPSP slope. However, in all of the other eight units showing antidromic spikes and recorded extracellularly, LTP was clearly observed in orthodromic firing probability. The LTP induction in the orthodromic firing probability was blocked by D-AP5. These findings indicate that the LTP in field potentials corresponds to LTP in supragranular pyramidal outputs, and the input-output relationship in neural networks of the adult rat auditory cortex is strongly modulated by LTP.
    Materialart: Digitale Medien
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  • 109
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 112 (1996), S. 431-441 
    ISSN: 1432-1106
    Schlagwort(e): Plasticity ; Auditory cortex ; Neuronal assemblies ; Microstimulation ; Cortical maps ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Single neurons, acting alone, cannot account for the complex and rapid computations that are routinely accomplished by the behaving nervous system. Recent studies with separable multineuron recordings are showing that neuronal assemblies can indeed be detected and that their organization is very dynamic, depending on variables such as time, physical stimulus, and context. Here we explore both single-neuron and assembly properties in the rat's auditory cortex. Acoustic stimuli are used as a normal, physiological input, and weak electrical intracortical microstimulation (ICMS) as a perturbation that forces a rapid cortical reorganization. In this setting, various aspects of neuronal interactions are changed by the ICMS. We found that cortical neurons exhibited highly synchronous oscillatory firing patterns that were enhanced by ICMS. Cross-correlation studies between two spike trains showed that statistically significant correlations depended on the anatomical distance between the two neurons. ICMS changed the strength and the local number of such correlations. Joint petristimulus analysis and gravity analysis showed that the correlation between neuronal activities varied dynamically at several time scales. We have identified neuronal assemblies in two ways, defined through similarity of receptive field properties and defined through correlated firing. Close anatomical spacing between neurons was conducive to, but not sufficient for membership in, the same assembly with either definition. ICMS changed cortical organization by altering assembly membership. Our data show that neuronal assemblies in the rat auditory cortex can be established transiently in time and that their membership is dynamic.
    Materialart: Digitale Medien
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  • 110
    ISSN: 1432-1106
    Schlagwort(e): Infraorbital nerve ; Barrels ; Trigeminal ; Immunocytochemistry ; Peptides ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Previous studies in adult animals have suggested that the peptides galanin and neuropeptide Y (NPY) may be upregulated in the same primary afferent neurons after peripheral axotomy. The present study was undertaken to determine whether such upregulation occurred in vibrissae-related primary afferent neurons and their axons after damage to the infraorbital nerve [ION; the trigeminal (V) branch that innervates the vibrissae follicles]. Double-labelling experiments demonstrated that approximately 75% of axotomized V ganglion cells and the central arbors of vibrissae-related primary afferents expressed both galanin and NPY after perinatal, but not adult, nerve damage. However, additional experiments demonstrated that the sensitive periods for lesion-induced upregulation of the two peptides and the period over which they were expressed after neonatal ION transection differed substantially. Staining for both peptides was increased after ION damage on P-0 through P-14, but only galanin staining was increased in vibrissae-related primary afferents after lesions on P-21. Galanin expression was elevated in vibrissae-related primary afferents in rats killed 3,8, and 15 days after neonatal ION transection, while increased NPY was observed at only the middle time point. The lesion-induced increases in galanin and NPY in vibrissae-related ION primary afferents suggest that these peptides may modulate central V reorganization after such damage.
    Materialart: Digitale Medien
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  • 111
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 108 (1996), S. 285-296 
    ISSN: 1432-1106
    Schlagwort(e): Acetylcholine ; Amygdala ; Basal forebrain ; Electrocorticogram ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In urethane-anesthetized rats, electrical 100-Hz stimulation of the basal amygdala changed neocortical electrical activity from 6-Hz or less large-amplitude, irregular slow activity to low-voltage fast activity (LVFA) including frequencies of above 10 Hz. A similar activating effect was seen in the hippocampus, where amygdala stimulation induced the appearance of rhythmical slow activity in the 2 to 6-Hz range. This activation of neocortical and hippocampal activity by amygdala stimulation was blocked by the cholinergic-muscarinic receptor antagonist scopolamine (0.5–5.0 mg/kg i.p.), but not by the peripheral antagonist methylscopolamine, in a concentration-dependent manner. In contrast, a blockade of ascending inputs from the midbrain to the neocortex by treatment with the serotonin-depletor p-chlorophenylalanine or cauterization of the rostral midbrain did not block neocortical LVFA to amygdala stimulation, even though the lesions abolished all LVFA to strong noxious stimuli such as tail pinches. Unilateral infusions of the local anesthetic lidocaine (1%) into the basal forebrain selectively blocked LVFA in the neocortex ipsilateral to the infusion. However, intracerebral or systemic administration of various excitatory amino acid antagonists (2-amino-5-phosphonovaleric acid, kynurenic acid, NPC 12626) was not effective in blocking LVFA to amygdala stimulation. An input from the amygdala to the basal forebrain cholinergic system appears to be one of multiple systems involved in the cholinergic activation of neocortical and hippocampal activity. Further, basal forebrain-cholinergic inputs to the cerebrum alone are sufficient to activate the electrocorticogram, as they sustain activation even in the absence of inputs from the mesencephalon.
    Materialart: Digitale Medien
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  • 112
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 109 (1996), S. 17-21 
    ISSN: 1432-1106
    Schlagwort(e): Circling ; Habenula ; Apomorphine ; Haloperidol ; Dopamine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Apomorphine, 2 mg/kg (s.c.) produced significant contralateral turning in rats with unilateral radiofrequency lesions of the habenula nucleus over a test period of 60 min when tested at post-surgery days 3, 7, and 14. Levels of contralateral circling were not significantly increased when the animals were tested on days 21 and 28, although a contralateral bias was still observed. Rotation induced by apomorphine was completely blocked by the administration of haloperidol (0.3 mg/kg i.p.), and there was no behavioural asymmetry in lesioned animals following administration of saline or a high dose of haloperidol (2 mg/kg i.p.). These results indicate that unilateral habenula lesions lead to imbalance of dopaminergic activity, which is expressed as contralateral circling when the animal is challenged with apomorphine.
    Materialart: Digitale Medien
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  • 113
    ISSN: 1432-1106
    Schlagwort(e): Sensory neurons ; Proto-oncogenes ; Corneal pain ; Calcium channel blockers ; Diltiazem ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The distribution and number of trigeminal brainstem and higher order sensory neurons expressing the protein product of the proto-oncogene c-fos after noxious stimulation of the cornea was studied in the rat using immunocytochemistry. The possibility that attenuation of nociceptive messages from the cornea by diltiazem reduced Fos-like immunoreactivity of spinal trigeminal neurons was also examined. A group of animals were killed 2–3 h after corneal stimulation. One cornea was stimulated with: a drop of 10 mM acetic acid; with acid plus mechanical scratching of the corneal epithelium; or with a drop of saline at 56 ° C. Half of the animals treated with acid had been pretreated ipsilaterally with topical diltiazem (10 mM). Control rats received either saline in one eye or no treatment. Another group of animals were killed 7–8 h after stimulation with acetic acid. Fos-like immunoreactive neurons were counted in serial brain-stem sections using an anti-Fos primary antiserum and processed according to the avidin-biotin complex method. In rats killed 2–3 h after corneal stimulation with acid, heat, or acid plus mechanical injury, labelled neurons were found in laminae I and II of the intermediate zone between caudalis and interpolaris subnuclei of the ipsilateral spinal trigeminal nucleus and, in a reduced number, in the symmetrical zones of the contralateral side. In animals stimulated with noxious heat or combined mechanical and chemical injury, a few scattered cells were also labelled in the ipsilateral junction between the cervical spinal cord and the caudalmost part of the trigeminal subnucleus caudalis. In rats killed 7 h after stimulation with acid, stained neurons were observed in the same areas of the trigeminal nucleus as in rats killed at shorter times, but in lower numbers; in these animals, no immunoreactive cells were found in deeper laminae or in higher sensory relay nuclei. Pretreatment with diltiazem significantly reduced the number of cells of the spinal trigeminal nucleus labelled after corneal stimulation with acid. The results indicate that brief noxious stimulation of the cornea evoke expression of c-Fos in neurons of the spinal trigeminal complex. Diminution by diltiazem of the number of immunreactive neurons activated by corneal irritation suggests that this drag, by reducing chemosensitivity of nociceptive terminals, decreases nociceptive inflow to central nervous structures involved in ocular pain perception.
    Materialart: Digitale Medien
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  • 114
    ISSN: 1432-1106
    Schlagwort(e): Urinary bladder ; Inflammation ; Brainstem ; Pontomesencephalic junction ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The evoked expression of the immediate early gene encoded proteins c-Fos and Krox-24 was used to study activation of hindbrain neurons as a function of the development of Cyclophosphamide (CP) cystitis in behaving rats. CP-injected animals received a single dose of 100 mg/kg i.p. under transient volatile anesthesia and survived for 1 to 4 h in order to cover the whole postinjection period during which the disease develops. CP-injected groups included: (1) animals with minor simple chorionic edema, an early characteristic of inflammation (1 h postinjection); (2) animals with well developed simple chorionic edema (2 h postinjection); (3) animals with mild inflammation (chorionic edema accompanied by epithelial cleavage; 3 h postinjection); and (4) animals with complete inflammation (4 h postinjection). In addition to onset of chorionic edema, the earliest postinjection period also included the general aspects of the nervous reaction consecutive to the injection process (handling, transient volatile anesthesia and postanesthesia awakening, abdominal pinprick, CP blood circulating effects). Controls included both noninjected animals and saline injected animals surviving for the same times as CP injected ones. Quantitative results come from c-Fos expression. It has been shown that: (1) saline injection is a significant stimulus for only nucleus O and central gray pars alpha and nucleus medialis of the dorsal vagal complex; (2) all structures driven by CP injection (nucleus O and central gray pars alpha, locus coeruleus, Barrington's nucleus and parabrachial area mostly in its ventral and lateral subdivisions, dorsal vagal complex, ventrocaudal portion of lateral bulbar reticular formation) responded vigorously shortly after injection, but only two (dorsal vagal complex, ventrocaudal portion of lateral bulbar reticular formation) showed increased or renewed activity when cystitis completely developed, i.e., when noxious visceral inputs reached highest levels. Regarding the sequential activation of these structures in relation to postinjection time, evidence is given that: (1) a large variety of hindbrain structures are differentially involved in either the general reaction consecutive to the injection process or to various degrees of cystitis; (2) these structures extend from the brain spinal cord to the pons mesencephalon transitional junction levels; (3) the two structures most powerfully driven by visceronociceptive inputs are also the most caudal ones, being located at the brain spinal cord junction level; and (4) the dorsal vagal complex could be the main hindbrain visceral pain center, with three particular subdivisions, the nucleus medialis, nucleus commissuralis, and ventralmost part of area postrema, being involved.
    Materialart: Digitale Medien
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  • 115
    ISSN: 1432-1106
    Schlagwort(e): Calcium ; Hippocampal slice ; CA1 ; ω-Agatoxin IVA ; ω-Conotoxin GVIA ; ω-Conotoxin ; MVIIC ; Nimodipine ; Ethosuximide ; Trimethadion ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The contribution of T-, L-, N-, P-, and Q-type Ca2+ channels to pre-and postsynaptic Ca2+ entry during stimulus-induced high neuronal activity in area CA1 of rat hippocampal slices was investigated by measuring the effect of specific blockers on stimulus-induced decreases in extracellular Ca2+ concentration ([Ca2+]0). [Ca2+]0 was measured with ion-selective electrodes in stratum radiatum (SR) and stratum pyramidale (SP), while Ca2+ entry into neurons was induced with stimulus trains (20 Hz for 10 s) alternately delivered to SR and the alveus, respectively. The [Ca2+]0 decreases recorded in SR in response to SR stimulation represented mainly presynaptic Ca2+ entry (Capre), while [Ca2+]0 decreases recorded in SP in response to alvear stimulation were predominantly based on postsynaptic Ca2+ entry (Capost). Ethosuximide and trimethadione were ineffective m concentrations up to 1 mM. At 10 mM, they reduced Capost and, much less, also Capre Nimodipine (25 μM) reduced Capost and, to a minor extent, Capre. ω-Agatoxin IVA (0.4–1 μM) and ω-conotoxin MVIIC (1 μM) also reduced both Capre and Capost, but with a stronger action on Capre. ω-Conotoxin GVIA (3–8 μM) reduced Capost without effect on Capre. We conclude that during stimulus-induced, high-frequency neuronal activity Capost is carried by P/Q-, N-, and L-type channels and probably a further channel type different from these channels. Capre includes at least P/Q-and possibly L-type channels. N-type channels did not contribute to Capre in our experiments. Since ethosuximide and trimethadione were only effective in high concentrations, their action may be unspecific. Thus, T-type channels do not seem to play a major part in Ca2+ entry in this situation.
    Materialart: Digitale Medien
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  • 116
    ISSN: 1432-1106
    Schlagwort(e): Cerebral ischemia ; Magnetic resonance imaging ; Hyperglycemia ; Diffusion imaging ; Reperfusion ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The early evolution of ischemic brain injury under normoglycemic and streptozotocin-induced hyperglycemic plasma conditions was studied using magnetic resonance imaging (MRI). Male Sprague-Dawley rats were subjected to either permanent middle cerebral artery occlusion (MCAO), or 1-h MCAO followed by reperfusion using the intraluminal suture insertion method. The animals were divided into four groups each with eight rats: normoglycemia with permanent MCAO, normoglycemia with 1-h MCAO, hyperglycemia with permanent MCAO, and hyperglycemia with 1-h MCAO. Diffusion-weighted images (DWIs) and T2-weighted images (T2WIs) were aquired every l h from 20 min until 6 h after MCAO, at which time cerebral plasma volume images (PVIs) were acquired. Tissue infarction was determined by triphenyltetrazolium chloride staining at 7 h after MCAO. The ischemic damage, measured as the area of DWI and T2WI hyperintensity and tissue infarction, increased significantly in hyperglycemic rats in both permanent and transient MCAO models. In the permanent MCAO model, the maximal apparent water diffusion coefficient (ADC) decline under either normoor hyperglycemia was about 40%, but the speed of ADC drop was faster in hyperlgycemic rats than in normoglycemic rats. Reperfusion after l h of MCAO in normoglycemic rats partly reversed the decline in ADC, whereas the low ADC area continued to expand after reperfusion in the hyperlgycemic group. Between the two hyperglycemic groups with either permanent MCAO or reperfusion, no significant difference was found in the infarct volume measured at 7 h after MCAO. However, reperfusion dramatically increased the extent and accelerated the development rate of vasogenic edema. ADC in the hyperglycemic reperfusion group also dropped to a lower level. A large “no-reflow” zone was found in the ischemic hemisphere in the hyperglycemic reperfusion group. This study provides strong evidence to support that preischemic hyperglycemia exacerbates ischemic damage in both transient and permanent MCAO models and demonstrates, using MRI, that reperfusion under preischemic hyperglycemia accelerates the evolution of early ischemic injury.
    Materialart: Digitale Medien
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  • 117
    ISSN: 1432-1106
    Schlagwort(e): Differential-pulse voltammetry ; Dopamine ; Caudate putamen ; Neural grafting ; Non-grafted side ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The present study employed differential-pulse voltammetry to assess the influence of foetal ventral mesencephalic grafts on dopamine overflow in the contralateral caudate putamen of the 6-hydroxydopamine rat model of Parkinson's disease. The experimental design involved measurements of dopamine overflow in the grafted and contralateral striatum. Control measurements of dopamine overflow were performed in 6-hydroxydopamine-lesioned rats only and the caudate putamen of normal control rats. Cell suspensions of foetal rat ventral mesencephalic tissue were grafted into the dopamine-depleted caudate putamen of unilaterally 6-hydroxydopamine-lesioned rats. At 6 weeks, animals with functional, mature grafts (as assessed by amphetamine-amplified behavioural asymmetry), were pretreated with pargyline (75 mg/kg i.p.), and both striatal sides were monitored for dopamine overflow for 90 min following amphetamine sulphate administration (5 mg/kg i.p.). The time course of dopamine overflow inside the graft was similar to that in the contralateral caudate putamen of the same animal, the normal control animal and the contralateral caudate putamen of 6-hydroxydopamine-lesioned animals. However, in grafted animals the mean dopamine overflow detected in the contralateral caudate putamen was approximately 34% lower than the concentration of dopamine detected in the contralateral caudate putamen of 6-hydroxydopamine-lesioned control animals and approximately 39% lower than the concentration of dopamine detected in the caudate putamen of the normal control animal. There was no statistical difference in the concentration of amphetamine-induced dopamine overflow between the caudate putamen contralateral to the 6-hydroxydopamine lesion and the caudate putamen of the normal control animal. These data suggest that intrastriatal foetal ventral mesencephalic suspension grafts reduce amphetamine-induced dopamine release in the contralateral non-grafted caudate putamen.
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  • 118
    ISSN: 1432-1106
    Schlagwort(e): Trigeminal nerve ; Primary afferents ; Synapses ; Ultrastructure ; Vibrissae ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Neonatal transection of the infraorbital nerve (ION; the trigeminal, V, branch that supplies the mystacial vibrissae follicles) results in an upregulation of galanin in the central arbors of primary afferent axons. The present study was undertaken to evaluate the synaptic organization of these galanin-positive primary afferents and compare it with that of normal neurobiotin/biocytin-labeled primary afferent axons from animals of the same age. Examination of 1200 neurobiotin/biocytin-labeled profiles in V nucleus principalis (PrV) of rats killed on postnatal day (P-) 7 indicated that 23.3% (n=279) of these profiles made synaptic contacts: 87.4% were axodendritic, 8.9% were axoaxonic, 2.8% were axosomatic, and 0.7% were axospinous. Evaluation of 1200 galanin-positive profiles in PrV from rats that sustained transection of the ION on P-0 and were killed on P-7 indicated that only 64 (5.3%) of these profiles made synaptic contacts (P〈0.05 compared with the intact animals). Of the galanin-positive profiles that did make synapses in PrV, 81.2% (n=52) were axodendritic and 18.8% (n=12) were axoaxonic. These results indicate that galanin released by damaged ION primary afferents in PrV is likely to affect the activity of second-order V neurons by a paracrine action rather than by acting at specific synapses.
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  • 119
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 110 (1996), S. 15-20 
    ISSN: 1432-1106
    Schlagwort(e): Calcium current ; Cerebellar granule neuron ; Heloderma ; Helodermine ; Ion channel block ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Helothermine (HLTx), a 25.5-kDa peptide toxin isolated from the venom of the Mexican beaded lizard (Heloderma horridum horridum), was found to be an inhibitor of Ca2+ channels in cerebellar granule cells of newborn rats. Macroscopic currents, carried by 10 mM Ba2+, were measured in whole-cell configuration. The toxin at the saturating dose of 2.5 μM reversibly produced an ≈67% block of the voltage-dependent Ca2+ current by a fast mechanism of action. The current inhibition and recovery were reached in less than 1 min. Inhibition was concentration-dependent, with a half-effective dose of 0.25 μM. The current block was practically voltage-independent, whereas the steady-state inactivation h ∞ was significantly affected by HLTx (≈10 mV). The toxin did not affect the activation and inactivation kinetics of the Ca2+ current. Experiments with other Ca2+ channel blockers showed that HLTx abolished ω-conotoxin GVIA-sensitive Ca2+ currents, as well as ω-AgaIVA- and dihydropyridine-sensitive Ca2+ currents. These drugs had virtually no effect when HLTx was applied first. The present results indicate that HLTx produce a high-potency blockage of the three pharmacologically distinct Ca2+ current components.
    Materialart: Digitale Medien
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  • 120
    ISSN: 1432-1106
    Schlagwort(e): Intracortical microstimulation ; c-fos ; Ca2+/calmodulin-dependent protein kinase II ; Glutamic acid decarboxylase ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Long-train tetanic stimulation of the cerebral cortex induces long-term changes in the excitability of cortical neurons, while short-train electrical stimulation does not. In the present study, we show that both forms of stimulation when applied to rat motor cortex for 4 h enhance c-fos expression, but only tetanic stimulation, when imposed upon short-train stimulation, modulates gene expression for 67-kDa glutamic acid decarboxylase (GAD) and alpha Ca2+/calmodulin-dependent protein kinase II (CaMKIIα). Gene expression for beta Ca2+/calmodulin-dependent protein kinase II is not affected by either stimulation mode. GAD messenger RNA (mRNA) is increased from 1 h after the end of tetanization to the longest poststimulus survival time investigated (14 h). CaMKIIα mRNA is decreased 1–3 h after the end of tetanization but thereafter returns to prestimulus levels. These results imply not only that mechanisms underlying neocortical plasticity are stimulus-dependent but also that they involve reciprocal changes in molecules regulating the balance of excitation and inhibition.
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  • 121
    ISSN: 1432-1106
    Schlagwort(e): Neural transplantation ; Parkinson's disease ; Tissue cultures ; Mesencephalon ; Human embryo ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Free-floating roller tube cultures of human fetal (embryonic age 6–10 weeks post-conception) and rat fetal (embryonic day 13) ventral mesencephalon were prepared. After 7–15 days in vitro, the mesencephalic tissue cultures were transplanted into the striatum of adult rats that had received unilateral injections of 6-hydroxydopamine into the nigrostriatal bundle 3–5 weeks prior to transplantation. Graft survival was assessed in tyrosine hydroxylase (TH)-immunostained serial sections of the grafted brains up to post-transplantation week 4 for the human fetal xenografts and post-transplantation week 11 for the rat fetal allografts. d-amphetamine-induced rotation was monitored up to 10 weeks after transplantation in the allografted animals and compared with that of lesioned-only control animals. All transplanted animals showed large, viable grafts containing TH-immunoreactive (ir) neurons. The density of TH-ir neurons in the human fetal xenografts and in rat fetal allografts was similar. A significant amelioration of the amphetamine-induced rotation was observed in the animals that received cultured tissue allografts. These results promote the feasibility of in vitro maintenance of fetal human and rat nigral tissue prior to transplantation using the free-floating roller tube technique.
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  • 122
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 110 (1996), S. 347-359 
    ISSN: 1432-1106
    Schlagwort(e): Glutamate ; Aspartate ; Developing neocortex ; Immunocytochemistry ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The excitatory amino acids l-glutamate and l-aspartate are believed to be utilized as neurotransmitters by the pyramidal neurons in the mammalian cerebral cortex. These cells can be recognized early in development, while glutamate might play an important part in the maturation and plasticity of the cortex. Here, we used light and electron microscopic immunocytochemistry to study the time of appearance and maturation of glutamate and aspartate in neurons of the rat visual cortex. Glutamate- and aspartate-immunoreactive cells were first detected in deep cortical layers at postnatal day 3. During the next 3 weeks, labelled neurons were observed progressively in more superficial layers, but did not demonstrate their adult pattern of distribution until postnatal week 4. Electron microscopic analysis showed that glutamate- and aspartate-labelled neurons gradually develop their cytological and synaptic features during the first 4 postnatal weeks, with this process of differentiation originating in the deep cortical layers and progressively extending to the superficial layers. These findings suggest that cortical pyramidal neurons begin to express detectable levels of transmitter glutamate and/or aspartate after they have completed their migration. Their neurochemical differentiation follows an “inside-out” pattern similar to the pattern described for the genesis and morphological differentiation of this population of cortical neurons.
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  • 123
    Digitale Medien
    Digitale Medien
    Springer
    Experimental brain research 110 (1996), S. 425-434 
    ISSN: 1432-1106
    Schlagwort(e): Superior colliculus ; Turning ; Cerebellum ; Substantia nigra ; Basal ganglia ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In a recent electrophysiological experiment, we showed the deep cerebellar nuclei to be a major source of excitatory input to the superior colliculus. Furthermore, target neurons in the colliculus were found, in every case, to receive convergent tonic inhibitory input from the substantia nigra pars reticulata. In the present study, we investigated these effects in the awake rat. We asked whether circling behaviour, induced by unilateral injection of a GABA antagonist into the lateral colliculus, could be suppressed by concurrent cerebellar inactivation. Rats were chronically implanted with bilateral guide cannulae located above the superior colliculus and deep cerebellar nuclei. Bicuculline methiodide (25 pmol) was microinjected unilaterally into intermediate layers of the colliculus at increasing depths until an optimal contralateral circling response was elicited. This behaviour was taken as the “baseline response” and was the first of three treatments. The second was an identical manipulation of the colliculus with a concurrent 200-nl microinjection of 1 M GABA into the contralateral deep cerebellar nuclei. The third was a repeat of BIC alone into the colliculus or, if rotation had been suppressed by more than 50% on test 2, the treatment was collicular BIC plus deep cerebellar saline. This latter treatment was used as a control for possible non-pharmacological injection effects. The effect of cerebellar GABA at 26 sites (17 within cerebellar nuclei and 9 outside) on BIC-induced rotation at 15 collicular sites was studied in ten animals. Only GABA injections at sites that fell within the cerebellar nuclei significantly reduced turning (P〈0.0001). A full behavioural analysis showed that this was a specific suppression of turning, not the result of general motor impairment. These results provide clear behavioural evidence that opposing, convergent influences from the basal ganglia and cerebellum interact in the lateral superior colliculus to control head and body movements. They furthermore suggest that the tonic deep cerebellar excitation of the superior colliculus could be the driving force in the expression of rotation induced by manipulations of the basal ganglia.
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  • 124
    ISSN: 1432-1106
    Schlagwort(e): Cell death ; Neurotrophins ; Retrograde labeling ; Tyrosine hydroxylase ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Intraparenchymal injections of the neurotoxin 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle in rats destroys the dopaminergic neurons in the pars compacta of the substantia nigra. In other transmitter systems it has been found that axotomy or neurotoxin exposure produces an initial loss of neurotransmitter phenotype, with cell death occurring over a much slower time course. To determine whether this also occurs in dopamine neurons after 6-OHDA, two approaches were utilized. First, the effect of injections of 6-OHDA into the medial forebrain bundle on nigral dopaminergic neurons was studied using combined fluorogold and immunocytochemical labeling. Four weeks after the 6-OHDA injection, there was an 85% reduction in the number of tyrosine hydroxylase (TH)-immunoreactive cells on the lesioned side. In contrast, there was only a 50% reduction in the number of fluorogold-labeled cells on the lesioned side. Second, the time course of the rescue of dopaminergic neurons after 6-OHDA by glial cell line-derived neurotrophic factor (GDNF) was determined using TH immunocytochemistry. Greater numbers of dopamine neurons were rescued 9 weeks after GDNF, compared with counts made 5 weeks after GDNF. Taken together, these results suggest loss of dopaminergic phenotype is greater than cell loss following 6-OHDA injections, and that GDNF restores the phenotype of affected cells.
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  • 125
    ISSN: 1432-1106
    Schlagwort(e): Male sexual behavior ; Vasopressin ; Limbic system ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract During sexual behavior in the male rat, peptidergic cells in the medial amygdaloid nucleus become active and release a vasopressin-like peptide. The present experiments were designed to examine hippocampal changes as a result of this peptide's action during sexual behaviors. Chronic field-potential recordings from the hippocampus of male rats were acquired in a wide variety of social and nonsocial circumstances. Hippocampal responses that resemble the known action of the vasopressin-like peptide were seen only with social stimuli such as sexual stimuli and stimuli that led to aggressive behavior between males. The results show that the occasions of peptide action in the hippocampus correlate with the occasions of peptide release as determined by recording from the peptidergic cell bodies. The results are interpreted to indicate that the amygdala projection to the hippocampus has a special role to play in social behavior.
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  • 126
    ISSN: 1432-1106
    Schlagwort(e): Retrorubral field ; Hippocampal formation ; Mesolimbic dopaminergic system ; Phaseolus vulgaris leucoagglutinin ; Tyrosine hydroxylase immunohistochemistry ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The dopaminergic neurons in the midbrain of the rat are located in three groups: the ventral tegmental area (VTA-A10), substantia nigra (SN-A9), and retrorubral field (RRF-A8). We have recently examined the organization of the projections from the VTA and the SN to the hippocampal formation (HF) in the rat. In the present study we characterize the projections of the RRF to the HF by using anterograde tracing, retrograde tracers, and tyrosine hydroxylase (TH) immunohistochemistry. Following iontophoretical injections of Phaseolous vulgaris leucoagglutinin (PHA-L) into the RRF, anterograde labeling was observed primarily in the ipsilateral subiculum and adjacent CA1 cell field. Sparse labeling was also observed in the CA3 cell field and dentate gyrus. The distribution of RRF neurons projecting to the HF was examined by injecting retrograde fluorescent tracers (fluorogold, fast blue, and nuclear yellow) into several hippocampal areas. The retrograde tracer findings indicate that the medial aspects of the RRF project to the subiculum and adjacent CA1 cell field of both the septal and temporal HF. In order to evaluate the percentage of dopaminergic cells of the RRF projecting to the HF, the retrograde neuronal tracer fluorogold was used in combination with TH immunohistochemistry. The quantitative evaluation of retrograde labeled and TH-immunoreactive (IR) cells showed that RRF projections to the HF are partially (10–18%) dopaminergic. The findings suggest that the general pattern of distribution and organization of the RRF-A8 projections to the HF is similar to that observed in our previous studies examining hippocampal afferents from the VTA and SN. The data also suggest a crude topographical organization of RRF afferents to the HF and a more prominent input to the temporal than to the septal HF.
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  • 127
    ISSN: 1432-1106
    Schlagwort(e): Perinatal asphyxia ; Dopamine utilization ; Tyrosine hydroxylase activity ; Substantia nigra ; Neostriatum ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The present study was undertaken in order to study the effects of perinatal asphyxia on tyrosine hydroxylase (TH) activity, dopamine levels and turnover, and dopamine metabolites (3,4-dihydroxyphenylacetic acid, DOPAC, homovanillic acid, HVA, and 3-methoxytyramine, 3-MT, analyzed by high-performance liquid chromatography, HPLC) measured in the basal ganglia of the 20- to 40-min-old newborn and 4-week-old male rat. Asphyxia was induced in pups by placing the fetuses, still in their uterus horns removed by hysterectomy from pregnant rats at full term, in a 37°C water bath for 15–16 min or 19–20 min. Following asphyxia, the uterus horns were opened, and the pups were removed and stimulated to breathe. A 100% and 50–80% pup survival was obtained following 15–16 min and 19–20 min of asphyxia, respectively. Acute changes were studied in brains from newborn pups 20–40 min after delivery, and long-term changes were studied in brains from 4-week-old rats. No changes in TH-activity could be observed in the substantia nigra/ventral tegmental area (SN/VTA), the striatum, or the accumbens nucleus/olfactory tubercle (ACC/TUB), in the newborn or the 4-week-old rat. In the newborn rat, 19–20 min of asphyxia increased (as compared to controls) dopamine levels in the SN/VTA to 136±14% and in the ACC/TUB to 160±10%, indicating an increased synthesis and/or release of dopamine. DOPAC levels were increased in the SN/VTA to 150±14% and in the ACC/TUB to 151±10%, and HVA levels were increased to 152±16% in the striatum and to 117±4% in the ACC/TUB. Following 15–16 min of asphyxia, dopamine levels were increased to 130±12% in the ACC/TUB, and DOPAC levels were increased to 135±6% and 130±12% in the SN/VTA and the ACC/TUB, respectively. This suggests that the increased dopamine levels may preferably reflect an increased release of dopamine following perinatal asphyxia. In the 4-week-old rat, dopamine levels were decreased in the SN/VTA to 71±4%, in the striatum to 52±8%, and in the ACC/TUB to 53±7%, following 19–20 min of perinatal asphyxia as compared to controls. No changes were observed in DOPAC, HVA, or 3-MT levels, indicating that the reduced dopamine levels reflect a reduced dopamine synthesis following perinatal asphyxia. A decrease in dopamine utilization was observed in the striatum to 15±8% and in the ACC/TUB to 9±13% following 19–20 min of perinatal asphyxia as compared to controls. This indicates that perinatal asphyxia produced long-lasting reductions in activity in the mesostriatal/mesolimbic dopamine systems in the 4-week-old rat.
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  • 128
    ISSN: 1432-0738
    Schlagwort(e): Key words L-2-Chloropropionic acid ; Glutathione ; Cerebellar granule cell necrosis ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The role of glutathione (GSH) in the neurotoxicity produced following a single oral dose of 750 mg/kg L-2-chloropropionic acid (L-CPA) has been investigated in rats. L-CPA-induced neurotoxicity was characterised by up to 80–90% loss in cerebellar granule cells and cerebellar oedema leading to locomotor dysfunction. Neurochemically, L-CPA-induced neurotoxicity produced a reduction in the concentration of aspartate and glutamate in the cerebellum and a reduction in the density of NMDA receptors in the cerebellar cortex, whilst there was an increase in cerebellar glycine, glutamine and GABA concentrations. Treatment of rats with buthionine sulfoximine (BSO) at 1 g/kg, i.p., an inhibitor of GSH synthesis, potentiated the toxicity of L-CPA, such that many of the neurochemical markers were significantly different from controls at earlier time points, compared to animals which had received L-CPA alone, and toxicity was also seen in the kidney of BSO plus L-CPA treated rats. In contrast, supplementing GSH concentrations by administration of the isopropyl ester of glutathione (ip-GSH) at 1 g/kg, s.c., was able to protect rats against L-CPA neurotoxicity and prevent many of the neurochemical changes. In order to assess whether the depletion of GSH in the rat cerebellum following L-CPA treatment was related to the delivery of cysteine or cystine, the accumulation of [14C] cystine into cerebellar slices was characterised and found to be energy dependent, Na+ independent and obey saturation kinetics with an apparent Km of 77 μM and an apparent Vmax of 450 nmol/g wet weight per h. The accumulation of cystine into cerebellar slices was non-competitively inhibited by the cysteine conjugate of L-CPA with an apparent Ki of approximately 60 μM, whilst glutamate only inhibited cystine accumulation at doses which were cytotoxic to cerebellar slices. Hence the depletion of GSH in the rat cerebellum, following L-CPA administration, may be due to a reduction in the delivery to the brain of cysteine or cystine, one of the components required for GSH synthesis, by the cysteine conjugate of L-CPA. Our studies show the pivotal role GSH plays in cerebellar granule cell necrosis induced by L-CPA in the rat, indicating that a marked and sustained reduction in cerebellar GSH content by L-CPA may leave granule cells vulnerable to cytotoxic free radical damage leading to cell death, possibly mediated through excitatory amino acids.
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  • 129
    Digitale Medien
    Digitale Medien
    Springer
    Archives of toxicology 70 (1996), S. 474-481 
    ISSN: 1432-0738
    Schlagwort(e): Key words Quinolone (♪) ; Cartilage lesions ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The reversibility of quinolone-induced cartilage lesions has not been studied in detail. We treated five groups of five to seven juvenile Wistar rats (male and female; age: 5 weeks) with 2×600 mg ofloxacin/kg by gastric intubation on 1 day only (9:00 a.m. and 5:00 p.m.) and studied the knee joints histologically 3 days, 1, 3, 8 and 17 weeks later. In addition, joint cartilage specimens from vehicle-treated control rats (n=21) at corresponding age were examined. Cartilage lesions such as matrix swelling, loss of proteoglycans and horizontal clefts were found in nearly all knee joints (26 of 27 joints; incidence: 96%) of the ofloxacin-treated rats. Within the observation period of 4 months the size of these lesions in knee joint cartilage did not decrease significantly. The diameter of the lesions at the time points of evaluation was 1146±535, 1713±309, 1250 ±585, 1406±356, and 1542±467 μm, respectively (mean values±sd). Chondrocyte clusters producing glycosaminoglycans were observed 3 weeks after dosing and at later time points. They are considered to reflect the onset of repair but chondrocyte organization did not normalize during the study period, thus indicating the irreversibility of the effect under the experimental conditions. In principle, long-term joint cartilage damage has to be taken into account when the use of quinolones in children is considered. More detailed pharmacokinetic data are necessary for a reasonable risk assessment approach.
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  • 130
    ISSN: 1432-0738
    Schlagwort(e): Key words Cadmium ; Erythropoietin ; Anemia ; Rat ; Kidney
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Cadmium (Cd), a highly toxic heavy metal, is distributed widely in the general environment of today. The characteristic clinical manifestations of chronic Cd intoxication include renal proximal tubular dysfunction, general osteomalacia with severe pains, and anemia. We have recently reported that the serum level of erythropoietin (EPO) remained low despite the severe anemia in patients with Itai-itai disease, the most severe form of chronic Cd intoxication. In order to prove that the anemia observed in chronic Cd intoxication arises from low production of EPO in the kidneys following the renal injury, we administered Cd to rats for a long period and performed the analysis of EPO mRNA inducibility in the kidneys. The rats administered Cd for 6 and 9 months showed anemia with low levels of plasma EPO as well as biochemical and histological renal tubular damage, and also hypoinduction of EPO mRNA in the kidneys. The results indicate that chronic Cd intoxication causes anemia by disturbing the EPO-production capacity of renal cells.
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  • 131
    Digitale Medien
    Digitale Medien
    Springer
    Archives of toxicology 70 (1996), S. 174-181 
    ISSN: 1432-0738
    Schlagwort(e): Key words Hexachlorobenzene ; Rat ; Operant behavior ; Gestation ; Liver
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Hexachlorobenzene (HCB) is still frequently found at elevated levels in human adipose tissue and breast milk. As intoxication with HCB causes neurological disturbance in human beings, the purpose of the present study was to examine neurobehavioral functions in rats after pre- and postnatal exposure. Female rats were fed diets with 0, 4, 8, or 16 mg HCB/kg diet. Exposure started 90 days prior to mating and was continued throughout mating, gestation, and lactation. Thereafter, the offspring were given the same diets as their respective mothers. HCB levels were determined in the brain, the liver, and in the adipose tissue from virgin rats, dams, and the offspring. Concentrations on a lipid basis were found to decline in the order adipose〉liver〉brain. The exposure levels chosen did not cause gross toxic effects in dams or offspring. There were dose-related increases in liver-to-body-weight ratios in exposed dams, but not in unmated females treated alike. Behavioral testing was conducted in the offspring. Examination of open-field activity on PND 21, and of active avoidance learning on PND 90 failed to reveal significant differences between groups. Training of operant behavior started at the age of 150 days in the offspring from the control, the 8-mg group, and the 16-mg group. Animals were trained on a fixed interval schedule of 1 min (FI-1). On this schedule, responses were reinforced by a food pellet every time 1 min had elapsed after the preceding reinforcement. There were dose-dependent reductions in the post-reinforcement pause, e.g. the time between each reinforcement and the first reaction emitted after it. In addition, the index of curvature, which describes the efficiency of performance on the FI-1 schedule, was decreased in a dose-dependent fashion.
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  • 132
    ISSN: 1432-0738
    Schlagwort(e): Key words Glutathione ; Glutathione-related enzymes ; Hepatocytes ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The effect of culture medium on glutathione (GSH) dependent detoxification defence system of primary cultured hepatocyte from either male or female rats was studied. Intracellular reduced (GSH) and oxidized glutathione (GSSG), and six GSH-related enzyme activities, including GSH peroxidase (GSH Px), GSH reductase (GSH Rd), cytosolic GSH S-transferase (cGST), microsomal GSH S-transferase (mGST), γ-glutamyl transpeptidase (GTP), and γ-glutamylcysteine synthetase (GCS), were investigated during a 6-day culture. Media free of fetal bovine serum (FBS) and with 2.5 or 10% FBS were used. Whatever the medium, there was an initial increase of intracellular GSH and GSSG, a threefold increase of GSH at day 3 and fourfold increase of GSSG at day 4, later decreasing to their original level at day 6. The activities of all six GSH-related enzymes of male and female hepatocytes remained relatively stable during the first 72 h, then gradually decreased to 50–80% of initial activities. With the exception of cGST, time-course profiles of other enzyme activities were not significantly different among various media. In both sexes, higher cGST activity was maintained for cells cultured in the presence of FBS. Results of immunoblotting analysis of cytosolic GST isozymes indicate that the placental form of GST (Yp) was markedly increased after plating and the extent of increase of Yp was higher in the presence of FBS. Despite the culture medium, the level of GST isoform Ya was maintained steadily for 6 days, however, Yb was maintained during the first 3 days and then decreased. In terms of the gender difference, GSH Px and GTP activities of hepatocytes from females were significantly greater than of males over the entire culture period. Results indicate that FBS seems not to be absolutely essential in maintaining GSH level and most of the GSH-related enzyme activities in rat hepatocytes. Furthermore, GSH levels and GSH-related enzyme activities of hepatocytes from female rats were similar to those from male rats.
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  • 133
    Digitale Medien
    Digitale Medien
    Springer
    Archives of toxicology 70 (1996), S. 310-314 
    ISSN: 1432-0738
    Schlagwort(e): Key words Methylmercury ; Mercury ; Placenta ; Neutral amino acid ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Methylmercury (MeHg) penetrates the placental barrier to affect developing fetuses in the uterus. However, the mechanism of placental MeHg transport is not well defined. To clarify the MeHg transport system that functions in the placenta, pregnant rats were intravenously administered MeHg on day 18 of gestation. The fetal blood was collected from the umbilical cord at 30 and 60 min after the administration, and its mercury concentration was measured. MeHg was found to be rapidly transported to the fetal blood in a time- and dose-dependent manner, and predominantly distributed in the blood cells there. MeHg transport was effectively suppressed by the co-injection of neutral amino acids, i.e., L-methionine and L-phenylalanine, suggesting that MeHg is actively transported as its cysteine conjugate via the neutral amino acid carrier system. The suppression by methionine was not so marked as by phenylalanine. Since methionine administration caused a rapid increase of the cysteine, which functioned as a predominant carrier in MeHg transport, in the maternal plasma, newly synthesized cysteine seemed to accelerate the mercury uptake. Accordingly, the acceleration by the extra cysteine would compensate partly the competitive effect of methionine as a neutral amino acid.
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  • 134
    Digitale Medien
    Digitale Medien
    Springer
    Archives of toxicology 70 (1996), S. 329-337 
    ISSN: 1432-0738
    Schlagwort(e): Key words Formaldehyde ; Acrolein ; Acetaldehyde ; Rat ; Sensory irritation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Sensory irritation of formaldehyde (FRM), acrolein (ACR) and acetaldehyde (ACE) as measured by the decrease in breathing frequency (DBF) was studied in male Wistar rats using nose-only exposure. Groups of four rats were exposed to each of the single compounds separately or to mixtures of FRM, ACR and/or ACE. Exposure concentrations of the mixtures were chosen in such a way that summation of the effects of each chemical would be expected not to exceed 80% reduction of the breathing frequency. FRM, ACR and ACE appeared to act as sensory irritants as defined by Alarie (1966, 1973). With FRM and ACR desensitization occurred, whereas with ACE the breathing frequency gradually decreased with increasing exposure time (up to 30 min). For mixtures, the observed DBF was more pronounced than the DBF for each compound separately, but was less than the sum of the DBFs for the single compounds. A model for three compounds competing for the same receptor was applied to predict the DBF of mixtures of FRM, ACE and ACR. The results also showed that with mixtures no desensitization occurred; in fact, the breathing frequency further decreased in the last 15 min of exposure. These observations were similar to those found for ACE alone, and might have been caused by effects on the upper respiratory tract. The results of the present study allow the conclusion that sensory irritation in rats exposed to mixtures of irritant aldehydes is more pronounced than that caused by each of the aldehydes separately, and that the DBF as a result of exposure to a mixture could well be predicted using a model for competitive agonism, thus providing evidence that the combined effect of these aldehydes is basically a result of competition for a common receptor (trigeminal nerve).
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  • 135
    Digitale Medien
    Digitale Medien
    Springer
    Archives of toxicology 70 (1996), S. 368-372 
    ISSN: 1432-0738
    Schlagwort(e): Key words Phenobarbital ; 2-Aminoisobutyric acid ; Hepatoytes ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Phenobarbital (PB) is a classical inducer of drug metabolizing enzymes and known to stimulate liver growth transiently in rodents. Previous studies have shown that regenerative liver growth after a partial hepatectomy is accompanied by the induction of the amino acid transport system A. In the present study we investigated whether amino acid transport is also increased by treatment of rats with PB. Na+-dependent hepatic uptake of the non-metabolizable amino acid 2-aminoisobutyric acid (AIB), which proceeds largely via transport system A, was studied in isolated hepatocytes from PB treated and untreated rats. Uptake of AIB (100 μM) was maximally induced (2.5-fold) 8 h after the beginning of PB treatment. Within 4 days, transport rates decreased to values similar to those determined in hepatocytes from untreated animals, despite the continuation of PB treatment. In contrast, induction of the PB-inducible cytochromes P450 2B1/2 was markedly increased during the entire experiment, as determined with the isoenzyme-selective substrate pentoxyresorufin. Kinetic analysis of AIB uptake revealed a “high” and a “low” affinity transport system. It is most likely that the high affinity system represents amino acid transport system A. Treatment with PB increased the Vmax value but did not affect the apparent Km value of the high affinity system. The present data suggest that the hepatic mitogen PB transiently induces amino acid transport system A.
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  • 136
    Digitale Medien
    Digitale Medien
    Springer
    Surgical endoscopy and other interventional techniques 10 (1996), S. 490-494 
    ISSN: 1432-2218
    Schlagwort(e): Laparoscopy ; Rat ; Tumor take ; Weight loss ; Pneumoperitoneum ; Bowel resection
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Background: The ability of laparoscopic techniques to treat malignant disease is controversial. We developed a rat model to assess metabolic and oncological effects of laparoscopic surgery. Methods: Experiment I. The postoperative body weight in 10 rats having laparoscopic bowel resection (group I), 10 rats having open bowel resection (group II) and 5 rats having anesthesia only (group III) was determined. Experiment II. Tumor take was scored in 11 rats having laparoscopic bowel resection (group IV), 11 rats having open bowel resection (group V), 6 rats having CO2 pneumoperitoneum without bowel resection (group VI) and 6 rats having anesthesia only (group VII). All rats had CC531 cancer cells injected intraperitoneally postoperatively. Results: Experiment I. Body weight loss in group I compared to group II (p〈0.036). Rats of group III lost no weight postoperatively. Experiment II. Tumor take was less in the subcutis (p=0.005), parietal peritoenum (p〈0.001) and bowel anastomosis (p=0.021) in group IV compared to group V. Tumor take was significantly greater at all sites except for subcutis in group VI compared to VII (all p〈0.022). Conclusions: Laparoscopic surgery is associated with less postoperative weight loss and less tumor take compared to open surgery. CO2 insufflation appears to increase tumor take.
    Materialart: Digitale Medien
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  • 137
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 123 (1996), S. 98-102 
    ISSN: 1432-2072
    Schlagwort(e): Sucrose ; Raclopride ; 5-HT2 antagonism ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We examined the effects on sucrose consumption of a dopamine (DA) D2/D3 antagonist (raclopride, 0–0.3 mg/kg), a serotonin 5-HT2/2c antagonist (ritanserin, 0–0.4 mg/kg), and raclopride (0.15 mg/kg) combined with ritanserin (0–0.4 mg/kg). Three different concentrations of sucrose solution (0.7%, 7.0% and 34%) were tested. The concentration-intake function in drug-free rats was an inverted-U, with 7.0% sucrose supporting the highest intake. Raclopride (0.3 mg/kg) inhibited intake of 7.0% sucrose, but its effect on 0.7% sucrose fell short of significance (P〈0.06) and intake of 34% sucrose was unchanged. Ritanserin did not affect sucrose intake when given on its own, but synergized with a previously ineffective dose of raclopride (0.15 mg/kg) so as to cause a significant inhibition of 7.0% sucrose intake and increase in 34% sucrose intake. These data indicate that 5-HT2 antagonism potentiated the behavioural effects of raclopride and we speculate that this interaction might contribute to the efficacy of atypical neuroleptic drugs.
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  • 138
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 123 (1996), S. 267-279 
    ISSN: 1432-2072
    Schlagwort(e): 2,4-Dithiobiuret ; Rat ; Cognitive facilitation ; Motor impairment
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract 2,4-Dithiobiuret (DTB) is a sulfonated derivative of urea that is used as a reducing agent in chemical manufacture. Its low acute toxicity to rodents belies a peripherally mediated, delayed-onset muscle weakness which develops during repeated daily exposure. In experiment 1, a standard dose regimen of DTB (0.5 mg/kg per day IP for 5 days) was used to induce motor dysfunction as a way to dissociate peripheral and central influences on a test of cognitive and motor function in rats. Sixteen male rats were trained to perform a Delayed Matching-to-Position/Visual Discrimination (DMTP/VD) task which permits quantification of working memory (matching accuracy), reference memory (discrimination accuracy), and motor function (choice response latency and nosepoke inter-response time, IRT). The first dose of DTB significantly increased matching accuracy; during the following week, DTB reduced matching accuracy, increased choice response latency and nosepoke IRT, and reduced trial completion. Discrimination accuracy remained unaffected. Experiment 2 explored the effects of single administrations of DTB on DMTP/VD. Sixteen other trained rats were divided into two groups with equal matching accuracy. One group received DTB (0.5,1.0, and 2.0 mg/kg, IP) in separate injections at least 1 week apart; the other group received vehicle at the same times. Matching accuracy increased significantly in the treated rats and not in the controls following each dose of DTB. The magnitude of this increase was dose-dependent, and lasted from 1 to 8 weeks after each injection. Discrimination accuracy, response latency, nosepoke IRT and trial completion remained unaffected throughout the study. After DTB, matching accuracy was less easily disrupted by scopolamine (0.1–0.3 mg/kg, IP). However, DTB did not alter the rats' response to reducing the distance between the response levers, to reversal of the matching rule to a nonmatching rule, or to challenge with MK-801 (0.05–0.10 mg/kg, IP). These data indicate that acute DTB causes a long-lasting facilitation of working memory in rats in the absence of any of the indications of motor impairment which follow repeated, daily injections of the chemical.
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  • 139
    ISSN: 1432-2072
    Schlagwort(e): Key words Thyrotrophin-releasing hormone ; RX77368 ; Alzheimer’s disease ; AMPA ; Septal-hippocampal ; Working memory ; Delayed non-matching to position (DNMTP) ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The aim of the present study was to determine the effect of a thyrotrophin-releasing hormone (TRH) analogue, RX77368, on performance of a working memory test, using a delayed non-matching to position (DNMTP) procedure, in (RS)-α-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid (AMPA)-induced septal-hippocampal lesioned rats. Following a post-surgery recovery period, pretrained rats were tested once daily on DNMTP, 30 min post-administration of RX77368 (1.0 mg kg–1, IP) or saline. AMPA-induced lesions significantly reduced percent correct responses during the second week of testing. Comparison of percent correct responses between days 1 and 13 of testing showed that sham rats significantly improved DNMTP performance, whereas lesioned rats did not. RX77368 significantly reduced general locomotor activity in sham rats in activity boxes, but did not disrupt non-mnemonic measures, such as locomotion and motivation, in the DNMTP test. RX77368 increased percent correct responses in AMPA-lesioned rats on days 8–10 and 11–13. There was also a significant improvement in percent correct responses achieved between day 1 and 13 in RX77368-treated lesioned and sham rats. These results showed that: (i) septal-hippocampal lesioned rats did not improve over the testing period; and (ii) on test days when a significant impairment was present, RX77368 partially improved DNMTP performance.
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  • 140
    ISSN: 1432-2072
    Schlagwort(e): Key words Opioids ; Tolerance ; Neurotensin ; NMDA ; Conditioning ; MK-801 ; Morphine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Opiate tolerance involves both associative and non-associative changes. However, procedures designed to distinguish between these two processes have rarely been employed when investigating the physiological basis of such plasticity. The present experiments assessed some of the mechanisms contributing to both associative and non-associative decreases in morphine analgesic potency following repeated IV morphine administration (4 days, 5 mg/kg per day). For one group of rats, testing for morphine analgesia (tailflick) occurred in a context that had been repeatedly paired with morphine administration. Another group of rats, exposed equally to the testing context, handling procedures and morphine, was tested for morphine analgesia in a context that was specifically unpaired with prior drug. Although both of these groups showed a decrease in the drug effect following repeated administrations, those rats tested in the morphine-associated context were significantly more tolerant than the unpaired group. We evaluated the spinal cord involvement of NMDA receptors, as well as the peptide neurotensin in these two types of tolerance. NMDA receptors appeared to mediate non-associative changes in drug potency, as rats tested in either context were less tolerant when morphine administration was preceded with the non-competitive NMDA antagonist, MK-801 (2.5 and 5 nmol). Spinal neurotensin antagonism with [d-Trp11]neurotensin (3 pmol) selectively abolished associative tolerance. These findings provide information about the mechanisms of opiate tolerance and support the distinction between associative and non-associative processes underlying these changes.
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  • 141
    ISSN: 1432-2072
    Schlagwort(e): Alzheimers' disease ; α2-Adrenoceptor antagonists ; Acetylcholinesterase inhibitor ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The cholinergic hypothesis of Alzheimer's disease (AD) has strongly influenced research on learning and memory over the last decade. However, there has been limited success treating AD dementia with cholinomimetics. Furthermore, there are indications that other neurotransmitter systems affected by this disease may be involved in cognitive processes. Animal studies have suggested that norepinephrine and acetylcholine may interact in learning and memory. The current experiments investigate this interaction in a step-down passive avoidance paradigm after coadministration of acetylcholinesterase inhibitors and α2-adrenoceptor antagonists. Administration of acetylcholinesterase inhibitors heptylphysostigmine (0.625–5.0 mg/kg, IP), tacrine (2.5–10.0 mg/kg, PO), velnacrine (0.312–2.5 mg/kg, SC), and galanthamine (0.312–2.5 mg/kg, IP) each enhanced retention of a passive avoidance response at selected moderate doses administered 30–60 min prior to training. The α2-adrenoceptor antagonists idazoxan (0.312–2.5 mg/kg, IP), yohimbine (0.078–0.312 mg/kg, IP) and P86 7480 (0.156–0.625 mg/kg, IP) alone failed to enhance learning in this paradigm. Coadministration of a subthreshold dose of heptylphysostigmine (0.625 mg/kg, IP) with doses of idazoxan, yohimbine or P86 7480 enhanced passive avoidance learning. This synergistic interaction may represent effects of antagonism of presynaptic α2-adrenoceptor since coadministration of heptylphysostigmine and the selective postsynaptic α2-adrenoceptor antagonist SKF104856 did not result in enhanced learning. Taken together these data suggest noradrenergic activation through pre-synaptic α2-adrenoceptor blockade may potentiate cholinergic activity in the formation of a long-term memory trace. These observations may have implications for the treatment of AD with cholinergic and adrenergic agents.
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  • 142
    ISSN: 1432-2072
    Schlagwort(e): Social recognition ; Memory ; Rat ; Mouse ; Cannabimimetic ; Cannabinoid antagonist ; SR 141716 ; Ageing
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Social short-term memory in rodents is based on the recognition of a juvenile by an adult conspecific when the juvenile is presented on two successive occasions. Cannabimimetics are claimed to induce memory deficits in both humans and animals. In the brain, they mainly bind to CB1 receptors for which anandamide is a purported endogenous ligand. SR 141716, a specific antagonist of CB1 receptors, dose-dependently reverses biochemical and pharmacological effects of cannabimimetics. More particularly, it antagonizes the inhibition of hippocampal long-term potentiation induced by WIN 55,212-2 and anandamide, and it increases arousal when given alone. The present experiments study the ability of SR 141716 (from 0.03 to 3 mg/kg SC) to facilitate short-term olfactory memory in the social recognition test in rodents. SR 141716 improved social recognition in a long intertrial paradigm with a threshold dose of 0.1 mg/kg SC. At 1 mg/kg, it antagonized the memory disturbance elicited by retroactive inhibition. Scopolamine (0.06 mg/kg IP) partially reversed its memory-enhancing effect. Moreover, SR 141716 reduced memory deficit in aged rats (0.03–0.1 mg/kg) and mice (0.3–1 mg/kg). As SR 141716 is not known to exhibit any pharmacological activity which is not mediated by CB1 receptors, the results strongly support the concept that blockade of CB1 receptors plays an important role in consolidation of short-term memory in rodents and suggest there may be a role for an endogenous cannabinoid agonist tone (anandaminergic) in forgetting.
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  • 143
    ISSN: 1432-2072
    Schlagwort(e): SKF 38393 ; Quinpirole ; SCH 23390 ; l-Sulpiride ; Nucleus accumbens shell ; Nucleus accumbens core ; Turning behaviour ; Dopamine D1 and D2 receptors ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The goal of this study was to determine whether dopamine D2 and/or D1 receptors in the shell and the core of the nucleus accumbens of rats have a differential role in turning behaviour. Unilateral injection of a mixture of the dopamine D2 receptor agonist quinpirole (10 µg) and the dopamine D1 receptor agonist 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7, 8-diol (SKF 38393, 5 µg) into the shell of the nucleus accumbens produced contralateral turning, when doses which per se were ineffective were injected. This effect was far greater than that found after similar injections into the core of the nucleus accumbens. The effect elicited from the shell was significantly attenuated by prior administration of either the dopamine D2 receptor antagonistl-sulpiride (25 ng/0.5 µl) or the dopamine D1 receptor antagonist (8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol (SCH 23390, 0.5 µg/0.5 µl) into the same region. These data together with the fact thatl-sulpiride is known to be a valid tool to differentiate the involvement of distinct regions within the shell underlie the conclusion that dopamine D2 and D1 receptors in the shell, but not the core, of the nucleus accumbens play a critical role in the contralateral turning induced by unilateral injection of dopamine receptor agonists into this nucleus. The results are discussed in view of the known output pathways of the shell.
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  • 144
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 126 (1996), S. 286-292 
    ISSN: 1432-2072
    Schlagwort(e): Modafinil ; Ephedrine ; Cocaine ; Amphetamine ; Self-administration ; Drug discrimination ; Rhesus monkey ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Modafinil [(diphenyl-methyl)sulphinyl-2-acetamide] is a novel psychostimulant drug which is effective in the treatment of narcolepsy and idiopathic hypersomnia. It also has neuroprotective effects in animal models of striatal neuropathology. Although the cellular mechanisms of action of modafinil are poorly understood, it has been shown to have a profile of pharmacological effects that differs considerably from that of amphetamine-like stimulants. There is some evidence that modafinil has central α1-adrenergic agonist effects. In the present study modafinil was evaluated for cocaine-like discriminative stimulus effects in rats and for reinforcing effects in rhesus monkeys maintained on intravenous cocaine self-administration. Modafinil,l-ephedrine andd-amphetamine all produced dose dependent increases in cocaine-lever responding, with maximal levels of 67%, 82% and 100%, respectively. Modafinil produced full substitution in four out of the six rats tested while the highest levels of substitution were associated with substantial response rate decreasing effects. Little evidence was obtained that the discriminative stimulus effects of modafinil were produced by α1-adrenergic activation, based upon results of tests performed in combination with prazosin. In the self-administration procedure, modafinil andl-ephedrine functioned as reinforcers in rhesus monkeys. The reinforcing and discriminative stimulus effects of modafinil required very high doses: modafinil was over 200 times less potent thand-amphetamine and was also less potent thanl-ephedrine. These results show that modafinil has some cocaine-like discriminative stimulus effects and, like other abused stimulants, can serve as a reinforcer at high doses.
    Materialart: Digitale Medien
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  • 145
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 125 (1996), S. 89-91 
    ISSN: 1432-2072
    Schlagwort(e): Dorsal raphe nucleus ; Rat ; WAY-100635 ; 8-OH-DPAT ; Somatodendritic 5-HT1A receptors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In the rat shock-induced ultrasonic vocalization test, the anxiolytic effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) obtained after systemic (IP) and intracerebral injection into the dorsal raphe nucleus (DRN) were selectively abolished by pretreatment with the 5-HT1A receptor antagonist WAY-100635 [N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide trihydrochloride]. This blockade was demonstrated both after systemic and DRN application of WAY-100635. Therefore, it is concluded that the anxiolytic effects of 8-OH-DPAT are mediated by activation of somatodendritic 5-HT1A receptors.
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  • 146
    ISSN: 1432-2013
    Schlagwort(e): Central chemoreceptors ; Peripheral chemoreceptors ; Fos ; Rat ; Hypercapnia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Exposure to hypercapnia and electrical stimulation of the carotid sinus nerve (CSN) has been shown to induce c-fos expression in several brain stem regions including the nucleus tractus solitarius (NTS). To test whether the labeled neurons were activated directly by hypercapnia or secondarily via the carotid bodies (sinus nerve), adult rats were exposed to either air or 14–16% CO2 for 1 h. Experiments were done on eight groups: (1) exposure to air, (2) exposure to CO2, (3) chronic CSN denervation/CO2, (4) chronic unilateral CSN denervation/CO2, (5) chronic sham CSN denervation/CO2, (6) anesthetized/CO2, (7) anesthetized and acute vagotomy/CO2, and (8) premedicated with morphine, 10 mg s.c., 20 min before exposure to CO2. After exposure to CO2 or air the rats were anesthetized, perfused with 4% paraformaldehyde and the brains processed for immunohistochemical staining for c-fos protein using the PAP (i.e. peroxidase anti-peroxidase) technique. Labeled neurons in the area of the NTS in every second 50-μm section were counted and their position plotted using a microscope and camera lucida attachment. Rats exposed to CO2 had a significantly greater number of labeled neurons in the NTS than those exposed to air. Other interventions, such as CSN denervation, surgery, anesthesia, vagotomy or injection of morphine did not significantly affect the level of c-fos expression in rats exposed to hypercapnia, indicative of central stimulation rather than secondary peripheral input. These responsive neurons may be part of a widespread central chemoreceptive complex.
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  • 147
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 431 (1996), S. 882-887 
    ISSN: 1432-2013
    Schlagwort(e): Key words Contractile ; Staircase ; Calcium ; Rat ; Fast-twitch ; Fatigue
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Myosin light chain (P-LC) phosphorylation, which is thought to be the principle mechanism for twitch potentiation in skeletal muscle, is significantly decreased during staircase in fatigued muscle. Attenuated phosphorylation of P-LC could be due to either depressed Ca2+ transients in fatigue, or to some inhibitory influence of contractile activity on myosin light chain kinase (MLCK). Tetanic stimulation, which would presumably result in maximal activation of MLCK, could be used to evaluate these potential mechanisms. P-LC phosphorylation and twitch developed tension (DT) were assessed at 20 and 120 s following a tetanic contraction in either rested or fatigued rat gastrocnemius muscle in situ. P-LC phosphorylation was significantly lower in fatigued muscles (39.7 ± 3.2% vs 54.8 ± 3.5%, 20 s after a 2-s tetanic contraction), while posttetanic potentiation (PTP) was similar in fatigued (189.1 ± 6.5%) versus rested muscle (169.5 ± 2.6%). Tetanic DT was reduced following the fatigue protocol and, thus, the assumption that the MLCK system was fully activated by Ca2+ may not be valid. The potentiation-phosphorylation relationships were linear for both rested and fatigued muscles; however this relationship was shifted markedly leftward in fatigued muscles. It appears that during PTP, equivalent potentiation is attained with correspondingly lower levels of P-LC phosphorylation in fatigued muscle. This enhanced relative potentiation for a given level of phosphorylation could be expected if Ca2+ transients were attenuated in the fatigued muscle. However the results do not rule out the possibility that other factors contribute to potentiation under these circumstances.
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  • 148
    ISSN: 1432-2013
    Schlagwort(e): Key words Hypobaric hypoxia ; Physical training ; Skeletal muscle ; Muscle fibre type ; Fibre cross-sectional area ; Enzymes of energy metabolism ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Adaptations of skeletal muscle morphology and metabolic enzymes were studied after prolonged training in and exposure to hypobaric (740 –770 mbar) as well as normobaric conditions in rats performing treadmill running training for 10, 21 and 56 days. Animals sacrificed after 91 days served as recovery groups from training and hypobaric exposure for 56 days. The rats were divided into normobaric sedentary (NS) and training (NT) groups and hypobaric sedentary (HS) and training (HT) groups. The weights of extensor digitorum longus (EDL) and soleus (SOL) muscles increased significantly in the 56HS and the 56HT groups compared with the 56NS group, the increase being greatest in the 56HS group. No differences in the mean fibre areas (MFA) of these muscles could be seen, whereas clearly reduced MFAs of type IIA and IIB were observed in the tibialis anterior (TA) muscle. However, fibre area distribution analyses in the EDL and TA muscles showed a higher proportion of larger fibers in the 56HS and 56HT groups than in the respective normobaric groups. On the contrary, in SOL muscles the proportion of smaller fibers was higher in the hypobaric than in normobaric groups at 56 days. Increased activities of citrate synthase and β-hydroxyacyl-CoA-dehydrogenase in SOL and TA muscles in the 56HT group indicate an increase in oxidative capacity. It is concluded that exposure to, and training in moderate hypobaric conditions leads to a positive muscle protein balance which is reflected in increased muscle weights. However, the sites of increased protein synthesis and the possible hyperplasia remain to be studied further.
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  • 149
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 432 (1996), S. 313-319 
    ISSN: 1432-2013
    Schlagwort(e): Key words Soleus muscle ; Rat ; Atrophy ; Unloading ; Motor units ; Contractile properties
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The purpose of this study was to compare the isometric contractile properties of rat soleus motor units after 14 days of hindlimb unloading (HU) to those under control conditions. The motor units (MU) were classified using two mechanical criteria: the presence or not of a sag during unfused tetani and the value of the twitch time-to-peak (TTP). Under control conditions, the soleus muscle was composed of 85% of slow-type (sag −, TTP 〉 20 ms) and 15% of fast-type (sag +, TTP 〈 20 ms) units. Following HU, these two populations were still present and results showed: (1) large decreases in their maximal tetanic tensions (of −67% and −60% for slow- and fast-type, respectively), and (2) changes in their relative proportions, i.e. a decrease in the percentage of slow-type units and a twofold increase in the percentage of fast-type units were observed. These latter changes might be the consequence of a complete transformation of slow-towards fast-type units. A third population appeared in the HU solei, 26% of the samples, combining the presence of a sag and speed-related properties between those of slow- and fast-type units. These slow-intermediate units might come from slow units partially transformed into a faster type during HU. Thus the present study showed that unloading conditions induced a reorganisation of the soleus motor unit profile. The complete or partial transformation of the motor units could be related to the changes in the electromyographical activity of the unloaded soleus.
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  • 150
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 431 (1996), S. 775-785 
    ISSN: 1432-2013
    Schlagwort(e): Rat ; Pancreas ; RIN cells ; Gap junctions ; Connexin43 ; Biophysical properties ; Voltage gating
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A communication-deficient cell line (RIN cells, derived from a rat islet tumour), stably transfected with cDNA coding for rat connexin43 (Cx43), was chosen to further assess the mechanism of voltage gating of Cx43 gap junction channels. The experiments were carried out on preformed cell pairs using a dual whole-cell, voltage-clamp method. The junctional current,I j, revealed a time- and voltage-dependent inactivation at transjunctional voltagesV j 〉 ± 40mV When an asymmetrical pulse protocol was used (in cell 1 the holding potential was maintained, in cell 2 it was altered to establish a variableV j), the channels exhibited an asymmetrical gating behaviour:V j,O = −73.7 mV and 65.1 mV for negative and positiveV j, respectively (V j at whichI j is half-maximally inactivated); gj(min) = 0.34 and 0.29 (normalized minimal conductance); τ = 350 ms and 80 ms atV j = 100 mV (time constant ofI j inactivation). Hence, these parameters were more sensitive to positiveV j values. When a symmetrical pulse protocol was used (the holding potentials in cell 1 and cell 2 were altered simultaneously in steps of equal amplitude but of opposite polarity), theV j —dependent asymmetries were absent:V j,O = −60.5 and 59.5; gj (min) = 0.27 and 0.29; τ = 64 ms and 47 ms at 100 mV Putative explanations for these obervations are discussed. A possibility is that the number of channels alters with the polarity ofV j.
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  • 151
    ISSN: 1432-2013
    Schlagwort(e): Key words Central chemoreceptors ; Peripheral chemoreceptors ; Fos ; Rat ; Hypercapnia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Exposure to hypercapnia and electrical stimulation of the carotid sinus nerve (CSN) has been shown to induce c-fos expression in several brain stem regions including the nucleus tractus solitarius (NTS). To test whether the labeled neurons were activated directly by hypercapnia or secondarily via the carotid bodies (sinus nerve), adult rats were exposed to either air or 14–16% CO2 for 1 h. Experiments were done on eight groups: (1) exposure to air, (2) exposure to CO2, (3) chronic CSN denervation/CO2, (4) chronic unilateral CSN denervation/CO2, (5) chronic sham CSN denervation/CO2, (6) anesthetized/CO2, (7) anesthetized and acute vagotomy/CO2, and (8) premedicated with morphine, 10 mg s.c., 20 min before exposure to CO2. After exposure to CO2 or air the rats were anesthetized, perfused with 4% paraformaldehyde and the brains processed for immunohistochemical staining for c-fos protein using the PAP (i.e. peroxidase anti-peroxidase) technique. Labeled neurons in the area of the NTS in every second 50-μm section were counted and their position plotted using a microscope and camera lucida attachment. Rats exposed to CO2 had a significantly greater number of labeled neurons in the NTS than those exposed to air. Other interventions, such as CSN denervation, surgery, anesthesia, vagotomy or injection of morphine did not significantly affect the level of c-fos expression in rats exposed to hypercapnia, indicative of central stimulation rather than secondary peripheral input. These responsive neurons may be part of a widespread central chemoreceptive complex.
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  • 152
    ISSN: 1432-2013
    Schlagwort(e): Nerve graft ; Magnification ; Motor nerve conduction velocity ; Compound muscle action potential ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Controversy surrounds the value of optic magnification for peripheral nerve surgery. The aim of this study was to compare the loupe magnification with microscope-assisted techniques in a rat tibial nerve graft model. The parameters studied included motor nerve conduction velocity (MNCV), clinical test equivalent (CTE), soleus muscle weight (SMW) and morphometric nerve indices. In the loupe and microscope groups MNCV mean was 26.77 ± 9.37 m/sec and 44.19 ± 11.36 m/sec respectively. MNCV results suggest better regeneration in the microscope group, as confirmed by CTE, SMW and myelinated fibre (MF) diameter.
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  • 153
    Digitale Medien
    Digitale Medien
    Springer
    Pflügers Archiv 433 (1996), S. 166-173 
    ISSN: 1432-2013
    Schlagwort(e): Key words Action potential ; Fatigue ; Ischaemia ; Muscle fibres ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  The proximal and distal compartments of rat medial gastrocnemius muscle are dominated, respectively by, fast-twitch oxidative and fast twitch glycolytic fibres. In the present study it was hypothesized that repetitive in situ activation with an intact blood supply would cause greater declines in maximal tetanic force, compound action potential (CAP) amplitude and CAP area in the distal compared to the proximal compartment. Furthermore, it was hypothesized that these differences would be eliminated after occlusion of the blood supply to the muscle. A twitch followed by a tetanus (120 Hz, 200 ms duration) was given every 3 s for 2 min. This exercise protocol was applied once with, and once without, blood supply. During the first minute of the exercise, as expected, occlusion enhanced the decline of proximal force to 77.4 ± 0.8%, a level comparable (P〉0.05) to the decline of distal force (79.7 ± 1.2%). In contrast with the hypothesis, CAP amplitude was not significantly affected by occlusion and it changed significantly less in the proximal (to 102.9 ± 4.5%) compared to the distal (to 69.0 ± 6.7%) compartment. During the second minute of activation without blood flow, sudden declines of distal CAP amplitude (to 18.4 ± 3.4%) coupled with parallel declines in force (to 17.6 ± 2.8%) were observed to occur in the distal but not in the proximal compartment. Proximal final force and CAP amplitude were 54.2 ± 2.6% and 80.6 ± 5.9% respectively. Thus, in contrast with the hypothesis, occlusion enhanced the differences between compartments. These results are discussed in relation to fibre type composition and metabolic changes. It is suggested that a loss of force caused by a decreased muscle fibre excitability upon repetitive activation depends not only on fibre type, but also on the intramuscular location of the fibres.
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  • 154
    ISSN: 1432-2072
    Schlagwort(e): Nicotine ; Lobeline ; Stimulus discrimination task ; Cognition ; Memory ; Cholinergic ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract This study evaluated the effects of two central nicotinic-cholinergic receptor agonists and an antagonist on performance accuracy of a rat, delayed stimulus discrimination task (DSDT). Rats were trained to discriminate between an auditory and visual stimulus by pressing a right or left lever. To diminish the rat's ability to use mediating spatial strategies to solve the task, computer automated, retractable doors separated the animal from the levers during delay intervals, thus reducing positioning at the lever. After stable baselines were achieved, rats were grouped and administered placebo (saline) and nicotine, lobeline or mecamylamine in a randomized dose series. Each group received two complete series of the selected compound on different occasions. Mecamylamine impaired DSDT accuracy in a dose-dependent manner while optimal doses of nicotine and lobeline significantly improved accuracy. Nicotine differed from lobeline in regard to its interaction with a dose of mecamylamine (1.0 mg/kg) that had not impaired DSDT accuracy. Combined administration of lobeline and mecamylamine was followed by a significantly increased level of DSDT accuracy that was similar to the improvement following administration of lobeline alone. In contrast, combined administration of nicotine and mecamylamine did not result in increased DSDT accuracy. Furthermore, lobeline administration similarly improved accuracy of trials associated with both the light and the tone, while nicotine improved accuracy of trials associated with the light to a much greater degree. These data suggest that the increases in DSDT accuracy associated with lobeline may be expressed through non-nicotinic mechanisms or a nicotinic receptor which is not blocked by mecamylamine.
    Materialart: Digitale Medien
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  • 155
    ISSN: 1432-2072
    Schlagwort(e): Amperozide ; FG5803 ; Haloperidol ; Antipsychotics ; Oral movements ; Chronic administration ; Acute administration ; Acute dystonia ; Tardive dyskinesia ; Extrapyramidal side effects ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Long-term studies of antipsychotic-induced oral movements may serve as a rat model of acute and tardive movement disorders. Vacuous chewing movements (VCM), tongue protrusions (TP), and jaw tremors (TR) were studied in rats during acute and chronic administration of two potential antipsychotics, amperozide and FG5803. Comparisons were made with haloperidol and vehicle. Single intraperitoneal injections of amperozide (0.2, 1, or 5 mg/kg) or FG5803 (1.2, 6, or 30 mg/kg) were without effect on oral behaviors. During long-term drug administration, withdrawal and readministration, endpoint analysis was focused on changes in supranormal oral movements. The maximal mean control frequencies found at 29 sessions during 14 months experiment +2 standard deviations were used to define the upper limit of the normal range. FG5803 (1.2, 6, or 30 mg/kg per day) administered via the drinking water for 12 months, did not produce significant deviations from this normal range with respect to VCM, TP, or TR, and this drug was not studied further. Rats receiving amperozide (0.2, 1, or 5 mg/kg per day) showed dose-related increases in oral movements over the year. The changes began after 3 months of treatment with amperozide 1 and 5 mg/kg per day, but became statistically significant only during the second half of the treatment year. Amperozide 0.2 mg/kg per day did not produce significant changes in oral movements during administration for a year, but drug withdrawal resulted in a significant rise in TP behavior. Haloperidol (1 mg/kg per day) produced increases in supranormal oral movements which tended to level out after 9 months. In all groups with significant elevations (i.e. haloperidol and amperozide 1 and 5 mg/kg per day), there was a persistence of such movements during a month of drug withdrawal. During treatment with amperozide (1 or 5 mg/kg per day), some rats developed a high frequency chewing behavior up to 175 VCMs/min. It is concluded that long-term treatment with amperozide, but not FG5803, produced a tardive pattern of supranormal oral movements. The importance of these findings for the clinical future of amperozide is difficult to predict, due to the unexpected finding of high-frequency chewing, which has not been noticed before during extensive studies of classical neuroleptics.
    Materialart: Digitale Medien
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  • 156
    ISSN: 1432-2072
    Schlagwort(e): 7-OH-DPAT ; Apomorphine ; Dopamine ; D3 receptors ; Locomotor activity ; Progressive-ratio ; Quinpirole ; Rat ; Self-stimulation ; Stereotypies
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract This study assessed the effects of IP injections of (±) 7-hydroxy-2(N,N-di-n-propylamino)tetralin (7-OH-DPAT), a dopamine agonist that has been reported to have preferential affinity for the dopamine D3 subtype of receptor, on four behavioural procedures in the rat: 1) spontaneous locomotion, 2) electrical self-stimulation of the ventral tegmental area (VTA), using the curve-shift procedure 3) operant responding for food under a progressive-ratio (PR) schedule and 4) induction of stereotypies. The effects of (±) 7-OH-DPAT were compared to the effects of apomorphine, a non-specific DA agonist, and quinpirole, a selective D2/D3 agonist. All three dopamine agonists decreased locomotor activity at low doses (0.01–0.3 mg/kg), and only apomorphine had clear locomotor stimulant effects at the highest dose tested (3 mg/kg). The three drugs dose-dependently depressed VTA self-stimulation in a similar way, with low doses inducing a fairly parallel rightward shift of the frequency/rate curves and higher doses flattening the curves. In contrast, responding for food under the PR schedule appeared to be differentially affected by the three agonists: 7-OH-DPAT induced a biphasic effect, with a maximal decrease in lever-pressing at 0.1 mg/kg, followed by a return to baseline levels with increasing doses (0.3–3 mg/kg); quinpirole showed a tendency to decrease responding over the whole dose-range tested with a maximal effect of about 50% of baseline between 0.25 and 1 mg/kg, and apomorphine dose-dependently decreased responding, with rats ceasing to respond at 0.3 mg/kg. All three DA agonists induced stereotypies, but there was a difference in the maximal stereotypy score induced by each of the ligands: 7-OH-DPAT produced a lower maximal effect than quinpirole or apomorphine. This indicates that each of the three dopamine agonists preferentially induced different types of stereotypies. Together, these data suggest that the putative dopamine D3 agonist 7-OH-DPAT, at low doses, has depressant effects similar to those induced by low doses of the other two DA agonists. Differences in the behavioural effects of higher doses were, however, mostly observed in two procedures, PR responding and induction of stereotypies.
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  • 157
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 125 (1996), S. 168-175 
    ISSN: 1432-2072
    Schlagwort(e): d-Fenfluramine ; Metergoline ; 8-OH-DPAT ; WAY-100635 ; Anorexia ; Satiety sequence ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract These studies investigated the involvement of the 5-HT1A receptor in mediatingd-fenfluramine-induced anorexia in the rat. Non-deprived,d-fenfluramine-treated (3.0 mg/kg) rats consumed a reduced amount of a palatable wet mash and showed a temporal advance in the behavioural sequence consistent with satiety. Thus, rats treated withd-fenfluramine ceased feeding and began resting before corresponding controls. Pretreatment with the selective 5-HT1A receptor antagonist WAY-100635 (1.0 mg/kg) had no effect on either the reduced mash consumption or behavioural satiety sequence ofd-fenfluramine-treated animals at a dose which was found to attenuate the anorexia induced by the 5-HT1A receptor agonist 8-OH-DPAT (0.5 mg/kg). Pretreatment with the nonselective 5-HT antagonist metergoline (1.0 mg/kg) attenuated thed-fenfluramine-induced reduction of mash consumption and the advanced offset of feeding. Metergoline pretreatment had no effect on the advanced onset of resting observed ind-fenfluramine-treated animals. These data suggest thatd-fenfluramine reduces food intake, perhaps by enhancing satiety, via a mechanism which does not involve the 5-HT1A receptor subtype. The implications of these results to the utility of the behavioural satiety sequence as a measure of postprandial satiety are discussed.
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  • 158
    ISSN: 1432-0878
    Schlagwort(e): Key words: Growth factors ; Brain-derived neurotrophic factor ; Immediate-early genes ; Tyrosine hydroxylase ; Glia ; Cell culture ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract. Glial cell line-derived neurotrophic factor (GDNF) is a highly selective neurotrophic factor for midbrain dopaminergic neurons and might thus be of potential use in the therapy of Parkinson’s disease. In this study, we present evidence that the survival-promoting action of GDNF on dopaminergic neurons requires the concurrent activation of cAMP-dependent signaling pathways. In serum-free low density cultures of the dissociated embryonic day 15 mesencephalon, dopaminergic neurons undergo constant cell death as evidenced by a 90% reduction in tyrosine hydroxylase-immunoreactive (TH-IR) cell numbers between days 1 and 9 of cultivation. This decline was not affected by GDNF (5 ng/ml) within the initial 3 days of cultivation, but was in part attenuated with prolonged treatment. In contrast, stimulation of 3-day-old mesencephalic cultures with GDNF induced c-fos expression in 73% of all TH-IR neurons, indicative for the early presence of efficient signal-transduction coupling in these neurons. Combined treatment of mesencephalic cultures with dibutyryl cyclic AMP (dbcAMP; 100 μM) and GDNF accelerated the onset of the survival effects of GDNF on dopaminergic neurons, resulting in a 1.5-fold increase in the number of surviving TH-IR neurons at 3 days in vitro. In addition, activation of cAMP-dependent signal pathways significantly potentiated the survival-promoting effects of GDNF on dopaminergic neurons in older cultures. dbcAMP alone had no effect on dopaminergic cell survival. Taken together, our findings suggest that the action of GDNF on midbrain dopaminergic neurons is modulated by other extracellular signals.
    Materialart: Digitale Medien
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  • 159
    Digitale Medien
    Digitale Medien
    Springer
    Cell & tissue research 286 (1996), S. 249-255 
    ISSN: 1432-0878
    Schlagwort(e): Key words: GDNF ; NT-4/5 ; Tachykinin ; Dopamine ; Amphetamine ; PPT-A ; Survival ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract. Glial-cell-line-derived neurotrophic factor (GDNF) is a novel trophic factor with potent trophic effects on several neuron populations in the central and peripheral nervous system. In the present study, we have investigated and compared the potential of dopamine and metamphetamine with that of the two striatal neurotrophic factors, viz., GDNF and neurotrophin-(NT)-4/5, to regulate substance P and its preprotachykinin-A mRNA in organotypic striatal slices from postnatal (day 10) rats. Incubation for 2 weeks with 10 ng/ml GDNF significantly increased substance-P-like immunoreactivity determined by radioimmunoassay. Similarly, the corresponding preprotachykinin-A mRNA increased after 1 and 2 weeks of incubation, as analyzed by in situ hybridization. NT-4/5 exhibited similar effects.The dopamine-releasing agent metamphetamine stimulated substance-P-containing neurons in 1-week-old striatal slices, whereas dopamine stimulated substance-P-like immunoreactivity in 1- and 2-week old striatal cultures. The effects of dopamine and GDNF were not additive. We conclude that substance-P-containing medium-sized spiny neurons in the striatum are under both dopaminergic and growth factor control by GDNF and NT-4/5, which are both synthesized in the striatum. This adds a previously unknown role to those that have been established for GDNF in the nigrostriatal system.
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  • 160
    ISSN: 1432-0878
    Schlagwort(e): Key words: Mineralization ; Matrix vesicles ; Dentine ; Ultrastructure ; Element analysis ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract. The purpose of this study was to elucidate the mineralization process of mantle dentine by ultrastructural and element-analytical investigation of matrix vesicles and successive stages. Upper second molars of albino rats were cryofixed and embedded in resin after freeze drying. Semithin dry sections were prepared for analyzing the calcium and phosphorus concentrations in the mineralized matrix vesicles or noduli, larger mineralized islands, and the mantle dentine. For ultrastructural studies, it was necessary to reduce section contact with hydrous fluids to a minimum in order to avoid preparation artifacts. The first mineral deposits were recognized as dot-like formations both in the interior of matrix vesicles and in association with the inner vesicle membrane. This indicated the existence of mineral nucleating sites located both at the inner membrane and at calcium-phosphate-binding macromolecules in the interior of the matrix vesicles. A significantly higher mineral content was found in mineralized matrix vesicles than in the mineralized extravesicular regions of the mineralized islands, suggesting the existence of a rapidly and densely mineralizing matrix in the matrix vesicles. A significant increase in mineral content per volume proceeding from the mineralized islands to mantle dentine suggested a further increase in the density of mineral.
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  • 161
    ISSN: 1615-6102
    Schlagwort(e): Aging ; Alzheimer's disease ; Brain ; Cell-free system ; Membranes ; Membrane trafficking ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary A cell-free transfer system was used to measure capacity of brain membranes to support membrane renewal. To study transfer in brain, radiolabeled donor microsome fractions were prepared using brain slices from rats or frozen human brain autopsy specimens. Acceptor fractions, prepared from fresh or frozen rat brain or frozen human brain autopsy specimens, were immobilized on nitrocellulose. The complete reconstituted transfer system contained ATP plus ATP-regenerating system (or NADH) as a source of energy and brain cytosol. Slices of frozen brain incorporated acetate into membrane lipids with approximately the same efficiency as fresh brains. This efficiency declined with storage at 4 °C but only slowly. Donor fractions labeled with acetate from frozen slices exhibited specific transfer (37 °C minus 4 °C) of labeled membrane lipids with efficiencies comparable to fresh. The acceptor fraction could be prepared either from fresh or frozen material. Transfer was on the average two-fold stimulated by ATP at 37 °C compared to no ATP. Transfer also was stimulated by NADH. Analysis of linear transfer rates between 0 and 30 min revealed no significant effect of delay time or of time of prolonged storage on transfer efficiency beyond an initial decline of ca. 25% observed within the first two weeks after freezing. A decline of transfer was obtained with brains as the animals aged.
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  • 162
    ISSN: 1619-7089
    Schlagwort(e): Pinhole collimator ; Single-photon emission tomography ; High resolution ; Myocardial infarction ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The purpose of this study was to evaluate the accuracy of myocardial imaging by means of high-resolution single-photon emission tomography (SPET) with a pinhole collimator in rats with experimental infarction. Myocardial infarctions were induced in male Wistar rats by ligation of the left coronary artery for 30 min, followed by reperfusion. Two days after the reperfusion, pinhole SPET was performed after the intravenous administration of 111 MBq of thallium-201 chloride, using a rotating gamma camera equipped with a pinhole insert (2.0-mm aperture) in a low-energy pinhole collimator. SPET projection data were collected at 6° increments over 360° using a 4-cm radius of rotation to reconstruct the short- and long-axis images. Projection data were acquired in 15 or 30 s, the SPET imaging being accomplished within 40 min after the injection of201T1. After SPET, the rats were sacrificed to remove the hearts for autoradiography (ARG) and nitroblue tetrazolium (NBT) staining as a visual correlative study. Quantitative correlative studies between pinhole SPET and ARG were performed with linear regression analysis for infarct size and distribution properties (relative counts on SPET images and relative density on autoradiographs) on the short-axis sections. All infarcts (4 mm in minimum diameter) in seven rats were detected by pinhole SPET. The SPET images in rats with or without myocardial infarction were consistent with the findings of ARG and NBT staining. There were significant correlations between pinhole SPET and ARG with respect to the infarct size (r=0.933,P 〈0.001;n=15) and the relative radiotracer distribution (r=0.931,P 〈0.001; n=68). This study therefore confirmed the accuracy of myocardial pinhole SPET imaging in rats with myocardial infarction. This method may partially substitute for ARG and prove useful for assessing new myocardial imaging agents in vivo in small laboratory animals.
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  • 163
    Digitale Medien
    Digitale Medien
    Springer
    European journal of applied physiology 73 (1996), S. 130-135 
    ISSN: 1439-6327
    Schlagwort(e): Experimental auto-immune encephalomyelitis ; T-Cells ; Rat ; Auto-immunity ; Exercise
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The aim of the study was to determine whether different programmes of exercise influence adoptive monophasic experimental auto-immune encephalomyelitis (adoptive EAE), a paralytic disease mediated by T-cells. Adoptive EAE was induced by the transfer of activated encephalitogenic T-lymphocytes into syngeneic recipients (Lewis rats, n = 85) and its development was followed by two independent observers. The results showed that 2 days of severe exercise (250 and 300 min) performed after the adoptive transfer of EAE slightly delayed the onset of the disease (P 〈 0.008) and the day of its maximal severity (P 〈 0.016) without affecting the overall severity of the disease. When this programme of exercise was performed before the cell transfer, it had no effect (P 〉 0.05). Two more moderate exercise programmes (5 × 120 min of running at constant speed or 5 × 60 min of running at variable speed, 5 consecutive days) performed between the adoptive transfer and the onset of the disease did not modify the development of the clinical signs of adoptive EAE (P 〉0.05). These results showed that severe exercise slightly influenced the effector phase of monophasic EAE and confirmed that physical exercise performed before the onset of experimental auto-immune diseases did not exacerbate the clinical signs.
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  • 164
    ISSN: 1439-6327
    Schlagwort(e): Short-term dietary change ; Glycogen Triacylglycerol ; Lipolysis ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects of short-term diet change from high fat (F) to high carbohydrate (C) (or vice versa) on the storage and utilization of glycogen and triacylglycerol (TG) in muscle and liver were studied in untrained rats. Rats were fed on an F or C diet for 28 days. For an additional 3 days, half of the rats in both F and C groups were fed the same diets as before (F-F and C-C) and the other half of the rats were switched to the counterpart diets (F-C and C-F). On the final day of the experiment, half of the rats in each diet group were exercised by swimming for 1.5 h and the other half were rested. Short-term diet change from F to C diets increased, but the change from C to F diets decreased, glycogen stores of soleus and plantaris muscles and liver, resulting in no difference in glycogen stores between F-C and C-C, and between F-F and C-F. The dietary change also had an affect on TG stores of red gastrocnemius muscle and liver - however, muscle TG stores were still higher in F-C than in C-C and C-F, and there were no differences in liver TG stores between F-C and C-F. Exercise decreased muscle glycogen contents markedly in F-C and C-C, whereas, it decreased muscle TG concentrations in F-F and C-F. Liver glycogen depletion was lower in F-C than in other groups. Lipolytic activities of epididymal adipose tissue at rest and postexercise were no differences between F-F and F-C, and were higher in F-C than in C-C and C-F. β-adrenergic receptor binding was determined with [125I] iodocyanopindolol, and maximal numbers of β-adrenergic receptor of plasma membrane from perirenal adipose tissue were approximately 170%–200% higher in F-C than in other groups at rest and postexercise. These results suggested that short-term C diet fed rats adapted to F diet enhanced not only glycogen stores of muscle and liver but also did not decrease lipolytic activity of adipose tissue with increased β-adrenergic receptor density, resulting in the preservation of energy reserves (glycogen and TG) of muscle at rest, and liver glycogen sparing during exercise.
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  • 165
    Digitale Medien
    Digitale Medien
    Springer
    European journal of applied physiology 72 (1996), S. 496-501 
    ISSN: 1439-6327
    Schlagwort(e): Hyperthyroidism ; Glycogen ; Skeletal muscles ; Exercise ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The aim of the present study was to examine the rate of glycogen mobilization during exercise and the rate of the postexercise glycogen replenishment in different muscle types [white (WG), and red (RG) gastrocnemius, soleus (S) and diaphragm (D)] in rats treated with triiodothyronine (T3, group T). Rats of the control group (C) were treated with saline. The animals were made to run on a treadmill set at 0° gradient and at a speed of 1200 m·h−1. The time taken to reach exhaustion in group C was 188 (SD 23) min, whereas in group T, it was only 63 (SD 12) min. The content of glycogen in all muscles of the rats from group T at rest and during exercise was significantly lower than in group C at each corresponding time. At exhaustion, the glycogen content was in WG(C) 34.79 (SD 4.65), (T) 20.10 (SD 4.10); in RG(C) 22.82 (SD 4.66), (T) 16.50 (SD 2.00); in S(C) 14.85 (SD 2.48), (T) 11.90 (SD 2.93); in D(C) 18.18 (SD 3.49), (T) 7.54 (SD 3.36) (μmol of glucosyl units·g−1). The amount of glycogen mobilized during exhausting exercise in RG, S and D was similar in both groups whereas in WG it was much higher in rats of group T than in group C. The concentration of glycogen returned to pre-exercise values in each muscle 3 h after exercise. The net amount of glycogen resynthetized during 3 h of recovery depended on the muscle type. It was in WG(C) 3.30, (T) 18.03; in RG(C) 21.34, (T) 25.88, in S(C) 34.00, (T) 17.68, and in D(C) 17.25, (T) 12.22 μmol of glucosyl units·g−1 (each number represents the difference between the means). It concluded that treatment with T3 markedly affects this exercise-induced metabolism of glycogen in each muscle type. From our study it is suggested that low muscle glycogen content may contribute to a reduction in exercise performance in hyperthyroidism.
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  • 166
    Digitale Medien
    Digitale Medien
    Springer
    International urogynecology journal 7 (1996), S. 30-36 
    ISSN: 1433-3023
    Schlagwort(e): Aging ; Incontinence ; Rat ; Smooth ; Sphincter ; Striated ; Urethra
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Muscles in the limbs change with age, but the aging process of urethral muscles is unknown. Therefore, we compared smooth and striated muscle content in the female rat urethra in young (12 month) and old (32 month) animals, using immunochemical techniques. All the striated skeletal fibers at both ages contain slow myosin. Urethral diameter does not change with age (young, 1.44±0.08 mm; old, 1.46±0.10 mm,n=5), nor does the external sphincter width (young, 0.088±0.016 mm; old, 0.080±0.017 mm,n=5). Neither smooth nor skeletal muscle volume in the urethra is changed with age (skeletal: young, 20.72±2.94%; old, 19.95±2.35%. Smooth: young, 22.26±2.98%; old, 26.75±2.35%,n=5). The external striated sphincter is separate and distinct from the pubococcygeal region of the levator ani muscle, but is closely apposed to another layer of longitudinally oriented fibers into the vaginal musculature. The morphometric analysis shows no difference in urethral architecture in aging female rats.
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  • 167
    ISSN: 1438-8359
    Schlagwort(e): Cervical sympathectomy ; Gonadotropin-releasing hormone ; Hypothalamus ; Median eminence ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract To examine the effects of cervical sympathectomy on the transport of gonadotropin-releasing hormone (GnRH) between the hypothalamic neurons and the median eminence, 16 male rats were assigned into four groups: control (C), light (L), light-sympathectomy (LS), and light-colchicine (LC). The C group was kept under a normal circadian rhythm for 2 weeks, and the L group was kept under continuous exposure to light for the same period. The LS group underwent bilateral cervical sympathectomy before being kept under continuous light conditions for 2 weeks. The LC group received colchicine into the cerebral ventricle after being kept under continuous light for 12 days; subsequently, this group was also housed for 2 days under continous light. After these procedures, blood was collected and serum luteinizing hormone (LH) levels were measured. All rats were perfused with a fixative, and GnRH neurons around the anterior commissure, as well as GnRH fibers and granules in the median eminence, were stained immunohistochemically. The L group showed a decreased number of GnRH neurons, increased concentrations of GnRH fibers and granules, and an increased LH level; however, in the LS and LC groups, these changes were not seen. The response in the LS group resembled that in the LC group. Considering the action of colchicine, which inhibits axonal transport, it is suggested that cervical sympathectomy also inhibits axonal transports of GnRH between the GnRH neurons and the median eminence during continuous exposure to light.
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  • 168
    Digitale Medien
    Digitale Medien
    Springer
    European archives of oto-rhino-laryngology and head & neck 253 (1996), S. 214-221 
    ISSN: 1434-4726
    Schlagwort(e): Formalin fixation ; Mucous cell ; Submandibular gland ; Morphology ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The features of mucous cells in 10% formalin (FA)-fixed submandibular glands differ markedly from those fixed in glutaraldehyde (GA). We therefore studied morphological changes in mucous cells during 10% FA fixation. Mucous cells were fixed in either 10% FA, neutral sodium-phosphate-buffered (Na-PBed) 10% FA, ice-cold 10% FA or an ice-cold fixative mixture of 2.0% paraformaldehyde (PA) and 0.5% GA. Two different methods were used: immersion fixation and venous perfusion fixation. The 10% FA-fixed tissues had elliptical or flattened nuclei, a clear cytoplasm and no secretory granules. Tissues fixed with the fixative mixture displayed almost round nuclei, a broad endoplasmic reticulum and abundant secretory granules in the cytoplasm. Tissues immersion-fixed with neutral Na-PBed 10% FA or perfusion-fixed with ice-cold 10% FA had almost the same light microscopic appearance as that of the mixture-fixed tissues. To elucidate the process of morphological changes during 10% FA fixation at room temperature, samples immersed in 10% FA for varying periods of time were postfixed immediately in the fixative mixture and exposed to microwave irradiation. This method produced a variety of findings, even within the same section. There was a significant difference in the findings seen in the center of the section and at the periphery. The initial changes caused by 10% FA were rupture of the secretory granules located in the perinuclear region and destruction of the perinuclear organelles such as Golgi apparatus, mitochondria and endoplasmic reticulum. Absorption of the endoplasmic reticulum progressed so that the pennuclear region became translucent. To obtain a better structure in mucous cells from the fixed submandibular gland tissues, an appropriate fixative such as GA should be used and the fixative should infiltrate into the tissue as quickly as possible.
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  • 169
    Digitale Medien
    Digitale Medien
    Springer
    European archives of oto-rhino-laryngology and head & neck 253 (1996), S. 142-146 
    ISSN: 1434-4726
    Schlagwort(e): Immunocompetent cells ; Mucosal immune system ; Larynx ; Immunohistology ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The larynx can be divided into a supraglottic, a glottic and a subglottic area, each serving different functions. In many cases of laryngitis the site of infection is located in one area, leaving other areas unaffected. It seems reasonable to speculate that the underlying cause of the heterogeneous infection pattern in the larynx is the different processing of infectious agents. Therefore, the number and distribution of granulocytes, macrophages, dendritic cells, natural killer cells and T and B lymphocytes in the normal laryngeal mucosa of young rats were studied. The results show that, with the exception of granulocytes, all subpopulations were present in different numbers. Many macrophages and dendritic cells but only a few natural killer cells and T and B lymphocytes were located in the mucosa. Dendritic cells, natural killer cells and T and B lymphocytes were rarely present in the vocal fold area, whereas in the subglottic area they were present in high numbers. Thus, differences in the composition of immunocompetent cell populations between laryngeal areas were detectable.
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  • 170
    Digitale Medien
    Digitale Medien
    Springer
    European archives of oto-rhino-laryngology and head & neck 253 (1996), S. 201-204 
    ISSN: 1434-4726
    Schlagwort(e): Endolymph potassium ; Ion-selective microelectrode ; Noise exposure ; Deafness ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Double-barrelled potassium selective microelectrodes (K-ISME) were used in situ for real-time sequential determinations of potassium concentrations (CK+) in endolymph, marginal cells and the spiral ligaments of rats exposed to moderate noise at 100 dB for 30 min (NE) and control (CTL) animals. CK+ in NE animals at these sites did not differ significantly when compared to CK+ in CTL animals. However, there was a slight decrease in CK+ in marginal cells in the noise-exposed animals.
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  • 171
    Digitale Medien
    Digitale Medien
    Springer
    Medical molecular morphology 29 (1996), S. 28-36 
    ISSN: 1860-1499
    Schlagwort(e): Swimming test ; Skeletal muscle ; Rat ; Temperature ; Light and electron microscopy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Structural changes in rat skeletal muscle induced by swimming to exhaustion were investigated by light and electron microscopy. Male Wistar rats were divided into four groups: a 28°C swimming groups, a 42°C swimming group, and non-swimming control groups at each of these temperatures. The experimental animals were tested in water for 32 min. Immediately after the swimming test, under pentobarbital intravenous anesthesia, the extensor digitorum longus muscle (EDL) and the soleus muscle (SOL) of each animal were removed from the right hindleg. Light microscopy revealed structural changes such as atrophy and focal necrosis in both muscles in animals swimming at 28 and 42°C. In some animals swimming at 42°C, an inflammatory reaction was noted around severely necrotic lesions in the EDL. A few structural changes indicative of mild atrophy were observed in the control animals. Electron microscopy revealed swelling of the sarcoplasm, swelling of the mitochondria, and disorganization or disappearance of myofilaments in various degrees in the atrophic and focal necrotic muscles of the animals swimming at 28 and 42°C. The degree of these structural changes in skeletal muscle fibers was more conspicuous in the animals swimming at 42°C than at 28°C, and more marked in the EDL than in the SOL.
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  • 172
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Electrophoresis 17 (1996), S. 198-202 
    ISSN: 0173-0835
    Schlagwort(e): Stress proteins ; Two-dimensional polyacrylamide gel electroporesis ; Rat ; Liver ; Kidney ; Perfluorocarboxylic acid ; Toxicology ; Chemistry ; Biochemistry and Biotechnology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Recent studies in this laboratory and by others suggest that two-dimensional polyacrylamide gel electrophoresis of proteins (2-DE) possesses significant utility in the detection of chemical toxicity and in providing information regarding toxic mechanism. After having identified a set of specific heat-shock and glucose-regulated proteins whose expression in rodent liver and kidney is highly conserved and constitutive, we compared the effect of in vivo exposure to perfluoro-n-octanoic acid and perfluoro-n-decanoic acid on their expression. The following stress proteins were identified, their x, y coordinate positions mapped, and abundance statistically analyzed and compared: hsp32, hsp60, hsc70, hsp70, hsp90, grp75, grp94, protein disulfide isomerase (PDI), and ER60. We report here that the stress response to perfluorocarboxylic acids is tissue-, toxicant-, and stress protein class-specific and dose-related. Furthermore, because nearly all of the proteins studied were constitutively expressed at detectable levels in both liver and kidney, the 2-DE stress protein pattern may be suitable to future toxicologic screening applications.
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    Materialart: Digitale Medien
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  • 173
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 40 (1984), S. 1004-1006 
    ISSN: 1420-9071
    Schlagwort(e): Rat ; adrenocortical responsiveness ; ACTH ; plasma ; corticosterone ; plasma ; corticotropin releasing factor (CRF)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary In the course of studying the plasma adrenocorticotropic hormone (ACTH) and corticosterone responses to synthetic corticotropin releasing factor (CRF), we noted some disparity in the responses. A higher dose (20 μg compared with 5 μg per rat i.a.) produced an equal plasma ACTH but greater plasma corticosterone response in adult male rats. Thus, we examined the possibility that CRF increases adrenocortical responsiveness to ACTH. CRF significantly (p〈0.0005) increased the plasma corticosterone response to ACTH in rats pretreated with dexamethasone. Thus, synthetic CRF increases corticosterone secretion in rats not only by stimulating ACTH secretion, but also by increasing the adrenocortical responsiveness to ACTH.
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  • 174
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 40 (1984), S. 974-975 
    ISSN: 1420-9071
    Schlagwort(e): Rat ; prostaglandins ; gastric lesion ; intragastric distension model ; stress model ; indomethacin ; somatostatin preventive effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary The inhibition of endogenous prostaglandin synthesis by indomethacin treatment blocks the somatostatin preventive effect on the gastric lesions induced in a stress model and has no preventive effect on an intragastric distension model.
    Materialart: Digitale Medien
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  • 175
    ISSN: 1432-2072
    Schlagwort(e): Opiates ; Naloxone ; Sodium preference ; Saline consumption ; Thirst ; Sex ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects of naloxone on fluid consumption by water-deprived rats trained to choose between a saline solution and water in a 15-min drinking test were examined. Rats of each sex were allocated to three groups and given access to 0.125% NaCl, 0.6% NaCl, and 1.7% NaCl, respectively, as the alternative to water. Under control conditions they drank substantially more of the hypotonic salt solutions than water, but drank slightly more water than hypertonic salt solution. Naloxone generally reduced fluid consumption, dose-dependently (0.01–10 mg/kg). In the cases of the two hypotonic solutions, the suppressant effect of naloxone was limited to saline solution. The usually low levels of water consumption were unaffected. In the case of the hypertonic solution, naloxone suppressed salt and water intakes by equivalent amounts. The effects of naloxone in the tests with the two higher salt concentrations depended upon sex. There was one example of a significant naloxone-induced reduction in saline preference (females; 0.125% NaCl v H2O). In other instances, saline preferences were not significantly modified. The results are briefly discussed in relation to current suggestions that naloxone may affect fluid consumption in ways which are taste-dependent (e.g., taste sensitivity, palatability, reward). An alternative view is also considered, that the effects of naloxone may be taste-independent, at least in the particular case of drinking in a two-choice test with saline and water.
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  • 176
    ISSN: 1432-2072
    Schlagwort(e): Conditioned reinforcement ; d-Amphetamine ; Nucleus accumbens ; Caudate nucleus ; Thalamus ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Stimulant drugs have been shown to enhance the control over behaviour exerted by stimuli previously correlated with primary reinforcers, termed conditioned reinforcers (CR). Experiment 1 examined the possible neuroanatomical specificity of the enhancement of conditioned reinforcement following intracerebral injections ofd-amphetamine. Thirsty rats were trained to associate, a light with water. In the test phase, water was no longer presented but the light (CR) was intermittently produced by responding on one of two novel levers. Rats with bilateral guide cannulae aimed at the nucleus accumbens, posterior caudate nucleus, or medio-dorsal nucleus of the thalamus received four counterbalanced microinfusions ofd-amphetamine (10, 20, 30 μg/2 μl) or vehicle (control) over 4 test days. There was a dose-dependent selective increase in responding on the lever that produced the light (CR) with intra-accumbensd-amphetamine infusions. Quantitatively similar, but much more variable effects were found with intra-caudate infusions and no effects following intra-thalamicd-amphetamine. Experiment 2 provided evidence that the enhanced control over responding by a CR with intra-accumbensd-amphetamine is behaviourally specific. Three groups of rats received a compound tone — plus —light stimulus that was positively, negatively or randomly correlated with water during training. Intra-accumbensd-amphetamine produced selective increases in responding only if the contingent stimulus had been positively correlated. The results suggest that the nucleus accumbens may play an important role ind-amphetamine's enhanced control over behaviour exerted by conditioned reinforcers.
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  • 177
    ISSN: 1432-2072
    Schlagwort(e): Citalopram ; Antidepressant ; Long-term treatment ; Hypermotility ; Dopamine receptors ; Serotonin receptors ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effect of prolonged administration of the potent and specific 5-HT uptake inhibitor citalopram on behavioural measures of dopaminergic and serotonergic activity has been studied in rats. Administration of citalopram in the diet at a daily dose of 99 μmol/kg led to supersensitivity to d-amphetamine-induced hypermotility and stereotypy and to subsensitivity to apomorphine-induced hypomotility 2 h after withdrawal. Forepaw clonus induced by 5-methoxy-N,N-dimethyltryptamine was decreased 2 h and 24 h after withdrawal and the number of head shakes induced by 1-5-HTP and citalopram were decreased 24 h after withdrawal. The d-amphetamine potentiation was still seen after 24 h, whereas the response had returned to normal 3 and 7 days after withdrawal. The content of amphetamine in three different brain regions was about 50% higher compared with controls 24 h after withdrawal of prolonged citalopram administration. At this time citalopram had been eliminated, and citalopram itself could not affect amphetamine metabolism. Other experiments indicated a linear relation between d-amphetamine brain concentration and motility level. Thus, a 50% increase in citalopram-treated rats cannot alone account for 3-fold increase in d-amphetamine-induced motility. Potentiation of d-amphetamine-induced hypermotility was also found after citalopram in a daily dietary dose of 25 μmol/kg for 13 days and after oral bolus injection (49 μmol/kg twice daily for 14 days). Acute citalopram injection had no effect in any of these models. The results suggest increased responsiveness of dopaminergic mechanisms mediating hypermotility, and decreased sensitivity of dopamine receptors mediating sedation (proposed autoreceptors). Sensitivity of 5-HT receptors was also decreased. The mechanisms by which citalopram induces d-amphetamine supersensitivity as well as subsensitivity to apomorphine and 5-HT agonists are presently unknown, since no changes in dopaminergic and serotonergic receptor binding have been found after an identical dose regimen.
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  • 178
    ISSN: 1432-2072
    Schlagwort(e): Rotational behavior ; Amphetamine ; Apomorphine ; Sensitization ; Sex differences ; Gonadal hormones ; Reverse tolerance ; 6-Hydroxydopamine ; Amphetamine psychosis ; Conditioning ; Dopamine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Factors influencing the behavioral sensitization (“reverse tolerance”) produced by intermittent amphetamine (AMPH) injections were studied by quantifying rotational behavior in rats that had a unilateral 6-hydroxydopamine lesion of the substantia nigra. The results indicate that (1) a single injection of a low dose of AMPH enhances rotational behavior induced by a second injection of AMPH for up to 12 weeks; (2) multiple, weekly injections of AMPH produce a progressive enhancement in rotational behavior, over-and-above that produced by a single injection; (3) female rats show more robust sensitization than males following single or multiple injections of AMPH; (4) this sex difference may be due to the suppression of sensitization by an androgen, because removal of testicular hormones potentiates sensitization; (5) the long-lasting sensitization of rotational behavior produced by infrequent injections of AMPH is not due to drug-environment conditioning effects, but perhaps to a persistent AMPH-induced change(s) in brain catecholamine systems; and (6) a simple change in DA receptors is probably no involved, because the sensitization produced by infrequent injections of AMPH does not influence the rotation produced by a subsequent injection of apomorphine. The results illustrate an intriguing example of neuroplasticity that may have clinical relevance.
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  • 179
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 84 (1984), S. 541-543 
    ISSN: 1432-2072
    Schlagwort(e): Morphine ; Cholecystokinin ; Proglumide ; Locomotion ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Proglumide (0.02 mg/kg), a cholecystokinin antagonist, was administered to rats either together with or without morphine (0, 5, 15, or 45 mg/kg). Whereas proglumide in the absence of morphine showed a trend towards enhanced behavioral activation, it potentiated the hy[okinesia induced by morphine. These results are consistent with the hypothesis that endogenous cholecystokinin tonically antagonizes opiate modulation of motility, irrespective of whether such modulation is produced by opiates and endogenous or exogenous origin.
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  • 180
    ISSN: 1432-2072
    Schlagwort(e): Naloxone ; Methamphetamine ; Apomorphine ; Haloperidol ; Stereotypy ; Catalepsy ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Pretreatment with the opiate antagonist naloxone, at 1.25–5 mg/kg, increased the intensity of methamphetamine stereotypy, had no effect (over a range of 0.3125–5 mg/kg) on apomorphine stereotypy, and antagonized haloperidol catalepsy in rats at 1.25–5 mg/kg. It is suggested that naloxone, by blocking the opiate receptors located on the nigro-striatal and mesolimbic dopamine (DA) nerve terminals, releases the DA systems from endogenous inhibition, presumably caused by endogenous opiate systems, and thereby potentiates methamphetamine stereotypy and antagonizes haloperidol catalepsy. However, the possibility that naloxone might have affected methamphetamine stereotypy and haloperidol catalepsy by modulating the activity of the central noradrenergic and GABAergic systems, which are reported to influence dopaminergically mediated behaviours, also needs to be considered.
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  • 181
    ISSN: 1432-2072
    Schlagwort(e): Punishment-induced suppression ; Diazepam ; Serotonin ; Dorsal raphé ; Substantia nigra ; 5,7-Dihydroxytryptamine ; Ro 15-1788 ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effects of manipulating central serotonergic transmission were assessed on the anti-punishment effects of diazepam (2 mg/kg IP) in rats. In a paradigm involving the inhibition of pressing for food induced by the delivery of a signal previously associated with electric foot-shocks, lesioning serotonergic neurons of the dorsal raphé with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 1 μg in 0.4 μl) neither affected behavioral inhibition in control rats nor modified the ability of diazepam to release responding. Furthermore, suppression of pressing for food induced by a fixed ratio 7 schedule of shock presentation was reduced by bilateral infusion of 5,7-DHT (2 μg in 0.5 μl) into the substantia nigra, but the ability of diazepam to increase punished responding was preserved. Finally, blockade of benzodiazepine-induced decrease in serotonin release by application of the benzodiazepine receptor antagonist Ro 15-1788 (10−5–10−4 M in 0.2 μl) into the dorsal raphé did not alter the releasing effect of diazepam on suppression of pressing for food caused by a signal of punishment. At these concentrations. Ro 15-1788 was devoid of any effect on behavioral inhibition in control rats. Taken together, these results indicate that the anti-punishment activity of benzodiazepines can be dissociated from the reduction in tryptaminergic transmission produced by these drugs.
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  • 182
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 83 (1984), S. 194-199 
    ISSN: 1432-2072
    Schlagwort(e): Chronic amphetamine ; Latent inhibition ; Conditioned suppression ; Schizophrenia ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The animal amphetamine model of schizophrenia has been based primarily on stereotyped behavior. The present study sought to demonstrate an amphetamine-induced deficit in attentional processes. To this end, the effects of acute and chronic (14 days) 1.5 mg/kg dl-amphetamine administration on the ability of rats to ignore irrelevant stimuli were examined using the paradigm of latent inhibition (LI) in a conditioned emotional response (CER) procedure. The procedure consisted of three stages: pre-exposure, in which the to-be-conditoned stimulus, tone, was presented without being followed by reinforcement; acquisition, in which the pre-exposed tone was paired with shock; and test, in which LI was indexed by animals' suppression of licking during tone presentation. Experiment 1 showed that chronic but not acute treatment abolished LI. Experiment 2 showed that animals receiving chronic amphetamine pretreatment but pre-exposed and conditioned without the drug, exhibited normal LI. In Experiment 3, animals which received chronic amphetamine pretreatment and were pre-exposed under the drug but conditioned without it, also showed normal LI. The implications of these results for the animal amphetamine model of schizophrenia are discussed.
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  • 183
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 83 (1984), S. 257-261 
    ISSN: 1432-2072
    Schlagwort(e): Drug discrimination ; Reinforcement variables ; Fentanyl ; Morphine ; Sufentanil ; Naloxone ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rats were trained to discriminate between fentanyl (0.04 mg/kg) and saline in a two-lever procedure. Using a FR 10 schedule of food reinforcement, drug-induced differences between the number of reinforcers obtained under fentanyl and saline conditions were observed. The effect of eliminating these differences on the outcome of generalization tests was investigated by different manipulations. In one group (N=10), the FR 10 schedule used during saline sessions was changed to FR 6 during drug sessions. In a second group (N=12), saline sessions ended after the number of reinforcers obtained was equal to the number obtained during the preceding drug session. A control group (N=10) was trained using a FR 10 schedule under both conditions. Elimination of differences in reinforcement frequency 1) accelerated the acquisition of the discrimination, 2) diminished response bias, 3) flattened the slope and reduced the ED50 value of generalization gradients of fentanyl, morphine and sufentanil and 4) increased the ED50 value of naloxone in antagonizing 0.04 mg/kg fentanyl. It is concluded that the unconditioned effects of 0.04 mg/kg fentanyl on response rate in a FR 10 procedure lead to differences between saline and drug sessions which contribute to the apparent discriminative stimulus properties of fentanyl.
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  • 184
    ISSN: 1432-2072
    Schlagwort(e): β-Carbolines ; Drug discrimination ; Benzodiazepine ; Diazepam ; Chlordiazepoxide ; Pentylenetetrazol ; Anxiety ; FG 7142 ; ZK 93423 ; ZK 91 296 ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The discriminative stimulus properties of three β-carboline derivatives were studied in three groups of rats trained, respectively, to discriminate diazepam (2.5 mg/kg IP), chlordiazepoxide (CDP, 5 mg/kg IP) or pentylenetetrazol (PTZ, 15 mg/kg IP) from saline in standard procedures employing two-lever operant chambers. Two β-carbolines, ZK 91296 and ZK 93423, substituted for the benzodiazepines in both CDP- and diazepam-trained rats. The neutral benzodiazepine antagonist Ro 15-1788 blocked the diazepam discriminative stimulus and the ability of ZK 91296 to substitute for diazepam. A third β-carboline, FG 7142, was not identified as benzodiazepine-like in generalization tests in either diazepam- or CDP-trained rats, but when administered together with CDP antagonized the benzodiazepine discriminative stimulus. In rats trained to discriminate PTZ from saline (a discrimination which is thought to depend on the anxiogenic properties of PTZ) the PTZ cue was antagonized by diazepam and ZK 93423, and partially antagonized by ZK 91296. The PTZ cue generalized to FG 7142 and this generalization was partially antagonized by Ro 15-1788. These results suggest that the three β-carbolines provide more than one kind of discriminative stimulus, consistent with the classification of ZK 93423 as an agonist at central benzodiazepine receptors, with ZK 91 296 as a partial agonist, and with FG 7142 as an inverse agonist. Pharmacologically, ZK 93 423 and ZK 91 296 may exhibit anxiolytic qualities, whereas FG 7142 produces anxiogenic effects.
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  • 185
    ISSN: 1432-2072
    Schlagwort(e): Benzodiazepine receptors ; β-Carboline-3-carboxylates ; Anxiety ; Epilepsy ; Ataxia ; Rat ; Mouse
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract ZK 91296 (ethyl 5-benzyloxy-4-methoxymethyl-β-carboline-3-carboxylate) is a potent and selective ligand for benzodiazepine (BZ) receptors. Biochemical investigations indicate that ZK 91296 may be a partial agonist at BZ receptors. Such partial agonism may explain to some extent why ZK 91296 needs higher BZ receptor occupancy than diazepam for the same effect against chemical convulsants and for behavioural effects. The lack of sedatiye effects, and the very potent inhibition of reflex epilepsy, spontaneous epilepsy and DMCM-induced seizures suggest, furthermore, that ZK 91296 may possess pharmacological selectivity for a particular type of BZ receptor interaction, perhaps including topographic as well as receptor subtype differentiation.
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  • 186
    ISSN: 1432-2072
    Schlagwort(e): ZK 93426 ; Ro 15-1788 ; CGS 8216 ; Benzodiazepine receptor agonists ; Benzodiazepine receptor antagonist ; Benzodiazepine receptor inverse agonist ; Rat ; Mouse
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We describe here biochemical and pharmacological effects of the β-carboline ZK 93426, a new and potent benzodiazepine (BZ) receptor antagonist. ZK 93426 was compared with Ro 15-1788 and CGS 8216, two compounds previously described as BZ receptor antagonists. Certain effects of ZK 93426, Ro 15-1788 and CGS 8216 were quite similar (e.g., 3H-FNM displacement, “GABA ratio”, “photo-shift”). In most pharmacological tests ZK 93426 and Ro 15-1788 lacked overt effects; Ro 15-1788 was a weak agonist in some paradigms, while ZK 93426 exhibited a potent proconflict effect but also a weak anticonvulsant effect. This interesting finding with ZK 93426 suggests that BZ receptor ligands may possess differential efficacy at BZ receptor subtypes. In contrast, CGS 8216 exhibited potent proconvulsant effects in several paradigms in addition to proconflict and pentylenetetrazol generalizing effects. ZK 93426, Ro 15-1788 and CGS 8216 were almost equally potent as antagonists of the effects of BZ receptor agonists, such as diazepam and lorazepam. However, ZK 93426 was the most potent inhibitor of the convulsions produced by the BZ receptor inverse agonist DMCM.
    Materialart: Digitale Medien
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  • 187
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 83 (1984), S. 277-280 
    ISSN: 1432-2072
    Schlagwort(e): Chlordiazepoxide ; Metrazol ; Audiogenic seizures ; Resistance to extinction ; Resistance to punishment ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Three experiments were carried out to test the long-term behavioral effects of 12 days administration of CDP (5 mg/kg/day) in rats. In the first two experiments, 4 weeks after the end of drug administration (CDP or placebo), and after 2 weeks of training to run a straight alley for food reward, animals were tested in extinction, i.e., following omission of reward (Expt. 1) or with punishment, i.e., 0.3 mA electric shock in addition to the food reward (Expt. 2). Drug-treated animals showed significantly increased resistance to extinction and to punishment compared with controls. In the third experiment, 10 weeks after drug administration, animals were exposed to 60 s of intense noise to induce audiogenic seizures. The convulsant metrazol was injected 5 min prior to successive sessions (10 min apart) with doses starting at 10 mg/kg and increased by 10 mg/kg each session up to 40 mg/kg. Drug-treated animals were significantly less susceptible to seizures than their placebo controls. These results suggest that chronic benzodiazepine treatment causes long-term neurochemical changes which are responsible for the observed behavioral effects.
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  • 188
    ISSN: 1432-2072
    Schlagwort(e): (+)-Amphetamine ; Self-administration ; Dopaminergic neurons ; Acquisition ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effect of 6-OHDA lesions of the dopaminergic mesocorticolimbic cell bodies on intravenous (+)-amphetamine self-administration in the rat was assessed. An acquisition paradigm was used in which the rat had to discriminate between an active and an inactive lever. Each press on the active lever delivered 7.5 μg/kg (+)-amphetamine. The lesioned animals acquired this discrimination faster and hence self-administered a larger amount of drug. Thus dysfunction of dopaminergic neurons can induce an enhanced vulnerability to drugs which may be abused by humans.
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  • 189
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 83 (1984), S. 288-292 
    ISSN: 1432-2072
    Schlagwort(e): Intracranial self-stimulation ; Enkephalins ; Morphine ; Naloxone ; Prefrontal cortex ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The possible involvement of opioid peptides as part of the neurochemical substrates of self-stimulation (SS) in the medial prefrontal cortex (MPC) of the rat was investigated in two different groups of rats bilaterally implanted with monopolar electrodes in the MPC. In the first group, morphine (5, 10 and 20 μg) and an enkephalin analogue (BW 180) (5, 10, 20 and 40 μg) and an enkephalin analogue (BW 180) (5, 10, 20 and 40 μg) were injected through cannulae implanted into the lateral ventricles (IV). In the second group, naloxone (0.04, 0.4, and 1.6 μg) and morphine (5, 10 and 20 μg) were injected through cannulae implanted into the MPC, 1.5 mm above the tip of the stimulating electrodes. In the first group, spontaneous motor activity (SMA) was measured as a control for non-specific effects (sedation or motor dysfunction). In the second group SS, contralateral to the microinjected side, served as control. SS and SMA were measured 1 and 2 h postinjection. One hour after IV injection of morphine SS was not affected, although SMA was decreased. Two hours postinjection, on the contrary, SS was increased while SMA remained decreased. Similar effects were found with IV microinjections of BW 180. Naloxone, intraperitoneally injected, reversed all these effects. Naloxone or morphine injected intracerebrally (MPC) produced no changes in SS either in the injected or in the contralateral side, which served as control. The present results suggest that the effects found with IV injections of opioids on SS of the MPC are indirect (through activation of other brain areas) and not mediated by a direct action on the neurochemical substrates underlying this behaviour in the MPC.
    Materialart: Digitale Medien
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  • 190
    ISSN: 1432-2072
    Schlagwort(e): Prolonged estradiol treatment ; Behaviour ; Rat ; Muscimol ; Apomorphine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Two months after prolonged administration of estradiol (ES) in female rats the behavioural responsiveness to muscimol, a GABA receptor stimulating agent, and to apomorphine, a dopamine receptor agonist, was significantly altered. In particular, the decrease in locomotor activity induced by a challenge dose of muscimol (0.5–1 mg/kg) was significantly attenuated in ES-pretreated animals. Conversely, the intensity of stereotyped behaviour elicited by a challenge dose of apomorphine (1 mg/kg) was significantly increased in ES-pretreated rats. The behavioural alterations in the response to muscimol and apomorphine presumably result from the production of central GABA receptor subsensitivity and dopamine receptor supersensitivity respectively, induced by the prolonged ES administration.
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  • 191
    ISSN: 1432-2072
    Schlagwort(e): Noradrenaline ; Serotonin ; Dopamine ; Beta receptors ; Antidepressants ; Thiopentone ; Anaesthesia ; Rat ; Iprindole ; Mianserin ; Zimelidine ; Sleeping time
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A behavioural model sensitive to manipulation of brain noradrenaline systems and with characteristics of beta-receptor mediation has been developed using the duration of thiopentone anaesthesia in the rat. Acute and chronic administration of various antidepressant agents was examined. In the acute phase, (30 min prior to thiopentone) the noradrenaline uptake-inhibiting tricyclic drugs and viloxazine increased anaesthesia duration in a dose-dependent fashion. The atypical antidepressants trazodone, iprindole, and mianserin did this only weakly, while the dopaminergic and serotonergic uptake-inhibiting antidepressants (respectively bupropion, nomifensine, and zimelidine, fluoxetine) markedly shortened anaesthesia duration. Chronic administration (for 15 days) prolonged anaesthesia duration measured 2 or 5 days after the last drug injection for all tricyclic agents, for the atypical antidepressants mianserin, iprindole, fluoxetine, and zimelidine, and for viloxazine.
    Materialart: Digitale Medien
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  • 192
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 82 (1984), S. 327-329 
    ISSN: 1432-2072
    Schlagwort(e): Reserpine ; Dextroamphetamine ; Stereotypy ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The augmentation of the rat stereotypy response with repeated amphetamine doses, put forward as a model of human amphetamine psychosis, was examined during concurrent reserpinization. The effects of reserpinization, amphetamine treatment, and amphetamine dose on four dependent variables representing the time course of stereotypy ratings after a post-treatment amphtamine dose, were tested by three-way MANOVA. An earlier onset of stereotypy, as occurred in nonreserpinized rats, was not detected in reserpinized rats, but an earlier offset of stereotypy with repeated amphetamine occurred in these rats when high amphetamine doses were used.
    Materialart: Digitale Medien
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  • 193
    ISSN: 1432-2072
    Schlagwort(e): Supersensitivity ; 5-HT1 receptors ; Methysergide ; Ketanserin ; Pirenperone ; 5-HT agonist rotational behaviour ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The rotational behaviour induced by 5-HT agonists has been investigated in rats with lesions of the dorsal raphe' nucleus (DRN). We have previously reported that 5-methyoxy-N,N-dimethyl-tryptamine (5-MeODMT) caused dose-related contralateral rotation in rats with 5,7-dihydroxytryptamine (5,7-DHT) lesions of the DRN. Similar findings are now presented for the 5-HT1 agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methoxy-3 (1,2,3,6-tetrahydropyridin-4-yl) (1H indole) (RU24969). In this model, in agreement with the behavioural studies, both agonists were shown to have a greater affinity for the 5-HT1 binding site when compared with the 5-HT2 binding site. Antagonist studies using selective 5-HT2 antagonists (ketanserin and pirenperone) at non-sedative doses failed to inhibit this behaviour. In contrast, the classical 5-HT antagonist methysergide caused significant inhibition of the rotational behaviour. These results suggest that 5-HT agonist-induced rotation in the rat is mediated via 5-HT1 receptors, probably located in the substantia nigra.
    Materialart: Digitale Medien
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  • 194
    ISSN: 1432-2072
    Schlagwort(e): Catecholamines ; Cerebroventricular perfusion ; Carbamazepine ; Imipramine ; Desmethylimipramine ; Tranylcypromine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Concentrations of endogenous norepinephrine, dopamine and epinephrine in cerebroventricular perfusates were used to evaluate the effects of drugs on the availability of extracellular catecholamines in the intact rat brain. Administration of the antidepressant drugs imipramine, desmethylimipramine or tranylcypromine resulted in marked increases of both norepinephrine and dopamine concentrations while epinephrine levels were not affected. Treatment with a similar dose of carbamazepine — an anticonvulsant drug with antidepressant activity — resulted in a significant increase in dopamine concentrations without apparent effect on either norepinephrine or epinephrine. It is suggested that at the applied dose, carbamazepine may act to modify the uptake, release or metabolism of dopamine in brain areas adjacent to the cerebroventricular space without affecting the other catecholamines.
    Materialart: Digitale Medien
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  • 195
    ISSN: 1432-2072
    Schlagwort(e): Amphetamine ; Locomotor activity ; Stereotypy ; Anorexia ; Behavioural competition ; Neostriatum ; Dopamine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The effect of 6-OHDA-induced lesions of neostriatum on locomotor activity, stereotypy and anorexia induced by amphetamine (0.5 mg/kg, 1.5 mg/kg and 5.0 mg/kg IP) was examined. Lesioned rats demonstrated attenuated stereotypy and anorexia but enhanced locomotor activity to amphetamine. Biochemical analysis of dopamine and noradrenaline in specific forebrain areas demonstrated significant dopamine depletion in neostriatum. Dopamine levels in mesolimbic, frontal cortex and hypothalamic areas, and noradrenaline in frontal cortex and hypothalamic areas, were not significantly reduced. The data were interpreted in terms of a response incompatibility hypothesis. It is proposed that stereotyped responses mediated by nigrostriatal dopamine neurones are incompatible with eating. In addition, it is suggested that a second form of competition, at the neuro-anatomical level, occurs between mesolimbic and nigrostriatal systems for motor output pathways and the ultimate expression of behaviour. The role of noradrenaline in amphetamine anorexia is also discussed.
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  • 196
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 83 (1984), S. 367-372 
    ISSN: 1432-2072
    Schlagwort(e): GABA ; Mouse-killing ; Aggressive behaviour ; GVG ; DPA ; THIP ; Picrotoxin ; Bicuculline ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract When GABA-potentiating compounds were administered IP to rats with prior experience of mouse-killing behaviour, a reduction of killing was observed with gammavinyl GABA (200 and 400 mg/kg) and nipecotic acid amide (400 mg/kg), while no significant effect was noted following injection of dipropylacetate or THIP. The inhibitory effects of gamma-vinyl GABA and nipecotic acid amide were not reversed by subsequent injection of picrotoxin and were associated with sedation as observed in open field and actograph tests. When GABA-potentiating compounds were administered to food-deprived rats exposed for the first time to a mouse (initial elicitation), administration of gamma-vinyl GABA, dipropylacetate, nipecotic acid amide or THIP increased the incidence of mouse-killing behaviour. Conversely, the incidence of mouse-killing under the same conditions was reduced following injections of picrotoxin. These results do not support the hypothesis that the general activation of GABAergic mechanisms inhibits mouse-killing behaviour in rats. On the contrary, data obtained in naive animals suggest that potentiation of these mechanisms actually facilitates the initial elicitation of this behaviour.
    Materialart: Digitale Medien
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  • 197
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 84 (1984), S. 420-422 
    ISSN: 1432-2072
    Schlagwort(e): CGS-8216 ; Benzodiazepine ; Plasma ; Pharmacokinetics ; Rat ; Brain
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract A rapid and sensitive method is described for the determination of CGS-8216 (a pyrazoloquinoline that displaces benzodiazepines from their binding sites in the brain but which reverses some of the behavioural actions of the benzodiazepines) in plasma using high-performance liquid chromatography with ultraviolet detection. CGS-9896 serves as the internal standard. The method is applied to a pharmacokinetic study of CGS-8216 in the rat. CGS-8216 was not detectable in plasma 24 h after a single IP administration of a 10 mg/kg dose. Animals treated with five once-daily injections of CGS-8216 had plasma concentrations 30 min after the final injection that were approximately four-times those observed 30 min after a single treatment. This suggests that caution must be used in the interpretation of results from experiments using multiple administrations of CGS-8216. The compound could not be detected in brain tissue at any of the time points studied.
    Materialart: Digitale Medien
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  • 198
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 84 (1984), S. 431-435 
    ISSN: 1432-2072
    Schlagwort(e): Stress ; Amphetamine ; Locomotor activity ; Dopamine ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Adult male rats submitted to mild, 20 min electric foot shock sessions for 10 days displayed an enhanced locomotor response to 0.75 mg/kg (+)amphetamine 24 h after the last shock session, when compared to non-stressed controls. This effect was still present in rats specifically deprived of their forebrain noradrenergic innervation, suggesting the involvement of a dopaminergic mechanism. Cortical and limbic dopamine turnover which increased immediately after acute and repeated foot shocks returned to normal 24 h later, at the time of the pharmacological testing. This fact indicates that a permanent modification of the basal DA activity is not responsible for the above effect apomorphine was enhanced in experimental animals, while hypoactivity resulting from the injection of 0.05 mg/kg apomorphine was similar in control and shocked rats. This latter result suggests the existence of an increased postsynaptic DA sensitivity as a result of repeated stress.
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  • 199
    Digitale Medien
    Digitale Medien
    Springer
    Psychopharmacology 84 (1984), S. 441-445 
    ISSN: 1432-2072
    Schlagwort(e): Conditioned avoidance ; Dopamine autoreceptors ; 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP) ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The administration of (-)3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP) was found to partially, but significantly, suppress the acquisition (4–8 mg/kg IP) and performance (8–16 mg/kg IP) of a conditioned avoidance response (CAR) in male Sprague-Dawley rats. All statistically significant effects were observed within 2 h of injection. Furthermore, using a situation in which the CAR was dependent on a visual successive discrimination, it was shown that discriminative performance was unaffected, and that (-)3-PPP (12.5–25 mg/kg IP) but not (+)3-PPP, suppressed the CAR. When (-)3-PPP (6.25 mg/kg IP) was combined with haloperidol (0.1–0.4 mg/kg IP), additive effects on the CAR performance were observed. Considering these effects, and the doses of (-)3-PPP required to suppress the CAR performance, it is concluded that the effects obtained in the present experiments are primarily due to a blockade of postsynaptic DA receptors.
    Materialart: Digitale Medien
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  • 200
    ISSN: 1432-2072
    Schlagwort(e): Haloperidol ; Sulpiride ; Striatum ; Supersensitivity ; Dopamine receptors ; Rat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Administration of haloperidol (1.4–1.6 mg/kg/day) for up to 12 months or sulpiride (102–109 mg/kg/day) for between 6 and 12 months increased the frequency of purposeless chewing jaw movements in rats. N,n-propylnorapomorphine (NPA) (0.25–2.0 mg/kg SC) did not induce hypoactivity in haloperidol-treated rats at any time; sulpiride treatment for 9 and 12 months caused a reduction in the ability of NPA to induce hypoactivity. Haloperidol, but not sulpiride, treatment enduringly inhibited low dose apomorphine effects (0.125 mg/kg SC). After 12 months, sterotypy induced by high doses of apomorphine (0.5–1.0 mg/kg) was exaggerated in haloperidol-, but not sulpiride-treated rats. Bmax for specific striatal 3H-spiperone binding was increased by haloperidol, but not sulpiride, treatment throughout the study. Bmax for 3H-NPA binding was elevated only after 12 months of both haloperidol and sulpiride treatment. Bmax for 3H-piflutixol binding was not alfered by chronic haloperidol or sulpiride treatment. Striatal dopamine-stimulated adenylate cyclase activity was inhibited for the 1st month of haloperidol treatment, thereafter returning to control levels; dopamine stimulation was increased after 12 months of sulpiride treatment. Striatal acetylcholine content was increased after 3 and 12 months of treatment with haloperidol, but was not affected by sulpiride. Chronic administration of sulpiride does not induce identical changes in striatal dopamine function to those caused by haloperidol.
    Materialart: Digitale Medien
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