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  • 101
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 76 (1989), S. 656-661 
    ISSN: 1432-1106
    Keywords: Central chemoreceptor ; Carbon dioxide ; Nucleus tractus solitarius ; Nucleus ambiguus ; Cardiopulmonary control ; Brain slice ; Intracellular recording ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To identify central sites of potential CO2/H+-chemoreceptive neurons, and the mechanism responsible for neuronal chemosensitivity, intracellular recordings were made in rat tissue slices in two cardiopulmonary-related regions (i.e., nucleus tractus solitarii, NTS; nucleus ambiguus, AMBc) during exposure to high CO2. When the NTS was explored slices were bisected and the ventral half discarded. Utilizing such “dorsal” medullary slices removed any impinging synaptic input from putative chemoreceptors in the ventrolateral medulla. In the NTS, CO2-induced changes in firing rate were associated with membrane depolarizations ranging from 2–25 mV (n = 15). In some cases increased e.p.s.p. activity was observed during CO2 exposure. The CO2-induced depolarization occurred concomitantly with an increased input resistance ranging from 19–23 MΩ (n = 5). The lower membrane conductance during hypercapnia suggests that CO2-induced depolarization is due to a decreased outward potassium conductance. Unlike neurons in the NTS, AMBc neurons were not spontaneously active and were rarely depolarized by hypercapnia. Eleven of 12 cells tested were either hyperpolarized by or insensitive to CO2. Only 1 neuron in the AMBc was depolarized and it also showed an increased input resistance during CO2 exposure. Our findings suggest that CO2/H+-related stimuli decrease potassium conductance which depolarizes the cell and increases firing rate. Although our in vitro studies cannot guarantee the specific function of these cells, we believe they may be involved with brain pH homeostasis and cardiopulmonary regulation.
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  • 102
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 77 (1989), S. 283-294 
    ISSN: 1432-1106
    Keywords: Intracellular recordings ; Membrane potential ; Input impedance ; Hippocampal pyramidal cells ; Theta rhythm ; Urethane ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intracellular recordings were made from hippocampal pyramidal cells identified by their depths and their responses to commissural stimulation. Recordings were made during spontaneous bouts of hippocampal theta rhythm in urethane anesthetized rats. Membrane potentials (V m) of pyramidal cells varied with the phase of the theta rhythm, that is, there was an “intracellular theta rhythm”. The changes in V m averaged about 2 mV peak to peak. Averaged intracellular theta waves showed that CA1 pyramids were most depolarized at the time of the positive peak of the extracellular theta rhythm recorded in (and superficial to) the CA1 pyramidal cell layer (CA1 theta). Peak depolarizations for CA3/4 pyramids were more broadly distributed, but occurred mainly in the interval just before the positive peak to just before the negative peak of the CA1 theta. Input impedance minima that were measurable at frequencies as high as 100 Hz occurred at about the same phases of the extracellular theta rhythm as the peak depolarizations (positive-going zero crossing to negative-going zero crossing of the CA1 theta). Such impedance changes imply conductance changes on the soma. The magnitude and localization of the conductance changes suggests that somatic IPSPs make major contributions to the intracellular theta rhythm. The phase relation between the intracellular and extracellular theta rhythms could be reversed by long duration current pulses that depolarized the cells slightly. This implies that either the intracellular theta-related IPSPs are depolarizing potential changes, or that they occur simultaneously with EPSPs. The phase of the intracellular theta rhythm was generally unaffected by long duration hyperpolarizing current pulses. Chloride leakage that reversed the evoked IPSPs usually had no effect on the phase of the intracellular theta rhythm, although in one case it appeared to cause its amplitude to increase.
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  • 103
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 77 (1989), S. 234-244 
    ISSN: 1432-1106
    Keywords: Development ; Visual cortex ; Slicecultures ; Pyramidal cells ; GABA immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Slice cultures from the visual cortex of young rats were prepared using the roller culture technique (Gähwiler 1984). After 10 days in vitro the cortical cultures flattened to 1–3 cell layers, surviving for up to 12 weeks. The cultures were organotypically organized, the typical layered structure of the cortex was preserved. The neuronal composition of slice cultures was studied using intracellular staining, Golgi impregnation and GABA immunohistochemistry. Both pyramidal cells and several types of nonpyramidal cells were identified in the slice cultures. Electrophysiological recordings showed that the electrical properties of cells in culture were similar to those measured in acute slice preparations; for some cells, however, the spontaneous activity was higher. The maintained activity was strongly increased by application of the GABA antagonist bicuculline and decreased by GABA, suggesting that GABAergic inhibition is present in these preparations. We could observe the postnatal maturation of some characteristic morphological features in culture. For example, pyramidal cells in 6 day-old rats in situ have very short basal dendrites with growth-cones, and the dendrites are free of spines. After 2–3 weeks in culture growth-cones were no longer observed. Instead, the cells had developed a large basal dendritic field and the dendrites were covered with spines. Slice cultures therefore may provide a useful tool for physiological, anatomical, pharmacological and developmental studies of cortical neurons in an organotypical environment.
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  • 104
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 77 (1989), S. 295-301 
    ISSN: 1432-1106
    Keywords: Preoptic area ; Intrinsic neuron ; GABA ; Local neuron ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neurons intrinsic to the preoptic area might participate in the control of neuroendocrine or behavioral events. To determine their existence and features, we deafferented the preoptic area of female rats, using completely circumscribing cuts with a Halasz knife. Despite obvious signs of degeneration of synapses originating from nerve cell bodies outside the preoptic island, some synapses survived complete deafferentation. We saw synaptic contacts not only on the neuronal cell body, but also on the dendritic shaft and spine. There were no peculiar morphological features, as might suggest unique physiologic functions of these intrinsic synapses. The prominence of intrinsic synapses in the preoptic area suggests that, in addition to hormone effects on preoptic neurons, and long ascending afferents, intrinsic synapses might play significant roles in neuroendocrine controls.
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  • 105
    ISSN: 1432-1106
    Keywords: Met- and leu-enkephalin ; Morphine ; Cortex ; Intracellular recordings ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The action of enkephalin-analogues (D-ala2-D-leu5-enkephalin and D-ala2-D-metenkephalin) and morphine, iontophoretically applied, was tested on rat cortical neurons intracellularly recorded “in vivo”. Inhibition of cellular excitability of 60% of the tested cells followed the iontophoretic administration of opioid peptides. 50% of the inhibited cells were also hyperpolarized. The amplitude of membrane hyperpolarization was related to the value of the membrane potential. In 13 out of the 30 inhibited cells the change in membrane input resistance was measured; the input resistance was decreased by 30%. In 8 cells, hyperpolarized by the opioid peptides, the depolarizing postsynaptic potentials, evoked by cortical stimulation, were also reduced in amplitude. Naloxone, iontophoretically applied, reversed and/or prevented the peptide responses. On the same neurons, morphine induced a bursting pattern of spiking activity and increased the membrane input resistance: this action was naloxone-insensitive. The reported results suggest that opioid peptides and morphine activate, respectively, naloxone-sensitive and naloxone-insensitive mechanisms on the same cortical neurons, leading to different and, in some respect, opposite effects on the neuronal activity.
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  • 106
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 77 (1989), S. 374-380 
    ISSN: 1432-1106
    Keywords: GABAA and GABAB receptors ; Rhythmic activity ; G-protein ; Pertussis toxin ; Septo-hippocampal pathway ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The possible involvement of GABA in the control of the rhythmical bursting activity (RBA) of septo-hippocampal neurons (SHNs) has been studied in the rat in vivo. The discharge frequency of SHNs was modified by the iontophoretic application of a GABA agonist and antagonist as well as by the application of the GABA uptake blocker, nipecotic acid. The GABAB agonist baclofen inhibited the SHNs' activity, this effect being antagonized by the GABAB antagonist phaclofen. However, these different pharmacological manipulations did not modify the RBA frequency. Pretreatment of the rats with pertussis toxin, a substance which is known to block the events mediated by G-proteins (Gi or Go), decreased the RBA frequency. Neither agonists nor antagonists of GABAA or GABAB types had significant effects on the rhythmical bursting activity of SHNs. The effect of pertussis toxin suggests that other neurotransmitters or intrinsic mechanisms involving a G-protein influence this rhythm.
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  • 107
    ISSN: 1432-1106
    Keywords: Caudate-putamen ; Neural plasticity ; Nigrostriatal projection ; Sensory deprivation ; Vibrissae ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of unilateral removal of vibrissae on the crossed and uncrossed nigrostriatal projections was examined with the horseradish peroxidase tract tracing technique. Hemivibrissotomy mainly affected the projections arising from the rostral part of the substantia nigra. One to three days after clipping the vibrissae, rats were found to have more labeled neurons in the crossed projection to the caudate-putamen (CPU) on the same side as vibrissae removal than in the crossed projection to the CPU opposite to vibrissae removal. A reversed asymmetry was seen in rats examined 4–20 days after vibrissae removal. These animals had more labeled cells in the crossed and uncrossed projections terminating in the CPU opposite to the shaved side, i.e. in the hemisphere deprived of vibrissal sensory input. This time-course of neural alterations is similar to that of the recovery from behavioral asymmetries seen after hemivibrissotomy. Similar time-dependent alterations in the nigrostriatal projection had been found after unilateral injection of 6-OHDA into the substantia nigra.
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  • 108
    ISSN: 1432-1106
    Keywords: Parvalbumin ; GABA ; Nonpyramidal cell ; Monoclonal antibody ; Lectin ; Cerebral cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Monoclonal antibody VC1.1 is shown to stain selectively a subpopulation of GABAergic neurons in the rat cerebral cortex. Almost all VC1.1 immunoreactive cells were also GABA-like immunoreactive (GABA-LI) and parvalbumin (PV) immunoreactive, whereas they were about 30% and 65% of GABA-LI and PV-positive cells in the parietal cortex and about 13% and 32% in the occipital cortex, respectively. Although a few VC1.1 positive cells showed somatostatinlike and/or cholecystokinin-like immunoreactivities, they were exceptional (less than 1% of VC1.1 positive cells). Furthermore about 90% of VC1.1 positive cells were also stained with a lectin, Vicia villosa agglutinin, with a specific affinity for terminal N-acetylgalactosamine.
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  • 109
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    Springer
    Experimental brain research 78 (1989), S. 214-218 
    ISSN: 1432-1106
    Keywords: Nigral grafts ; Adrenal grafts ; Rotation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Separate groups of rats with unilateral 6-OHDA lesions of the nigrostriatal pathway received intrastriatal foetal (E14) substantia nigra suspension grafts, intrastriatal postnatal (P22–25) adrenal medulla suspension grafts using either collagenaseor trypsin-based dissociation procedures, intraventricular adrenal medulla grafts, or remained with lesions alone. Rats with nigral or adrenal suspension grafts, but not rats with adrenal solid grafts, showed reduced apomorphine-induced rotation in comparison with lesion rats. The nigral graft group alone showed substantial reduction of amphetamine-induced rotation, and this was the only group manifesting good long-term graft survival. These results indicate that nigral and adrenal grafts do not have comparable mechanisms of functional action, and suggest that adrenal grafts can ameliorate apomorphine-induced rotation by a non-specific mechanism.
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  • 110
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    Naunyn-Schmiedeberg's archives of pharmacology 340 (1989), S. 239-245 
    ISSN: 1432-1912
    Keywords: Intestinal absorption ; Vascular perfusion ; Glucuronidation ; 1-Naphthol ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using the isolated vascularly fluorocarbon emulsion perfused rat small intestine some factors which determine the extent of the intestinal glucuronidation of 1-naphthol to 1-naphthol-β-d-glucuronide were studied. Increasing the luminal 1-naphthol concentration resulted in a concomitant increase in the 1-naphthol appearance in the vascular perfusate. In contrast, the total appearance of 1-naphthol-β-d-glucuronide increased less than proportional to the increase in the luminal 1-naphthol concentration. About 88% of the total amount of 1-naphthol-β-d-glucuronide excreted was released into the vascular perfusate. The capacity-limited intestinal glucuronide efflux is most likely due to saturation of the excretory mechanism for 1-naphthol-β-d-glucuronide. Decreasing the vascular flow rate influenced both the appearance of 1-naphthol and 1-naphtol-β-d-glucuronide in the vascular perfusate, whereas the appearance of 1-naphthol-β-d-glucuronide in the luminal perfusate was essentially flow-independent. A noradrenaline-induced change in the haemodynamic state of the vascular bed (with the total flow kept constant) resulted in a marked decrease in the 1-naphthol vascular concentration. The vascular 1-naphthol-β-d-glucuronide concentration was only slightly affected. These results indicate that changes in blood flow and blood flow distribution within the intestinal wall can affect the extent of presystemic intestinal metabolism by interfering with the absorption of the parent compound and the efflux of formed conjugates. These parameters can be of paramount importance for causing variable intestinal first-pass effects of drugs in vivo.
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  • 111
    ISSN: 1432-1912
    Keywords: Intestinal absorption ; 1-Naphthol ; Glucuronidation ; Rat ; Albumin binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using an isolated vasculary perfused rat small intestine we studied the role of luminal flow rate and intraluminal binding on the absorption of 1-naphthol (1-N) and the intestinal metabolism of 1-N to 1-naphthol-β-d-glucuronide (1-NG). Raising the luminal perfusion rate resulted in a decrease in the luminal 1-N extraction ratio and an increase in the luminal 1-N clearance Cl lum. The dependency of Cl lum on flow rate appeared to conform to a convective diffusion model. A differential susceptibility of 1-N absorption and the total 1-NG appearance to the luminal flow rate resulted in a flow-dependent first-pass effect of 1-N. Next, the effect of intraluminal binding on 1-N disposition was studied in experiments in which albumin was added to the luminal perfusion fluid. The unbound concentration, as the driving force for the uptake of 1-N, seems not to be rate-limiting for the appearance of 1-NG. The total appearance of 1-NG in the presence of albumin was greater than would be anticipated from the free concentration of 1-N. As a result the extent of presystemic extraction increased with increasing albumin concentration. The precise mechanisms responsible for the phenomenona are not entirely clear. Consideration of the heterogeneity in the glucuronidation capacity along the rat small intestine and along the crypt-villus axis can help to explain the obtained results.
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  • 112
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    Springer
    Pflügers Archiv 413 (1989), S. 217-224 
    ISSN: 1432-2013
    Keywords: Rat ; Kidney ; Uptake ; Transport ; α-Ketoglutarate ; Luminal ; Basolateral ; Production
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to establish the characteristics of net renal transport and utilization of α-ketoglutarate (α-KG) in the rat, we have precisely quantified the renal blood flow, the urinary flow and the rates of α-KG delivery, filtration, reabsorption or secretion, excretion, uptake or production by an in vivo rat kidney preparation. In normal rats, α-KG uptake was higher than α-KG reabsorption at both endogenous and elevated plasma α-KG concentrations; thus, a net peritubular transport, which was the main supplier of α-KG to the renal cells, took place. Saturation of reabsorption and peritubular transport of α-KG occurred at blood α-KG concentrations about 30 and 150 times above normal, respectively. Acute metabolic acidosis was found to have no effect on renal handling of α-KG. At endogenous plasma α-KG concentrations, alkalosis converted net renal uptake into net renal production of α-KG resulting in addition of α-KG by the renal cells both to blood and to the luminal fluid. Elevation of blood α-KG concentration restored the renal uptake of α-KG. This uptake, which was entirely accounted for by the peritubular transport of α-KG, reached a maximum which was lower than that observed in normal and acidotic rats.
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  • 113
    ISSN: 1432-2013
    Keywords: Rat ; Skeletal muscle ; Development ; Ionic conductances ; Denervation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The development of membrane ionic conductances of rat extensor digitorum longus (EDL) muscle fibers was studiedin vitro using intracellular recordings. At 7–8 days after birth, the potassium conductance (GK) dominated the total membrane conductance while the chloride conductance (GC1) was very low. A rapid increased of GC1 towards adult values was observed after few days (12–14 day old rats), whereas GK did not decrease up to day 23. Denervation at 7–8 days after birth suppressed the maturation of the electrical parameters measured, and 15 days after the nerve crush, GC1 was just detectable. These results suggest that the maturation of the electrical properties, and in particular that of the resting chloride conductance in mammalian striated muscle fibers, occurs during the first weeks of postnatal life and is dependent on innervation.
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  • 114
    ISSN: 1432-2013
    Keywords: Amiloride ; Bumetanide ; Cl-secretion ; Electrical field stimulation ; Large intestine ; Na-absorption ; Rat ; Stripping ; Submucosal plexus ; Tetrodotoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The initial phase of in vitro experiments in Ussing-type chambers on large intestine is characterized by short-circuit currents (ISC) declining from high starting values to a lower plateau within 0.5 h. The origin of this “initial ISC-transient” was investigated by ISC measurements on partially stripped segments of rat rectal colon. Transport was pre-stimulated in vivo by keeping animals in barbiturateanesthesia for 5 h prior to tissue preparation. This procedure caused by endogenous aldosterone-liberation amiloride-sensitive Na-absorption to become the predominant electrogenic transport. The initial ISC-transient was abolished by tetrodotoxin (TTX, 1 μM), indicating a neuronal mediation of this phenomenon. In order to identify the transport which was subject to neuronal control, the amiloride-sensitive Na-absorption was measured during electrical field stimulation (bipolar rectangular pulses: 5 Hz, 1 ms, ±6 mA). There was no difference to unstimulated controls. In contrast, the initial ISC-transient was dependent on Cl in the bath following Michaelis-Menten-kinetics (K M=20 mM) and could be prevented by 10 μM serosal bumetanide. Then, initial filling of the Ussing-chamber was imitated during the course of the experiment by removal and immediate readdition of the bathing fluid. This procedure caused ISC-changes of similar appearance as the initial ISC-transient. To verify that indeed mechanical stretch is the sensory stimulus triggering the initial ISC-transient, the effect of small pressure oscillations was studied. This also produced an ISC-transient which was TTX-sensitive and was abolished after removal of the submucosal plexus Meissner by total stripping. It is concluded that amiloride-sensitive Na-absorption does not contribute to the initial transient and is not affected by the enteric nervous system. Initial ISC-transients asobserved during the first half hour of Ussing experiments are due to electrogenic Cl-secretion which is stimulated by mechanical stretch during tissue preparation and filling of the chamber via a submucosal neuronal reflex pathway. The possible biological meaning of this stretch-induced secretory process could be facilitation of transit during imminent stasis of the gut contents.
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  • 115
    ISSN: 1432-2013
    Keywords: Fast-twitch muscle ; Chronic stimulation ; Contractil properties ; Parvalbumin ; Sarcoplasmic reticulum ; Ca2+-uptake ; Rat ; Rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study compares changes in contractile properties, Parvalbumin content, and Ca2+-uptake by the sarcoplasmic reticulum (SR) of low-frequency stimulated rat and rabbit tibialis anterior (TA) muscles. Time to peak tension increased 1.8-fold in 35-day stimulated rabbit TA, while no change occurred in rat TA. Isometric twitch tension increased 2-fold in rabbit TA, but was unaltered in rat TA. Parvalbumin (PA) content was more than 90% reduced in rabbit TA, but only 60% in rat TA after 35 days. At this time, PA content of the stimulated rat TA was still higher than that of normal rabbit TA. Taking into account the suggested role of PA as a cytosolic Ca2+ buffer, its decrease could lead to an impaired free Ca2+-decay with a prolonged active state and a higher tension output during a single twitch. This would explain why chronic stimulation led to an increase in isometric twitch tension in rabbit TA, but not in rat TA. The 1.6-fold rise in half-relaxation time of 35-day stimulated rat and rabbit TA most likely resulted from a 50% reduced Ca2+-uptake by the SR, due to a still unknown modification of the Ca2+-transport ATPase.
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  • 116
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    Pediatric nephrology 3 (1989), S. 149-155 
    ISSN: 1432-198X
    Keywords: Cationized bovine serum albumin ; Glomerular capillary wall polyanion ; Serum sickness glomerulopathy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of injected native and cationized bovine serum albumin (BSA− and BSA+ respectively) were evaluated in rats which subsequently received anti-BSA. Thrombocytopenia, low creatinine clearance (Ccr), increased proteinuria, capillary swelling, mild tuft necrosis and BSA+ deposits in glomeruli resulted within 24 h of BSA+ injection. Later BSA+ produced mesangial expansion glomerular capillary wall (GCW) thickening and deposits of BSA+ accompanied by rabbit anti-BSA and rat anti-BSA which correlated well with small mesangial, subendothelial and subepithelial electron-dense granular accumuli. These latter enlarged considerably after the injection of anti-BSA. BSA− controls showed minimal or no lesions. The disappearance from the blood (t1/2) of a single dose of immune complexes (IC) prepared with chromatography-purified, radioiodinated anti-BSA-BSA− and BSA+ was determined in another group of rats. The t1/2 of BSA− anti-BSA was 42.8 h (95% confidence: 39.8–46.2) while that of BSA+ anti-BSA was 52.5 h (48.1–57.8). These results suggested that serum sickness glomerulitis developed only in rats injected with BSA+, due to in situ IC which presumably grew by accretion of foreign anti-BSA. Circulating IC may have developed and colocated with the latter, with dissociation and recombination at these sites. It is postulated that the functional-immunomorphological changes and the slow removal of cationized IC reported herein could be explained by the highly positive net charge of the injected antigen.
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  • 117
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    Psychopharmacology 97 (1989), S. 35-39 
    ISSN: 1432-2072
    Keywords: Delta-sleep-inducing peptide (DSIP) ; Paradoxical sleep (PS) ; Phosphorylated analogue of DSIP ; Rat ; Sleep substance ; Slow wave sleep (SWS)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Continued 10-h nocturnal intracerebroventricular infusion of 0.5 nmol P-DSIP, the phosphorylated analogue of delta-sleep-inducing peptide (DSIP), significantly increased slow wave sleep (22%) and paradoxical sleep (81%) in unrestrained rats. The increase in the amount of sleep was largely due to an increase in the number of sleep episodes. Larger and smaller doses were ineffective in doses ranging from 0.025 to 25 nmol. The sleep-promoting potency of P-DSIP was 5 times greater than that of DSIP compared by the same assay.
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  • 118
    ISSN: 1432-2072
    Keywords: Social memory ; Cholinomimetic drugs ; Nootropic drugs ; Benzodiazepine inverse agonists ; Psychostimulants ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The recognition of an unfamiliar juvenile rat by an adult rat has been shown to imply short-term memory processes. In this study the effect of various psychotropic drugs on this investigatory behaviour was examined. The procedure was as follows: an unfamiliar juvenile rat was placed in the home cage of an adult rat for 5 min. The time spent by the adult rat in investigating the juvenile was recorded. The adult rat was then immediately treated with vehicle or test compounds, and was again exposed for 5 min to the same juvenile 2 h later. At this time point vehicle-treated rats no longer recognized the juvenile rat, i.e. the time of investigation was similar to that observed during the first presentation. Arecoline (1 and 3 mg/kg IP), physostigmine (0.05 and 0.1 mg/kg SC), RS86 (0.5 mg/IP) and nicotine (0.125 and 0.5 mg/kg IP) reduced in a dose-dependent fashion the time spent in investigating the juvenile during the second exposure. This result cannot be attributed to nonspecific effects, since it was not observed when a different juvenile was used for the second exposure. The effect of arecoline was reversed by scopolamine, but not by methylscopolamine. Aniracetam reduced investigatory behaviour at the dose of 50 mg/kg IP. FG 7142 (5 mg/kg IP) and β-CCM (0.4 mg/kg IP) were also active and their effect was reversed by Ro 15-1788. dl-Amphetamine (0.5 and 1 mg/kg IP), nomifensine (1.25–10 mg/kg IP) and strychnine (0.25 and 0.5 mg/kg IP) were ineffective or reduced this behaviour unspecifically. Social recognition may therefore represent a useful and simple test to detect compounds which enhance short-term, olfactory, memory and to assess in the same animals the specificity of this activity.
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  • 119
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    Psychopharmacology 97 (1989), S. 521-528 
    ISSN: 1432-2072
    Keywords: Trimethyltin ; Delay conditioning ; Conditioned flavor aversion ; Passive avoidance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Trimethylin (TMT) produces behavioral and cognitive deficits resulting, in part, from limbic system toxicity. To determine whether these effects result from learning deficits or accelerated memory loss, the present experiment examined two delay conditioning paradigms in rats previously treated with either saline or TMT. Saline-treated Long-Evans rats receiving injections of lithium after consuming saccharin-flavored water later avoided saccharin ingestion: the degree of avoidance varied inversely with the time (0.5, 3 or 6 h) separating initial saccharin availability and lithium injection. Rats treated with TMT (8 mg/kg IV, 30 days prior) showed impaired conditioning at the long but not the short or intermediate delay conditions, suggesting that the deficits were mnemonic and not associative. Similar delay-dependent deficits in rats treated with TMT were observed in a passive avoidance task that arranged one of two delays between response emission and shock delivery during training. The effects of TMT on delay conditioning were accompanied by reduced bodyweight and hippocampal pathology. In summary, TMT appears to alter the temporally dependent association of events (entering darkened compartment versus saccharin consumption) and consequences (foot shock versus lithium administration) during acquisition. Furthermore, the observed deficits in delay conditioning produced by TMT did not appear to be task specific, with similar effects determined with tests of both somatosensory and gustatory avoidance learning designed to distinguish between functional alterations due to deficits in memorial processes from those due to altered sensory, motor, or associative processes.
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  • 120
    ISSN: 1432-2072
    Keywords: Anxiety ; Social interaction ; Plus-maze ; 5HT3 receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of three 5HT3 receptor antagonists: BRL 43964 (0.1 and 1 mg/kg, oral), GR 38032F (0.1 and 1 mg/kg, oral), and zacopride (0.01, 0.1 and 1 mg/kg, IP) were examined in low light test conditions of the social interaction test. None of the three 5HT3 receptor antagonists had a significant effect on social interaction. In contrast, in two experiments chlordiazepoxide (7.5 mg/kg) significantly increased social interaction and this effect was greatest in the unfamiliar test condition. In a third experiment, the effects of GR 38032F (0.1 and 1 mg/kg, oral) and zacopride (0.01, 0.1 and 1 mg/kg, oral) were investigated in the high light test conditions of the social interaction test; neither compound had a significant effect. In the elevated plus-maze, chlordiazepoxide (7.5 mg/kg oral or IP) significantly increased both the per cent number of entries made onto open arms and the per cent of time spent on the open arms, indicating an anxiolytic action. Zacopride (0.01, 0.1 and 1 mg/kg, oral or IP) had no significant effect in this test. The effect of the baseline rate of responding in the social interaction test on the effects of 5-HT3 antagonists is discussed. The results from the present experiment and those from other animal tests of anxiety caution against the conclusion that 5HT3 receptor antagonists are anxiolytic.
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  • 121
    ISSN: 1432-2072
    Keywords: Apomorphine ; Dopamine ; Penile reflex ; Sexual behavior ; Spinal cord ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Relatively high doses of systemically administered apomorphine inhibit penile reflexes. It is possible that these inhibitory effects are due, at least in part, to actions of apomorphine on the lumbosacral spinal cord. The present experiments examined this possibility by injecting apomorphine (10 and 50 μg/5.0 μl vehicle) into the lumbosacral subarachnoid space through chronic, indwelling cannulae. Such injections impaired ex copula penile reflexes, slowed the rate of copulation, and decreased the number of intromissions preceding ejaculation. These results suggest that lumbosacral cord dopamine receptors may normally regulate male sexual performance.
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  • 122
    ISSN: 1432-2072
    Keywords: Riluzole ; FG 7142 ; β-Carboline ; Anxiety ; Conflict procedures ; Animal model ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The possible anxiolytic activity of riluzole, a drug which interferes with glutamic acid neurotransmission, was studied in rats using operant conflict procedures. In both “anxiolytic” and “anxiogenic” procedures, riluzole alone did not possess any anticonflict or proconflict effect at doses of 2 and 4 mg/kg PO. Riluzole over the same dose-range was able to antagonize the well known proconflict effect of the β-carboline derivative FG 7142, an inverse agonist at the GABA-benzodiazepine-chloride ionophore receptor complex. This effect could be related to the possible interaction of riluzole with glutamic acid neurotransmission, since it has been demonstrated previously that β-carbolines such as DMCM and β-CCM were able to deplete the levels of aspartic and glutamic acids in rodent cortex, perhaps by enhancing release of amino acid neurotransmitters. If one subscribes to the hypothesis that the anxiety induced by β-carboline derivatives is related to depression, riluzole might be of value in the treatment of anxiety related to depression.
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  • 123
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    Psychopharmacology 97 (1989), S. 175-178 
    ISSN: 1432-2072
    Keywords: Serotonin ; Morphine ; Nicotine ; Amphetamine ; Reward ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of two potent and specific antagonists of 5HT3 receptors, ICS 205-930 and MDL 72222, on the reinforcing properties of amphetamine, morphine and nicotine was studied in rats. Durg-induced reinforcement was assessed by measuring drug-conditioned place preference. ICS 205-930 and MDL 72222 dose-dependently reduced the place preference induced by morphine (1.0 mg/kg SC). At doses of 0.030 mg/kg SC the two antagonists completely blocked morphine-induced place preference while doses of 0.015 mg/kg SC significantly reduced it. ICS 205-930 and MDL 72222 at doses of 0.030 mg/kg SC also prevented the place preference induced by nicotine (0.6 mg/kg SC). In contrast, ICS 205-930 and MDL 72222 up to doses of 0.030 mg/kg SC failed to modify the place preference elicited by amphetamine (1.0 mg/kg SC). The results indicate that 5HT3 receptors are specifically involved in the reinforcing properties of morphine and nicotine.
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  • 124
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    Psychopharmacology 97 (1989), S. 206-212 
    ISSN: 1432-2072
    Keywords: LSD-cue ; Drug discrimination ; Risperidone ; Schizophrenia ; 5-HT2-catecholamine antagonism ; LSD antagonism ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Risperidone was studied in a 0.16 mg/kg LSD-saline drug discrimination test procedure. At doses varying from 0.0025 to 0.63 mg/kg, no LSD-like agonist effects were observed. Studies on the antagonism of the LSD-cue indicated that risperidone was able to completely block the discriminative stimulus properties of LSD with a minimum ED50-value of 0.028 mg/kg. Risperidone was also very active over time with reference to LSD antagonism, the ED50s after 2, 4 and 8 h pretreatment being 0.028, 0.064 and 0.44 mg/kg. Response rate reductions were only observed at doses ≧0.16 mg/kg after 1 h and at 0.63 mg/kg after 2 h pretreatment. Four and 8 h after treatment, no rate-reducing effects were apparent at doses up to 2.50 mg/kg. Thus at pretreatment intervals ranging between 2 and 8 h, complete antagonism of LSD without any rate effects was obtained. As compared to other LSD antagonists, risperidone was quantitatively better than setoperone and ritanserin and longer acting than pirenperone. Based on the pharmacological profile of risperidone and the other LSD antagonists, it was concluded that a potent central 5-HT2 and catecholamine antagonism is needed for a potent and complete antagonism of the 0.16 mg/kg LSD-cue. The potential clinical effect of risperidone in the positive and negative symptoms of schizophrenia is discussed.
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  • 125
    ISSN: 1432-2072
    Keywords: Rat ; Operant behavior ; Fixed-interval ; Ventral tegmental area ; Neurotensin ; Substance P ; Neurokinin-α (substance K) ; d-Ala-Met-enkephalin ; Dopamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The neuropeptides neurotensin, substance P, neurokinin-α (substance K), and met-enkephalin are present endogenously in the ventral tegmental area (VTA), site of the A10 dopaminergic (DA) cell bodies. In the present study these four peptides were injected bilaterally into the VTA in the rat, and the effects on operant behavior were assessed. Cannulae aimed at the VTA were implanted in four groups of animals, which had been trained to bar-press for food reward on a fixed-interval, 40-s schedule. A fifth group, in which the effects of systemically administered amphetamine were assessed, was also tested. Response rate across the interval was measured, and the index of quarter-life was taken as an indication of the temporal pattern of resonding. In addition, a rate-dependency analysis was carried out for all data. Neurotensin (NT, 0.0175, 0.175, 0.5 μg in 1 μl) dose-dependently decreased response rates without affecting quarter-life, and reduced the number of reinforcements obtained. Substance P (SP, 0.1, 1.0, 3.0 μg) did not affect responding, and neurokinin-α (NKA, 0.1, 1.0, 3.0 μg) induced a small increase in responding. Quarter-life was not affected by SP or NKA, but responding on the nonreinforced lever was significantly increased by both peptides. d-Ala-met-enkephalin (DALA, 0.01, 0.1, 1.0 μg) induced a dose-dependent increase in responding which was also rate-dependent, and reduced quarter-life. DALA effects were similar to the classic pattern of responding observed after systemic amphetamine. These results suggest that although all these peptides elicit behavioral activation and may affect DA neuronal activity, the behavioral responses can be differentiated with respect to operant behavior.
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  • 126
    ISSN: 1432-2072
    Keywords: Sleep ; 5-Hydroxytryptamine (5-HT) ; Antagonist ; Agonist ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recently developed agents specifically acting on different 5-hydroxytryptamine (5-HT) receptor populations were used to analyze the functional role of 5-HT2 receptor subtypes in the sleep-wakefulness cycle of the rat. The 5-HT2 receptor antagonist ritanserin injected intraperitoneally (IP) (0.04–2.5 mg/kg) induced an increase in deep slow wave sleep (SWS2) duration at the expense of wakefulness (W), light slow wave sleep (SWS1) and paradoxical sleep (PS). The stimulation of 5-HT2 receptors by 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) produced a dose-related increase in W and a dose-dependent decrease in both SWS2 and PS. Pretreatment with ritanserin (0.16–2.5 mg/kg) or with cinanserin (2.5–5 mg/kg), another 5-HT2 receptor antagonist, dose-dependently reversed the W enhancement and the SWS2 deficit produced by DOM, but not the PS deficit. Sleep-wakefulness alterations (increase in W and SWS1 combined with a suppression of SWS2 and PS) observed after IP injection of two putative 5-HT1 receptor agonists, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (2.5 mg/kg) and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU 24969) (0.63 mg/kg), were not modified by ritanserin pretreatment (0.16–2.5 mg/kg). These results further support the hypothesis that the serotonergic system plays an active role in the regulation of the sleep-wakefulness cycle in the rat and that 5-HT2 receptors are involved in this action. In addition it is suggested that 5-HT1 receptor subtypes are unlikely to interact with 5-HT2 receptors in the sleep-wakefulness modulation mediated through 5-HT2 receptors.
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  • 127
    ISSN: 1432-2072
    Keywords: Amygdala ; Benzodiazepine ; GABA ; Barbiturates ; Conflict ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to elucidate the role of the amygdala in rat conflict behavior in a water lick suppression test, we examined the effect of lesions of various nuclei of the amygdaloid complex on this behavior. An anticonflict effect was produced by a lesion of the anterior part of central and basolateral amygdala, and lesion to the posterior part of the central amygdala, but not by posterior of the basolateral amygdala or medial amygdala lesions. These results suggest that the amygdala, especially the anterior part of the central and basolateral nuclei, plays an important role in conflict behavior of rats in the water lick test. In a second experiment, the effects of benzodiazepine- and GABA-antagonists on the anticonflict action of diazepam, zopiclone, and phenobarbital injected into the anterior part of central and basolateral amygdala were examined, also using a water lick suppression test. A dose-dependent anticonflict action was produced by systemic administration as well as by intra-amygdala injection of diazepam, zopiclone, lormetazepam, flurazepam and phenobarbital. The order of potency was lormetazepam〉zopiclone≧diazepam〉flurazepam ≧phenobarbital for both routes of injection. The antiamygdala effects of diazepam and zopiclone injected into the amygdala were completely reversed by Ro15-1788 and β-CCM but not by bicuculline, while the anticonflict effect of phenobarbital was reversed by β-CCM but not by Ro15-1788 or bicuculline. The present results strongly suggest that the anterior nuclei of central and basolateral amygdala are important sites of action of antianxiety drugs, and that an anticonflict action produced by intra-amygdala injection of benzodiazepines or barbiturate is mediated through the different receptor mechansims.
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  • 128
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    Psychopharmacology 98 (1989), S. 61-67 
    ISSN: 1432-2072
    Keywords: Rat ; Place preference ; Extinction ; Conditioning ; Naloxone ; Heroin ; Clonidine ; Pimozide ; Memory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract These experiments examined the neurochemical mechanisms involved in the development and expression of place conditioning produced by heroin. Conditioned place preferences (CPP) lasting up to 8 weeks were obtained with doses of 50–1000 μg/kg heroin, using a regimen shown not to produce physical dependence. Naloxone pretreatment (50 μg/kg) during conditioning prevented the acquisition of heroin-induced CPP, but when given only on the test day, naloxone (50 or 1000 μg/kg) did not prevent the expression of heroin CPP. Clonidine disrupted the establishment of heroin CPP at 20 μg/kg, but disrupted its expression only at debilitating doses (100 and 200 μg/kg). Pimozide attenuated the acquisition (100 μ/kg) and expression (250 μg/kg) of heroin CPP. Together, these results support a role for opioid and catecholamine systems in the acquisition of heroin reinforcement, but they suggest that once heroin CPP is established, its expression in opiate-free subjects is not opiate receptor mediated and is relatively refractory to pharmacological treatments which disrupt acquisition. The data challenge the notion that the conditioned effects of opiates in drug-free animals are related to the release of endogenous opioids, and they also may help to explain why naloxone and clonidine are ineffective in the treatment of opiate addiction.
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  • 129
    ISSN: 1432-2072
    Keywords: LY 163502 ; Dopamine D-1 and D-2 receptors ; Jerking ; Behavioural assessment ; Stereotypy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The new, extremely potent and enantioselective D-2 agonist LY 163502 failed to induce compulsive stereotyped behaviour. Very low doses (3–6 μg/kg) inhibited spontaneous sniffing and locomotion, while higher doses (12–50 μg/kg) induced episodes of non-stereotyped sniffing and chewing; these actions showed complete enantioselectivity. Up to 200-fold higher doses modestly induced only locomotion. Responsivity to LY 163502 was enantioselectively blocked by the selective D-2 antagonist R-piquindone. This responsivity was also enantioselectively blocked by the selective D-1 antagonist R-SK&F 83566 but, additionally, episodes of atypical limb/body jerking behaviour were released; thus, LY 163502 induced such jerking only when tonic D-1 activity was suppressed. These data extend our notion that there may be at least two forms of functional interaction between D-1 and D-2 receptor systems: one cooperative, as in the regulation of typical sniffing, and another oppositional, as in the regulation of atypical jerking.
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  • 130
    ISSN: 1432-2072
    Keywords: Hallucinogenics ; Amphetamine ; Rat ; Tele-Stereo-EEG
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Telemetric recordings of field potentials from frontal cortex, hippocampus, striatum and reticular formation of freely moving rats were analysed before and after injection of the enantiomeric hallucinogenic amphetamine derivatives R-DOB [(−)-1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane], R-DOM [(−)-1-(2,5-dimethoxy-4-methylphenyl)-2-amino-propane] and R-DOI [(−)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropanel] as well as the nonhallucinogenic amphetamine derivatives S-MBDB [(+)-N-methyl-1-(1,3-benzodioxol-5-yl)butanamine] and S-MDMA [(+)-3,4-methylenedioxymethamphetamine] and S-(+)-amphetamine. The frequency analysis of the field potentials revealed a clearcut difference between them. The spectral patterns emerging after injection of the non-hallucinogens were characterized by a general decrease of power, the changes in the alpha2 and delta band being the most prominent, whereas only after the application of the hallucinogenic compounds was a contrasting increase of power observed in the alpha1 frequency band, especially in the striatum. As increases in alpha1 power have been correlated in the same pharmacological model to serotonergic control mechanisms, the results are in line with the hypothesis that 5-HT2 receptors, predominantly occurring in the striatum, might be involved in the hallucinogenic action of drugs.
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  • 131
    ISSN: 1432-2072
    Keywords: Haloperidol ; Dopamine ; Oral movements ; Rat ; Tardive dyskinesia ; Homovanillic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats with more severe orofacial movements after 51 days of haloperidol administration showed lower levels of the dopamine metabolite homovanillic acid (HVA) in the caudate compared to animals who did not develop significant mouth movements. This effect was not observed in other brain regions sampled. This finding is consistent with the hypothesis that dopaminergic receptor supersensitivity in neostriatal structures plays some role in the development of orofacial movements in rats, in association with chronic neuroleptic administration.
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  • 132
    ISSN: 1432-2072
    Keywords: SCH 23390 ; Catalepsy ; Tolerance ; Neuroleptics ; Rat ; Chronic treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The development of tolerance to the cataleptic effect of the selective D-1 antagonist SCH 23390 (0.5 mg/kg/day SC or 0.1 mg/kg/day SC) and haloperidol (1 mg/kg/day SC) during repeated administration was investigated. Catalepsy in rats was measured using the horizontal bar method. SCH 23390 induced a dose-related cataleptic effect of short duration, whereas the cataleptic effect of haloperidol appeared more slowly and lasted longer. Marked tolerance to the cataleptic effect of haloperidol developed already 6 days from the beginning of the treatment. The cataleptic effect of the higher dose regimen of SCH 23390 was also significantly reduced after 6 days' treatment. However, unlike haloperidol, this subacute tolerance was gradually reversed and was no longer significant after 12 and 18 days. The cataleptic response to the lower dose of SCH 23390 (0.1 mg/kg/day) was not significantly altered during the treatment and no initial catalepsy tolerance was observed with this dose regimen. These results suggest that different mechanisms are involved in the expression of cataleptic behaviour during chronic treatment with SCH 23390 and classical antipsychotics, such as haloperidol.
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  • 133
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    Psychopharmacology 99 (1989), S. 27-33 
    ISSN: 1432-2072
    Keywords: Corticotropin-releasing factor (CRF) ; Amphetamine ; Stereotypy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Corticotropin-releasing factor (CRF) is a 41-amino acid polypeptide that is critically involved in the activation of the hypothalamic-pituitary adrenal axis during stress. In addition, it has been suggested that extrahypothalamic CRF may be important in initiating behavioral responses to stressful events. In the present experiment, we examined the effects of central administration of CRF on amphetamine-induced stereotyped behavior. Amphetamine-induced stereotyped behavior has been considered as a behavioral strategy to cope with excessive arousal. Low doses of CRF (0.02 and 0.1 μg), administered into the lateral ventricle (ICV), were shown to potentiate amphetamine (4.0 mg/kg; SC)-induced stereotyped behavior, as measured by the Creese and Iversen rating scale and behavioral observations. These low doses of CRF specifically enhanced the tendency for rats to sniff with their heads down 20 min after injection, and induced licking behavior later during testing. In contrast, the rats treated with a higher dose of CRF (0.5 μg, ICV) showed more locomotor activity throughout the test, but did not differ from the saline-treated animals in the intensity of amphetamine-induced stereotyped behavior.
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  • 134
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    Psychopharmacology 99 (1989), S. 140-142 
    ISSN: 1432-2072
    Keywords: γ2-MSH ; Naloxone ; Opiate dependence ; Taste preference conditioning ; Taste aversion ; Withdrawal motivation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A two flavour, unbiased, taste preference conditioning procedure was used to test for possible motivating effects of γ2-MSH. Three training trials failed to produce any significant effect with doses ranging from 2.4 to 40 μg/ ICV infusion in drug-naive, non-operated or placebo-implanted rats. However, in rats made dependent by SC implantation of a morphine pellet 4 days earlier 15 μg γ2-MSH/infusion produced a taste aversion that was comparable to that produced by infusion of a low dose of the competitive opioid receptor antagonist naloxone (0.32 μg). The findings confirm with a conditioning procedure and with opiate-dependent animals the naloxone-like effects of γ2-MSH. They also suggest that this endogenously-located peptide may acquire an aversive property as a result of chronic morphine treatment.
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  • 135
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    Psychopharmacology 99 (1989), S. 270-275 
    ISSN: 1432-2072
    Keywords: Olfactory learning ; Rat ; Scopolamine ; Septal lesions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male rats were tested in a simple olfactory habituation and discrimination paradigm. Untreated rats habituated their responses over three trials to one odour but were capable of recognising a novel odour presented on the fourth trial. Administration (SC) of either scopolamine or N-methylscopolamine before trials commenced produced a decrease in overall responding. Scopolamine, but not N-methylscopolamine, also blocked habituation to the first odour and recognition to the second, novel odour. Administration of scopolamine after trial 3 did not block the ability of the animals to respond differentially to a novel odour, although again overall levels of responding were decreased. Electrolytic lesions of the medial septal area increased overall levels of responding but lesioned animals still habituated their response over trials and were capable of recognising a novel odour. Therefore although cholinergic mechanisms appear to be involved in this type of learning, these effects are unlikely to be mediated via the septohippocampal system.
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  • 136
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    Psychopharmacology 99 (1989), S. 352-356 
    ISSN: 1432-2072
    Keywords: Conditioned locomotion ; MDMA ; Aniphetamine ; Cocaine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Daily administration of a drug in a distinctive environment establishes contingencies that support Pavlovian conditioning. Environmental cues that are paired with the drug injection and that predict the onset of drug action can become conditioned stimuli. Ultimately, the conditioned stimuli come to predict the availability of drug and develop the potential to engender conditioned drug responses. Various psychostimulant drugs can produce conditioned locotnotion when tested in the presence of environmental cues that were repeatedly associated with the drug experience. The ability of amphetamine and cocaine to produce conditioned locomotion was demonstrated in the present study. Stimulant-like properties of methylenedioxymethamphetamine (MDMA) have been reported in locomotor paradigms, drug discrimination procedures, and human subjective questionnaires. MDMA (5 mg/kg), paired for 5 days to a distinct environment signalled by the presence of a distinct odor, produced enhanced locomotion during a test probe with the odor alone indicating that MDMA can also produce conditioned locomotion. The observation that the stimulus properties of MDMA can also become associated with environmental cues supports the hypothesis that some of the behavioral effects of MDMA resemble those of other classical psychostimulants such as amphetamine and cocaine.
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  • 137
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    Psychopharmacology 99 (1989), S. 366-370 
    ISSN: 1432-2072
    Keywords: Ethanol tolerance ; Intoxicated practice ; Motor impairment ; Hypothermia ; Narcosis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The development of tolerance to the motor impairment effect of ethanol was examined in separate groups of rats receiving and not receiving intoxicated practice. Tolerance to the motor impairment effect of ethanol developed whether or not rats received intoxicated practice during chronic ethanol treatment. Depending on the treatment dosage and test dose, intoxicated practice might enhance the level of tolerance attained. Tolerance to other effects of ethanol (hypothermia and narcosis) developed as a function of the treatment dosage. Intoxicated practice on the moving belt did not modify the development of tolerance to these effects of ethanol. Tolerance to the motor impairment effect of ethanol, however, was retained much longer in the intoxicated practice group following the termination of ethanol treatment.
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  • 138
    ISSN: 1432-2072
    Keywords: Thermoregulation ; Acetylcholine ; Muscarinic ; Serotonin ; Interaction ; Alaproclate ; Oxotremorine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Stimulation of muscarinic cholinergic receptors with the highly potent and selective receptor agonist oxotremorine produced hypothermia in rats. Alaproclate, a purported selective serotonergic reuptake inhibitor, potentiated this response. Destruction of central presynaptic serotonergic terminals with the potent cytotoxin p-chloroamphetamine (PCA) failed to attenuate the hypothermic response to oxotremorine in alaproclate-pretreated animals. These results could be taken to suggest that alaproclate may act, at least in part, via a non-serotonergic mechanism to potentiate the oxotremorine-induced hypothermic response.
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  • 139
    ISSN: 1432-2072
    Keywords: Neuropeptide Y ; Anxiolysis ; Conflict model ; Alpha-adrenergic ; Idazoxan ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Effects of intracerebroventircular (ICV), neuropeptide Y (NPY) (0.2–5.0 nmol) and its C-terminal 13–36 amino acid (AA) fragment (0.4–2.0 nmol) have been examined with respect to anxiolytic properties in two rat anxiety models, Montgomery's conflict test (MT), and Vogel's drinking conflict test (VT). In the MT, 1.0 and 5.0 nmol NPY abolished the normal preference for the closed arms of the maze. At 5.0 nmol, the total number of entries made into both closed and open arms was decreased by 50%. In the VT, both 0.2 and 1.0 nmol NPY markedly increased the number of shocks accepted. The effect of 5.0 nmol NPY was less pronounced. In control experiments, NPY (0.2 nmol) did not affect pain sensitivity or thirst. Pretreatment with the selective alpha2-adrenergic receptor antagonist idazoxan, at a dose which by itself did not affect behaviour (2.0 mg/kg), antagonized the effect of 1.0 nmol NPY in the VT. NPY 13-36 was without significant effect in both models. The results suggest that NPY exerts anxiolytic-like effects, and that these effects are mediated through an interaction with noradrenergic systems. Higher doses of NPY produce sedation and ataxia, which decrease overall activity in the MT, and interfere with the ability fully to express behaviourally the anxiolytic-like effect in the VT. The findings are discussed in relation to the noradrenaline hypothesis of anxiety, and to observations indicating involvement of NPY in the pathophysiology of major depression.
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  • 140
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    Psychopharmacology 97 (1989), S. 466-470 
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Benzodiazepine ; Midazolam ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats (N=12) were trained to discriminate midazolam (1 mg/kg, IP) from vehicle in a food reinforced operant conditioning procedure. Midazolam, flunitrazepam, diazepam, chlordiazepoxide and pentobarbital showed dose-dependent substitution for midazolam. Buspirone and Ro 15-1788 did not substitute for midazolam. The midazolam cue was dose-dependently antagonized by Ro 15-1788. In rats (N=12) trained to discriminate chlordiazepoxide (3 mg/kg, IP) from vehicle midazolam, flunitrazepam, diazepam and chlordiazepoxide substituted completely and dose dependently for chlordiazepoxide. The relative potency of chlordiazepoxide and diazepam was three times less in the midazolam-trained animals than in the chlordiazepoxide-trained animals. Response rate and latency data further support the main finding that the midazolam cue is similar, but not identical to the cue of classical benzodiazepines.
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    Psychopharmacology 99 (1989), S. 362-365 
    ISSN: 1432-2072
    Keywords: Acoustic startle reflex ; Fear-conditioning ; Midazolam ; DMCM ; Lindane ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Forty-eight male Wistar rats were exposed to contingent light-shock combinations and 48 rats received light and shock stimuli in a random order. One day after fear conditioning the animals were tested for startle potentation after injection of midazolam (0, 0.5, 1.0, 2.0 mg/kg, IP) or DMCM (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; 0, 0.1, 0.2, 0.4 mg/kg IP) or lindane (0, 7.5, 15.0, 30.0 mg/kg PO). Midazolam attenuated potentiated startle dose dependently and the inverse benzodiazepine agonist DMCM had the opposite effect. The effects of lindane on startle amplitudes were identical to those of DMCM, indicating that lindane has anxiogenic effects on behavior. It is suggested that the anxiogenic effects of lindane are mediated by an effect at the GABA-ionophore complex.
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    Psychopharmacology 99 (1989), S. 402-408 
    ISSN: 1432-2072
    Keywords: Feeding ; 8-OH-DPAT ; Dopamine ; Antagonists ; Grooming ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Feeding elicited by the 5HT1A agonist 8-OH-DPAT was blocked by pretreatment with the DA antagonists SCH-23390 and sulpiride, in two experiments conducted in non-deprived rats and in three experiments conducted after 4 h food deprivation. In deprived animals, 8-OH-DPAT prolonged the initial period of feeding. However, in non-deprived animals, 8-OH-DPAT delayed the onset of eating, and suppressed post-prandial resting; both SCH-23390 and sulpiride restored the normal pattern of behaviour. All three drugs suppressed grooming. The results suggest that 8-OH-DPAT elicits feeding by a secondary disinhibition of activity postsynaptic to DA neurons. The consequences of this mechanism for the interpretation of 8-OH-DPAT-induced feeding are discussed.
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  • 143
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    Psychopharmacology 98 (1989), S. 203-206 
    ISSN: 1432-2072
    Keywords: Place conditioning ; Motivation ; Aversion ; Opioids, μ-, δ- and κ-receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of central versus peripheral opioid receptors in mediating the aversive effects of opioids was examined by use of an unbiased place preference conditioning procedure in rats. The non-selective opioid antagonist naloxone (NLX) produced conditioned aversions for the drug-associated place after subcutaneous (SC) as well as intracerebroventricular (ICV) administration. Place aversions were also observed in response to the ICV administration of the selective μ-antagonist CTOP. In contrast, the selective δ-antagonist ICI 174,864 and the selective κ-antagonist norbinaltorphimine (nor-BNI) (ICV) were without effect. Place aversions were also produced by central applications of the selective κ-agonist U50,488H and the dynorphin derivative E-2078. For those opioid ligands tested, the doses required to produce place aversions were substantially lower following ICV as compared to SC administration. These data confirm that κ-agonists and opioid antagonists produce aversive states in the drug-naive animal and demonstrate that this effect is centrally mediated. Furthermore, the ability of NLX and CTOP, in contrast to both ICI 174,864 and nor-BNI, to produce place aversions suggests that the aversive effects of opioid antagonists result from the blockade of μ-receptors.
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  • 144
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    Psychopharmacology 98 (1989), S. 530-534 
    ISSN: 1432-2072
    Keywords: Morphine ; Opiates ; Dependence ; Nucleus accumbens ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies from our laboratory using methylnaloxonium, a hydrophilic antagonist, showed that opiate receptors in the region of the nucleus accumbens are important for the acute reinforcing effects of heroin in non-dependent rats. A similar increased sensitivity to the response disruptive effects of intracerebrally injected methylnaloxonium in opiate dependent rats was observed in a fixed-ratio (FR) baseline of operant behaviors. These results suggest that the same opiate receptors in the region of the nucleus accumbens important for the positive reinforcing stimulus properties of opiates may also be responsible for the response disruptive, aversive stimulus properties of opiate withdrawal. These results also suggest that the neural substrates of some aspects of dependence may be partly related to those of the reinforcing effects of opiates. In particular, it is hypothesized that “euphoria” and “dysphoria” induced by opiates may reflect opponent motivational processes operating at a cellular level within the nucleus accumbens.
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  • 145
    ISSN: 1432-2072
    Keywords: Cocaine ; Dopamine ; Dopamine receptors ; Drug discrimination ; Drug stimuli ; Receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The involvement of dopamine (DA) receptor subtypes in the behavioral effects of CNS stimulants was studied in rats trained to discriminate occaine from saline. In substitution tests, the stimulus effects of 10mg/kg of this substance generalized tod-amphetamine (0.25–1.0 mg/kg) and the selective D2 against LY-171555 (0.05–0.25 mg/kg); but not to the D1 agonist SKF-38393 (5.0–15.0 mg/kg); in combination tests, the D1 antagonist Sch-23390 (0.0625–0.5 mg/kg) significantly blocked, and the D2 antagonist spiperone (0.25–0.5 mg/kg) partially blocked the cocaine cue. These data suggest that the involvement of DA systems in the behavioral effects of cocaine is more complex than either D1 or D2 receptor activation; for example, the stimulus properties of this substance might involve both D1 and D2 receptor activation.
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  • 146
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    Psychopharmacology 99 (1989), S. 87-90 
    ISSN: 1432-2072
    Keywords: Glutamate ; Kainate ; Ketamine ; Kynurenic acid ; MK-801 ; NMDA ; Phencyclidine ; Rat ; Self-stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract MK-801 is a ligand at phencyclidine recognition sites associated with NMDA-coupled cation channels, where it acts as a potent noncompetitive antagonist of central glutamate/aspartate (NMDA-type) receptors. Low doses (10–100 μg/kg IP) produced a dose-related and prolonged (〉1 h) enhancement of variable-interval self-stimulation responding. Higher doses (300 μg/kg) caused flaccid ataxia and disrupted responding. Ketamine HCl (3.0–100 mg/kg IP), a dissociative anaesthetic binding to the phencyclidine site, produced a similar response pattern, but facilitation was less prolonged and occurred over a narrower dose range. Kynurenic acid (3.0–300 mg/kg IP), a nonselective competitive antagonist of glutamate receptors, produced only depression of responding, possibly the result of kynurenate-induced blockade of central kainate and/or quisqualate receptors. The behavioural stimulant effects of MK-801 appear to be an intrinsic and essential feature of selective NMDA antagonists, and these effects of MK-801 differ qualitatively and quantitatively from the well-known facilitatory effects of dopamine-dependent stimulants.
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  • 147
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    Psychopharmacology 99 (1989), S. 98-102 
    ISSN: 1432-2072
    Keywords: Sucrose preference ; Two-bottle test ; Dopamine ; Sulpiride ; SCH-23390 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Effects of the dopamine D2 receptor antagonist sulpiride and the D1 antagonist SCH-23390 were examined, in rats, in two-bottle preference tests (sucrose versus water) and in single-bottle tests, at different sucrose concentrations. Both drugs decreased sucrose intake in single bottle tests, at low sucrose concentrations, but had no effect at high concentrations; reducing drive level had exactly the opposite pattern of effects. In two-bottle tests, both drugs reduced preference for the weakest sucrose concetration (0.7%) but increased preference for the strongest concentration (34%). The effects of antagonizing either subtype of DA receptor appear to be similar to those of reducing the concentration of sucrose.
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  • 148
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    Psychopharmacology 99 (1989), S. 316-321 
    ISSN: 1432-2072
    Keywords: Aging ; Phosphatidylserine ; Spatial memory ; Passive avoidance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Learning/memory deficits in senescent animals are widely used as a tool to evaluate the therapeutic potential of agents for treatment of age-associated cognitive dysfunction. As assessed in the Morris water maze test, aged (21–24 months) rats showed a variable loss of spatial memory. Aged non-impaired rats performed as well as young subjects, while aged impaired rats exhibited a severe and persistent place-navigation, deficit. Passive avoidance retention was similarly affected in the two aged subpopulations. Chronic oral administration of phosphatidylserine (50 mg/kg/day for up to 12 weeks), a pharmacologically active phospholipid, was found to improve both the spatial memory and the passive avoidance retention of aged impaired rats. Results are discussed with reference to the phosphatidylserine-induced improvement of age-associated deterioration of brain functions in rats.
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  • 149
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    Psychopharmacology 99 (1989), S. 299-303 
    ISSN: 1432-2072
    Keywords: Enkephalin analogues ; Intranigral infusions ; Dyskinetic biting ; Tardive dyskinesia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Leu- and Metenkephalin (Lenk and Menk) and their more stable analogues d-Ala-Leu- and d-Ala-Meten-kephalin (DALenk and DAMenk) as well as d-ala-d-Leu-and d-Ala-d-Metenkephalin (DADLenk and DADMenk) were infused bilaterally into substantia nigra in awake rats and oral movements were recorded for 90 min. DADLenk and DADMenk elicited dose-dependent biting dyskinesias with a chewing rate of about 90 jaw movements/min. DALenk produced a similar but weaker effect, whereas DAMenk, Lenk and Menk were ineffective in the doses given. These findings suggest a possible enkephalinergic mechanism underlying neuroleptic-induced tardive dyskinesias.
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  • 150
    ISSN: 1432-2013
    Keywords: Phosphaturia ; Parathyroid hormone ; 25 Hydroxy-vitamin D3 ; Trifluoperazine ; Adenylate cyclase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous work from this laboratory has demonstrated that 25(OH) vitamin D3 [25(OH)D3] acutely suppresses the phosphaturic action of parathyroid hormone (PTH) and interferes with the PTH-induced activation of adenylate cyclase (AC). Calmodulin inhibitors block vitamin D-induced Ca2+ transport in the gut and phosphorus uptake in renal BBMV's. We have examined whether calmodulin antagonists affect the renal action of 25(OH)D3. Acute clearance experiments were performed in PTH-infused parathyroidectomized rats receiving 25(OH)D3 after pretreatment with trifluoperazine (TFP) or promethazine (P). In vitro PTH-induced activation of renal AC was also studied in membrane preparations from pretreated rats in the presence of 25(OH)D3. 25(OH)D3 reduced the PTH-stimulated increase in fractional excretion of phosphorus (CP/CIn) from 0.292±0.024 to 0.195±0.018 (p〈0.005) and urinary cAMP from 149.3±20.3 to 78.1±10.4 pmol/min (p〈0.01) and also blunted AC activation in vitro. TFP but not P abolished the effects of 25(OH)D3 both in vivo and in vitro. R 24571 also abolished the in vitro effect of 25(OH)D3. Thus, (1) TFP abolishes both the antiphosphaturic and the AC/cAMP-related actions of 25(OH)D3, (2) P does not have these effects, and (3) R 24571 abolishes the in vitro effect of 25(OH)D3. These results suggest that the antiphosphaturic effect of 25(OH)D3 acting via the AC/cAMP system may be calmodulin dependent.
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  • 151
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    Archives of toxicology 63 (1989), S. 43-46 
    ISSN: 1432-0738
    Keywords: Styrene ; Testes ; Rat ; Enzymes ; Toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Styrene was administered through gavage to adult male rats for 60 days. At the lower dose of 200 mg/ kg/day no overt signs of testicular toxicity were observed, while at the higher dose of 400 mg/kg/day activities of some marker enzymes for testicular function were found to be altered significantly, along with a decrease in spermatozoa number. Histopathological studies revealed marked degeneration of seminiferous tubules and lumen devoid of sperms, further confirming testicular toxicity of styrene. The present study suggests an overall sensitivity of the male reproductive system towards styrene exposure.
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  • 152
    ISSN: 1432-0738
    Keywords: Methylmercury ; Protein synthesis ; Dorsal root ganglion ; Two-dimensional electrophoresis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dorsal root ganglia from control and methylmercury(MeHg)-treated rats were incubated in vitro with 35S-methionine ant the proteins synthesized were analyzed by two-dimensional electrophoresis. The double labelling method, in which proteins of control dorsal root ganglia labelled in vitro with 3H-leucine were added to each of the two samples as an internal standard, was used to minimize unavoidable errors arising from the resolving procedure itself. The results obtained showed that the effect of MeHg on the synthesis of proteins in dorsal root ganglia was not uniform for individual protein species in the latent period of MeHg intoxication. Among 200 protein species investigated, 157 showed inhibition of synthesis close to that of the total proteins in the tissue (68% of the control). Among the remaining protein species, 20 showed real stimulation of synthesis, whereas 7 were moderately inhibited and 16 were inhibited more strongly than the total proteins in the tissue. These results suggest that the effect of MeHg on the synthetic rates for protein species in dorsal root ganglia differs with the species, and that unusual elevation or reduction of the synthesis of some protein species caused by MeHg may lead to impairment of normal nerve functions.
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  • 153
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    Archives of toxicology 63 (1989), S. 320-324 
    ISSN: 1432-0738
    Keywords: Cadmium ; Rat ; Mechanical strength of bones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mechanical properties of the bones of young, adult and old rats administered various concentrations of cadmium were measured to prove the direct effect of cadmium on the bones of young rats. The young rats were divided into three subgroups, which were administered 0 (control), 5 and 10 ppm cadmium, respectively. The adult rats were subdivided into six groups, administered 0, 10, 20, 40, 80 and 160 ppm cadmium, respectively. The old rats were divided into three subgroups, which were administered 0, 80, and 160 ppm cadmium, respectively. The length of the administration was 4 weeks in every group. The decrease in the mechanical strengths of bones of young rats administered with cadmium was observed. On the other hand, no change in mechanical strength of bones was observed in the case of adult and old rats, administered up to 160 ppm cadmium. The correlation between the cadmium in bones and the decrease in the strength of the bone shows that cadmium directly affects the mechanical properties of bones of young rats.
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  • 154
    ISSN: 1432-0738
    Keywords: Cadmium ; Zinc ; Neonate ; Thymus ; Birth weight ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of cadmium exposure during pregnancy (by means of daily subcutaneous injections of 4.4 μmol/kg to the mother) on the neonates were investigated. No effect was observed on fetal or neonatal body weights, nor on neonatal liver weights. These parameters were examined up to 5 weeks after birth. The weight of neonatal thymuses was decreased 7 and 14 days after birth due to cadmium exposure of the mothers as compared with controls. This may be caused by zinc deficiency, because zinc concentrations in fetal and neonatal livers after cadmium exposure were found to be very low 20 days after conception and 5 h after birth. Cadmium concentration in neonatal liver decreased; however, cadmium in malignant liver increased as age increased. In the mother, cadmium was transferred to the milk, as it was demonstrated in the stomach contents of the pups. Simultaneous administration of zinc in amounts equimolar to cadmium did not have any noticeable effect on the amount of cadmium transferred to the fetus or on cadmium concentrations in any of the organs investigated. It could not prevent zinc deficiency in fetal and neonatal liver. In addition, growth retardation of the thymus from exposed pups could not be prevented by zinc administration.
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  • 155
    ISSN: 1432-0738
    Keywords: 2,4-Dichlorophenoxyacetic acid ; Biogenic amines ; Brain ; Cerebrospinal fluid ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Effects of single subcutaneous doses of sodium 2,4-dichlorophenoxyacetate (2,4-D-Na) on biogenic amines and their acidic metabolites in rat brain and cerebrospinal fluid (CSF) were analyzed by high pressure liquid chromatography. After 200 mg/kg 2,4-D-Na, the cerebral concentration of 5-hydroxytryptamine (5-HT) was increased slightly and that of 5-hydroxyindoleacetic acid (5-HIAA) roughly 3-fold between 1 and 8 h after the administration. There was also a tendency towards slightly lowered dopamine (DA) levels. No statistically significant changes in brain concentrations of noradrenaline (NA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) or tryptophan (TRY) were found. At the same time, however, the maximal increase in DOPAC, HVA and 5-HIAA concentrations in the CSF was 2.3–5.8-fold. The dependency of biogenic amines and metabolites on 2,4-D-Na dose was studied by injecting s.c. 0, 10, 30 and 100 mg/kg and sacrificing the rats at 2 h. In the brain, there was a dose-dependent increase in concentrations of 5-HIAA (at the two highest doses) and HVA (at the highest dose) while in the CSF those of all three acidic metabolites increased at the two highest doses. The 10 mg/kg dose had no effect. The results agree with the hypothesis that 2,4-D inhibits the organic acid transport out of the brain, which should then result in increased cerebral levels of acidic metabolites of biogenic amines, but it may also have effects on the activity of serotoninergic and dopaminergic neurones.
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  • 156
    ISSN: 1432-0738
    Keywords: Tellurium ; Rat ; Toxicology ; Immunomodulator ; Drug
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male and female Sprague Dawley rats were injected intraperitoneally for 4 weeks with ammonium trichloro (dioxyethylene-0-0′-) tellurate, an immunomodulating drug at closes ranging from 3 to 24 mg/kg/week. Routine laboratory examinations included body weight, food consumption, clinical chemistry and hematological examinations. At termination of the experiment, all rats were sacrificed and subjected to a detailed necropsy. Few mortalities were recorded during the course of the study. Clinical signs included hind limb paresis and paraphimosis. A garlic odor pervaded the room. Body weight and food consumption were adversely affected in a dose-related manner. Effects were elicited on the hematological system; changes being noted in the platelet and leukocyte counts as well. Clinical chemistry evaluation revealed signs of hepatoxicity, especially in the female treated groups. The level of beta-globulin was increased. At necropsy organs were found to have a grayish-blue discoloration. Tellurium related histopathological changes were observed in the eyes, liver, thymus, bone marrow, heart and kidneys. An attempt has been made to compare the toxicity of this drug with other tellurium-containing compounds. A good correlation was found. Novel effects of the drug were retinopathy and replacement of bone marrow by bony or fibrous tissue. The possibility that some of the effects may have been elicited due to selenium-vitamin E deficiency has been considered.
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  • 157
    ISSN: 1432-1351
    Keywords: Rat ; Melatonin ; Circadian rhythm ; 5-hydroxytryptophan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The rhythm in melatonin production in the rat is driven by a circadian rhythm in the pineal N-acetyltransferase (NAT) activity. Rats adapted to an artificial lighting regime of 12 h of light and 12 h of darkness per day were exposed to an 8-h advance of the light-dark regime accomplished by the shortening of one dark period; the effect of melatonin, triazolam and fluoxetine, together with 5-hydroxytryptophan, on the reentrainment of the NAT rhythm was studied. In control rats, the NAT rhythm was abolished during the first 3 cycles following the advance shift. It reappeared during the 4th cycle; however, the phase relationship between the evening rise in activity and the morning decline was still compressed. Melatonin accelerated the NAT rhythm reentrainment. In rats treated chronically with melatonin at the new dark onset, the rhythm had already reappeared during the 3rd cycle, in the middle of the advanced night, and during the 4th cycle, the phase relationship between the evening onset and the morning decline of the NAT activity was the same as before the advance shift. In rats treated chronically with melatonin at the old dark onset or in those treated with melatonin 8 h, 5 h and 2 h after the new dark onset during the 1st, 2nd and 3rd cycle, respectively, following the advance shift, the NAT rhythm reappeared during the 3rd cycle as well but in the last third of the advanced night only. Neither triazolam nor fluoxetine together with 5-hydroxytryptophan administered around the new dark onset facilitated NAT rhythm reentrainment after the 8-h advance of the light-dark cycle.
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  • 158
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    Journal of cancer research and clinical oncology 115 (1989), S. 47-52 
    ISSN: 1432-1335
    Keywords: Alkylation ; Alkyl guanines ; Pancreas DNA ; Nitrosamines ; Acinar cells ; Duct cells ; Hamster ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activation of 3H-labeled N-nitrosobis(2-oxopropyl)amine ([3H]BOP) by pancreas acinar and duct tissue from Syrian hamsters and MRC-Wistar rats in vitro was measured as DNA alkylation. Hamster tissue was incubated with [3H]BOP (0.1 mM; 20 μCi/ml) for 2 h. Initial levels of alkylation were similar, 41.7±3.7 (acinar) and 51.5±7.8 (duct) dpm/μg DNA. Alkylation persisted for longer in duct (t/2〉46 h) than in acinar tissue (t/2=6 h). The faster repair of alkylation in acinar tissue was not due to acinar cell death. In rat duct tissue the level of alkylation 2 h after incubation (38.9±4.5 dpm/μg DNA) was similar to that in hamster ducts but declined more rapidly (t/2=27 h). Hamster and rat acinar and duct tissue was incubated with BOP followed by [3H]thymidine to measure DNA synthesis. BOP stimulated DNA synthesis in hamster but not in rat duct tissue or hamster acinar tissue. These data support the hypothesis that the duct tissue is the target tissue for BOP in Syrian hamsters.
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  • 159
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    Psychopharmacology 99 (1989), S. 473-478 
    ISSN: 1432-2072
    Keywords: Nicotine ; Self-administration ; Reinforcement ; Mecamylamine ; Hexamethonium ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intravenous nicotine maintained substantial responding on the drug-reinforced lever with a limited-access, fixed-ratio 5 schedule of self-administration. Responding demonstrated the expected pharmacological sensitivity; it was dose-dependently reduced by pre-session treatment with either nicotine or mecamylamine but not with hexamethonium. In addition, responding was dependent on the size of the unit dose, with maximum values occurring at 0.01 and 0.03 mg/kg/infusion. Self-administration behavior decreased at doses both above and below these, and extinction followed the substitution of saline for nicotine. Total session drug intake increased with unit dose up to a maximal value of approximately 0.5 mg/kg at 0.03 mg/kg/infusion, but did not increase further at the 0.06 mg/kg/infusion dose. A decrease in the time-out duration at the dose of 0.03 mg/kg/infusion also did not change the total session intake of nicotine. It is suggested that nicotine intake is controlled both by the total amount of drug obtained and by the magnitude of the unit dose. These results demonstrate that intravenous nicotine can maintain substantial self-administration behavior in rodents.
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  • 160
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    Psychopharmacology 99 (1989), S. 558-562 
    ISSN: 1432-2072
    Keywords: Nucleus accumbens ; Dopaminergic mechanisms ; Selective drugs ; Microinjections ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of intra-accumbens injections of various dopaminergic agonists and antagonists on the rat locomotor activity has been evaluated in automated open fields. Locomotor stimulation has been observed after local administration ofd-amphetamine (10 μg), apomorphine (10 μg), as well as of solution containing the D1 agonist SKF 38 393 and D2 receptor agonist LY 171 555 (quinpirole) in doses (10 and 4 μg, respectively) which were inactive when both drugs were administered separately. On the other hand separate injections of metoclopramide (0.1 μg) and SCH 23 390 (0.5 μg) (D2 and D1 receptor antagonists) very potently inhibited animals' locomotor activity. The data indicate that concomitant stimulation of both accumbens D1- and D2-receptor related mechanisms is a necessary condition to increase rat motility. Moreover, it seems that accumbens D1 receptors may be differently involved in the control of facilitatory versus inhibitory motor processes.
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  • 161
    ISSN: 1432-2072
    Keywords: Feeding ; 5-HT antagonists ; 5-HT1 receptors ; 5-HT1C receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of nine central 5-HT antagonists on food intake in free feeding male rats were examined. The 5-HT2 antagonists ritanserin and ketanserin and the selective 5-HT3 antagonists ICS 205-930 and MDL 72222 had no effect on food intake. In contrast, the non-selective 5-HT antagonists metergoline, methiothepin, mesulergine, mianserin and methysergide (all of which have high affinity for various 5-HT1 receptor subtypes), dose-dependently increased food intake during a 4-h daytime test. Furthermore, metergoline dose dependently increased food intake over a 24-h period. Suprisingly, mesulergine decreased food intake over a 24-h period at the same doses that increased daytime food intake. This may indicate that the increase in daytime feeding produced by mesulergine is a non-specific response. Although the antagonists used have varying degrees of selectivity for 5-HT receptor subtypes, the pattern of results suggests that postsynaptic 5-HT1 receptors (possibly of the 5-HT1C type) play an important role in the control of feeding in rats.
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  • 162
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    Psychopharmacology 98 (1989), S. 286-288 
    ISSN: 1432-2072
    Keywords: IP pirenzepine ; Passive avoidance ; Brain penetration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract When injected IP, the M1 muscarinic receptor antagonist pirenzepine dose-dependently induced a deficit in passive avoidance learning in rats. This activity was optimal at 75 mg/kg injected 1 h before the acquisition session. The deficit induced by pirenzepine was antagonized by oxotremorine (0.03–0.3 mg/kg SC) and physostigmine (0.1 mg/kg SC), but not neostigmine. By comparison, under the same experimental conditions, physostigmine and oxotremorine also antagonized the deficit induced by an equipotent dose of scopolamine (0.5 mg/kg IP), although the activity of physostigmine appeared stronger against scopolamine than against pirenzepine. These results suggest that pirenzepine could produce a centrally-mediated behavioural disruption when injected systemically.
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  • 163
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    Psychopharmacology 98 (1989), S. 412-416 
    ISSN: 1432-2072
    Keywords: Adrenoceptors ; Behaviour ; Noradrenaline ; Open field ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were injected IP once daily for 14 consecutive days with propranolol (5 mg/kg), yohimbine (2.5 mg/kg) or saline vehicle. A fourth group was unhandled during this time. Each rat was then placed in an open field for 4 min and its activity and defaecation recorded. Immediately after this, the animals were killed and cerebral cortices removed for radioligand binding to α2- and β-adrenoceptors and measurement of noradrenaline content. We report two sets of findings. First, β-adrenoceptor density correlated positively, and affinity negatively, with the number of movements towards the centre of the field in the final 3 min of the trial. α2-Adrenoceptor K d, in contrast, correlated both with movements around the field and those directed towards the centre. Secondly, whereas the only specific drug effect was an increase in defaecation after treatment with propranolol, β-adrenoceptor density was increased and affinity decreased in all injected groups, suggesting a non-specific effect of the stress of injection. Movements to and from the centre of the field were also increased in injected groups during the first minute of the trial. In both sets of findings the association of β-adrenoceptor density with greater resistance to stress is hard to reconcile with existing theories of the role of β-adrenoceptors in behavioural responses to stress.
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  • 164
    ISSN: 1432-2072
    Keywords: Penile erection ; Yawning ; Hypophysectomy ; Monosodium glutamate ; Oxytocin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Penile erection and yawning induced by the intracerebroventricular (ICV) injection of oxytocin (10–1000 ng) was studied in hypophysectomized rats and in rats neonatally treated with monosodium glutamate (MSG), a treatment that depletes hypothalamic opiomelanocorticotropinderived peptides without altering their pituitary and circulating concentration. Oxytocin effect was strongly reduced by hypophysectomy, but not by neonatal MSG. Testosterone replacement (50 μ/kg/day for 23 days) partially reversed the effect of hypophysectomy on penile erection, but not on yawning. The present results suggest that oxytocin does not induce penile erection and yawning by releasing an ACTH-derived peptide from hypothalamic opiomelanotropinergic neurons, and that the pituitary gland exerts a permissive role on the expression of the above behavioural responses induced by oxytocin.
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  • 165
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    Naunyn-Schmiedeberg's archives of pharmacology 340 (1989), S. 541-546 
    ISSN: 1432-1912
    Keywords: Ruthenium Red ; Capsaicin ; Sensory nerves ; Rat ; Urinary bladder
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary (1) Topical administration of Ruthenium Red (10–100 μM in saline) to the serosal surface of the urinary bladder in urethane-anesthetized rats prevented the motor response of the urinary bladder to topical administration of capsaicin and protected the sensory fibers from capsaicin desensitization, but had no effect on the volume-evoked contractions (micturition reflex). At 1 mM increased bladder capacity and decreased amplitude of micturition contraction were observed. (2) At 100 μM, topical Ruthenium Red prevented the blood pressure rise produced by topical administration of capsaicin onto the bladder but did not affect the blood pressure rise produced by sudden bladder distension in spinal rats. (3) After intrathecal administration, Ruthenium Red (80–800 ng/rat) produced a long lasting inhibition of the micturition reflex in urethane-anesthetized rats, this effect being evident in both vehicleor capsaicin- (50 mg/kg s. c. 4 days before) pretreated rats. At 800 ng/rat, intrathecal Ruthenium Red did not affect the blood pressure rise produced by topical administration of capsaicin onto the rat bladder nor that produced by bladder distension. (4) These findings provide further evidence that Ruthenium Red acts quite selectively as a “capsaicin antagonist” preventing both reflex and “efferent” responses activated by peripherally administered capsaicin. By contrast, sensory impulse generation by a natural stimulus such as bladder distension is apparently unaffected by Ruthenium Red. The marked inhibition of the micturition reflex observed after intrathecal administration of Ruthenium Red does probably not involve an interaction with primary afferents in the spinal cord.
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  • 166
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    Naunyn-Schmiedeberg's archives of pharmacology 339 (1989), S. 312-314 
    ISSN: 1432-1912
    Keywords: Locus coeruleus ; Rat ; Excitatory amino acids ; Kynurenic acid ; Mg2+
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The goal of this study was to investigate whether locus coeruleus neurons of the rat are sensitive to agonists of the different excitatory amino acid receptors. All experiments were performed on a midpontine rat slice preparation. Bath-applied l-glutamate, kainate, N-methyl-d-aspartate (NMDA) and quisqualate induced concentration-dependent activations of all neurons which were reflected in an increase of the neurons' mean discharge rate. The rank order of cell activation was kainate ∼ quisqualate 〉 NMDA 〉 l-glutamate. None of the agonists induced a bursting-type of discharge. The NMDA-receptor blocker dl-2-amino-5-phosphonovaleric acid (APV, 30 μM) selectively antagonized the NMDA-induced increase in cell firing. Kynurenic acid (100 μM) non-selectively attenuated the response to NMDA, kainate and quisqualate. Neither APV nor kynurenic acid per se had any effect on the spontaneous firing rate. If the Mg2+ concentration in the superfusion medium was lowered from 2 mM to nominally zero the response to NMDA was selectively increased. In conclusion, locus coeruleus neurons share with other neurons their sensitivity to agonists of all three types of excitatory amino acid receptors. However, in contrast to other neurons, they do not respond with a bursting type of discharge.
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  • 167
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    Naunyn-Schmiedeberg's archives of pharmacology 339 (1989), S. 551-556 
    ISSN: 1432-1912
    Keywords: Dopamine ; 5-HT synthesis ; Brain ; 8-OHDPAT ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Regional dopamine synthesis in the rat striatum was estimated by measuring DOPA accumulation following inhibition of cerebral aromatic l-amino acid decarboxylase by means of NSD-1015, 100 mg kg−1 intraperitoneally. In animals treated with reserpine, 5 mg kg−1 subcutaneously −18 h, there was a statistically significant increase in DOPA accumulation in the nucleus accumbens, the ventro-medial neostriatum, the dorso-lateral neostriatum and in the posterior limb of the neostriatum. This increase in DOPA accumulation was antagonized dose-dependently in the nucleus accumbens and ventro-medial neostriatum, but not in the other two regions, by treatment with the 5-HT1A receptor agonist 8-OH-DPAT, 0.15–2.4 μmol kg−1, whereas the partial dopamine D2 receptor agonist (−)3-PPP, 2.5–10.0 μmol kg−1, or the full dopamine D2 receptor agonist quinpirole, 0.05–0.8 μmol kg−, antagonized the reserpine-induced increase in DOPA accumulation uniformly in all four regions of the striatum. The suppression of DOPA accumulation by 8-OH-DPAT in reserpine-treated animals, was completely antagonized by raclopride, 1 μmol kg−1, but not by (−)pindolol, 8 μmol kg−1. The accumulation of 5-HTP in all regions of the striatum as well as in the neocortex following decarboxylase inhibition and reserpine pretreatment, was also inhibited by 8-OH-DPAT, and this inhibition was unaffected by treatment with raclopride or (−)pindolol. It is concluded that 8-OH-DPAT, in addition to general effects on forebrain 5-hydroxytryptamine synthesis, selectively affects limbic forebrain dopamine synthesis. This latter effect is probably due to direct stimulation of dopamine autoreceptors, since it was obtained in reserpine-treated rats, and was completely antagonized by raclopride, but not (−)pindolol.
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  • 168
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    Naunyn-Schmiedeberg's archives of pharmacology 340 (1989), S. 161-169 
    ISSN: 1432-1912
    Keywords: Amperozide ; Rat ; Behavioural stimulation ; Monoamines ; Biochemical effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Amperozide (FG 5606; N-ethyl-4-[4′,4′-bis(p-fluorophenyl) butyl]-1-piperazinecarboximide) is a new putatively antipsychotic compound with a postulated 5-HT2 antagonistic profile. Somewhat surprisingly amperozide dose dependently induced a behavioural stimulation in reserpinized and in nonpretreated rats. The behaviour consisted of both forward and backward locomotion as well as forepaw circling and a grooming like behaviour. Since the behavioural pattern clearly differ from that produced by classical dopaminergic or serotonergic agonists (e. g. apomorphine or 8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT), and has not been previously reported, we decided to investigate the origin of this effect. In the behavioural paradigms it was not possible to antagonize the amperozide stimulation in reserpinized rats with the dopamine receptor blockers haloperidol, raclopride or R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine, SCH 23390. Neither the 5-HT2 receptor blocking agent ritanserin nor the tryptophan and tyrosine hydroxylase inhibitor DL-3,4-dihydroxy-phenyl-α-propylacetamide, H22/54, could block the motoric stimulation or the forepaw circling behaviour produced by amperozide. However, the noradrenaline synthesis inhibitor bis- (4-methyl-1-homopiperazinylthiocarbonyl)-disulfide, FLA 63, as well as the α-adrenoceptor antagonist phenoxy-benzamine, could partly inhibit the locomotor stimulation. Hence, noradrenaline seems to be, at least in part, involved in the behavioural stimulatory effect of amperozide. synthesis rate (DOPA formation) in normal or reserpinized animals in the striatal or the limbic brain regions. In reserpinized animals amperozide also failed to antagonize the decrease in DOPA formation after apomorphine and 3-hydroxy-benzylhydrazine HCl, NSD 1015, in these regions. Thus, amperozide failed to show agonistic or antagonistic action on central dopamine receptors. However, in the noradrenaline rich cortical region amperozide induced an increase in DOPA accumulation. The compound also increased the levels of normetanephrine as well as antagonized the decrease in DOPA accumulation by clonidine in the cortical brain region. Amperozide also increased the disappearence rate of noradrenaline after inhibitor of tyrosine hydroxylase by α-methyl-para-tyrosine. These data suggest that, biochemically, amperozide has got α2 antagonistic properties. However, it is not evident that these biochemical properties are responsible for the behavioural effects of amperozide.
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  • 169
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    Cell & tissue research 256 (1989), S. 553-558 
    ISSN: 1432-0878
    Keywords: Transforming growth factor (TGF)-β ; Myocardium ; mRNA ; Fibroblast ; Cardiomyocyte ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Transforming growth factor-β (TGF-β) is a biologically active polypeptide present in normal tissues as well as transformed cells. Two structurally related forms of this peptide are TGF-β 1 and TGF-β 2. Using freshly isolated cardiomyocytes and non-myocyte heart cells, and a [32P]-labelled cDNA probe to human TGF-β 1, we demonstrated that mRNA for TGF-β 1 could be detected only in the nonmyocyte fraction of heart cells. In the present study, the distribution of TGF-β 1 in the heart was determined by immunofluorescence staining by use of a polyclonal antibody to porcine TGF-β 1 in cryostat sections of rat heart. Immunofluorescence staining was intense around the blood vessels and radially diffuse in the surrounding myocardium.
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  • 170
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    Cell & tissue research 256 (1989), S. 303-307 
    ISSN: 1432-0878
    Keywords: Arachnoid cells ; Tight and gap junctions ; Cold injury ; Ultrastructure ; Freeze-fracture technique ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The junctional complexes of cells in the outer arachnoid layer overlying the cerebral cortex of 2-week-old rats were examined with freeze-fracture electron microscopy up to 60 min after transcranial cold injury to the dorsal surface of the brain. Within 30 min after injury, areas of gap and tight junctions with morphological features characteristic of junction formation and/or junction disruption were found scattered among normal junctional complexes in some arachnoid cells. Within 60 min after injury, tight junctions with features typical of less leaky zonulae occludentes were present in all arachnoid cells examined. These morphological features include increases in the number of tight junctional strands and the number of strand-to-strand anatomoses. Gap junctions were interspersed among the tight junctional strands, and many were completely encircled by the strands. The increase in the number and complexity of the tight junctional strands in response to brain injury may be the morphological basis for the maintenance of the cerebrospinal fluid-blood dural barrier.
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  • 171
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    Cell & tissue research 256 (1989), S. 559-565 
    ISSN: 1432-0878
    Keywords: Retrograde tracing ; Immunocytochemistry ; Vascular innervation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The origin of nerve fibers to the superficial temporal artery of the rat was studied by retrograde tracing with the fluorescent dye True Blue (TB). Application of TB to the rat superficial temporal artery labeled perikarya in the superior cervical ganglion, the otic ganglion, the sphenopalatine ganglion, the jugular-nodose ganglionic complex, and the trigeminal ganglion. The labeled perikarya were located in ipsilateral ganglia; a few neuronal somata were, in addition, seen in contralateral ganglia. Judging from the number of labeled nerve cell bodies the majority of fibers contributing to the perivascular innervation originate from the superior cervical, sphenopalatine and trigeminal ganglia. A moderate labeling was seen in the otic ganglion, whereas only few perikarya were labeled in the jugular-nodose ganglionic complex. Furthermore, TB-labeled perikarya were examined for the presence of neuropeptides. In the superior cervical ganglion, all TB-labeled nerve cell bodies contained neuropeptide Y. In the sphenopalatine and otic ganglia, the majority of the labeled perikarya were endowed with vasoactive intestinal polypeptide. In the trigeminal ganglion, the majority of the TB-labeled nerve cell bodies displayed calcitonin gene-related peptide, while a small population of the TB-labeled neuronal elements contained, in addition, substance P. In conclusion, these findings indicate that the majority of peptide-containing nerve fibers to the superficial temporal artery originate in ipsilateral cranial ganglia; a few fibers, however, may originate in contralateral ganglia.
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  • 172
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    Cell & tissue research 256 (1989), S. 447-456 
    ISSN: 1432-0878
    Keywords: MAP2 ; Actin ; Dendritic spines ; Spine apparatus ; Spine synapses ; Postsynaptic density ; Synaptic plasticity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The distribution of MAP2 and actin in dendritic spines of the visual and cerebellar cortices, dentate fascia, and hippocampus was determined by using immunogold electron microscopy. By this approach, we have confirmed the presence of MAP2 in dendritic spines and identified substructures within the spine compartment showing MAP2 immunoreactivity. MAP2 immunolabeling was mainly associated with filaments which reacted with a monoclonal anti-actin antibody. Also, by immunogold double-labeling we colocalized MAP2 with actin on the endomembranes of the spine apparatus, smooth endoplasmic reticulum, and in the postsynaptic density. Labeling was nearly absent in axons and axonal terminals. These results indicate that MAP2 is an actin-associated protein in dendritic spines. Thus, MAP2 may organize actin filaments in the spine and endow the actin network of the spine with dynamic properties that are necessary for synaptic plasticity.
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  • 173
    ISSN: 1432-0878
    Keywords: Adrenal medullary endothelial cells ; Pheochromocytoma (PC12) cells ; Co-culture ; Cell surface extracts ; Adhesion ; Cell-cell interactions ; Bovine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Chromaffin cells in the adrenal medulla are found in close proximity to capillary endothelial cells, thereby forming the classical endocrine complex. To examine the possible chemical basis of their interaction in more detail, we have grown bovine adrenal medullary endothelial (BAME) cells in monolayer cultures and added to them pheochromocytoma (PC12) cells, a chromaffin tumor cell line of rats. The PC12 cells were chosen because of the similarities they share with adrenal medullary chromaffin cells. PC12 cells rapidly attached to BAME cells cultures, their rate of adhesion being significantly enhanced over binding of PC12 cells to either uncoated plates or to monolayers of unrelated cell cultures. Consistent with this observation, we noted that the extracellular matrix (ECM) derived from the BAME cells did not enhance PC12 cell adhesion and did not promote neurite sprouting as previously described for ECM derived from corneal endothelial cells. The specific adhesion between PC12 and BAME cells could be abolished by cell surface extracts derived from these two cells but not by extracts derived from unrelated cell types. This activity was heat-labile, sensitive to trypsin and, to a lesser extent, to neuraminidase. We therefore conclude that PC12 cells may interact with BAME cells by specific proteinaceous adhesive factors associated with their plasma membranes. These interactions might represent the formative role of cell-cell contacts in the organization of the developing adrenal gland.
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  • 174
    ISSN: 1432-0878
    Keywords: SEM ; TEM ; Interstitial cell ; Myenteric plexus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary An extensive cellular network becomes visible over the myenteric plexus of the rat after removal of the overlying tissues under the scanning electron microscope. The cells are mainly stellate and have many slender processes via which they interconnect. They form a three-dimensional network and are closely associated with the ganglia and nerve bundles, and also extend over the smooth muscle cells. They are considered to correspond to the interstitial cells of Cajal because of their peculiar arrangement and their topography. Transmission electron-microscopic evidence demonstrates that the majority of those cells have features of fibroblasts. Gap junctions and intermediate junctions are observed between these fibroblast-like cells, and also between them and smooth muscle cells. Examination of serial thin sections reveals that single fibroblast-like interstitial cells connect to both circular and longitudinal muscle cells via gap junctions. It is suggested that the network of interstitial cells conducts electrical signals.
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  • 175
    ISSN: 1432-0878
    Keywords: Gastrin ; Gastrin-releasing peptide ; Bombesin ; Stomach ; Autonomic innervation ; Immunohistochemistry ; Guinea pig ; Rat ; Dog ; Man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The relationship between bombesin-like immunoreactive (bombesin-LI) nerve fibres and gastrin-LI G-cells was examined in gastric antral mucosa from guineapig, rat, dog and man using a double-labelling fluorescence immunohistochemical technique. The greatest density of bombesin-LI nerve fibres was found within the basal mucosa in all species and the density of innervation decreased towards the luminal surface. Most G-cells were in a band occupying approximately the middle third of the mucosa. The proportion of G-cells found within a distance of 2 μm from bombesin-LI nerve fibres was low in all species (6% in the guinea-pig, 22% in the rat, 14% in the dog, and 9% in the human). It is proposed that the neuropeptide released from bombesin-LI antral mucosal nerve fibres traverses distances of greater than several μm to reach the target G-cells. This may be achieved by passage through the mucosal microcirculation.
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  • 176
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    Cell & tissue research 257 (1989), S. 263-268 
    ISSN: 1432-0878
    Keywords: Retinol ; Vacuoles ; Immunohistochemistry ; Plasma proteins ; Hepatocytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The vacuoles occurring in rat hepatocytes after intraportal injection of retinol (33 or 67 μg) were examined immunohistochemically using respective antibodies against rat albumin, human retinol-binding protein, human ceruloplasmin, human α 1-antitrypsin, human transferrin, and human prealbumin as representative plasma proteins. The occurrence of the vacuoles reached a numerical maximum 30 min after injection of 67 μg retinol, followed by a temporal decrease. Hepatocytes from control rats, which had been intraportally injected with either blood plasma diluted to 2/3 concentration or with retinol palmitate solvent (castor oil) dissolved in blood plasma, showed immunoreactive fine granules without the occurrence of vacuoles in the cytoplasm. Identical vacuoles in serial sections appeared immunohistochemically either immunoreactive or non-immunoreactive for all the antibodies used, with rare exceptions. The occurrence of several rare exceptions suggested that 2 kinds of vacuoles might be formed in different cytoplasmic compartments. A zonal distribution of vacuoles was apparent in the hepatic laminae (or acini) within the liver lobules. The vacuoles were predominantly distributed in zone 2, and to a lesser extent in zone 3 and zone 1 in that order.
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    European journal of applied physiology 58 (1989), S. 446-451 
    ISSN: 1439-6327
    Keywords: Rectal temperature ; Tail vasomotor response ; Exercise ; Estrus cycle ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In female rats, rectal temperature (T re), tail vasomotor response, oxygen uptake $$\left( {\dot V_{{\text{O}}_{\text{2}} } } \right)$$ , and carbon dioxide production $$\left( {\dot V_{{\text{CO}}_{\text{2}} } } \right)$$ were measured in proestrus and estrus stages during treadmill running at two different speeds at an ambient temperature (T a) of 24° C. Experiments were performed at 2.00–6.00 a.m., when the difference inT re was greatest between the two stages;T re at rest in the estrus stage was 0.54° C higher than in the proestrus stage. In a mild warm environment, thresholdT re for a rise in tail skin temperature (T tail) was also higher in the estrus stage than in the proestrus stage. In contrast, no difference was seen in the thresholdT re and steady stateT re at the end of exercise between proestrus and estrus stages. These values were higher at the higher work intensity. $$\dot V_{{\text{O}}_{\text{2}} } $$ was also similar between the two stages, except in the second 5 min after the beginning of exercise, when $$\dot V_{{\text{O}}_{\text{2}} } $$ was greater andT re rose more steeply in the proestrus stage. These data indicate that deep body temperature during exercise is regulated at a certain level depending on the work intensity and is not influenced by the estrus cycle.
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  • 178
    ISSN: 1435-2451
    Keywords: Portocaval shunt ; Liver cirrhosis ; Rat ; Lethality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Im Lebercirrhose-Modell der Ratte hat die portocavale Anastomose eine sehr hohe Letalitet (87%). Durch eine präoperative Vorbereitung mittels einer Therapie, die einen eta blierten Stellenwert in der Behandlung der portosy stemischen Encephalopathie hat, wird erstmals experimentell eine Senkung der Operationsletalität dokumentiert, was den konsequenten klinischen Einsatz nahelegt.
    Notes: Summarry Following portocaval anastomosis a high lethality (87%) can be observed in a standardized micronodular liver cirrhosis model. By a special preoperative regimen this lethality can be reduced to 10%.
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    Journal of comparative physiology 159 (1989), S. 237-242 
    ISSN: 1432-136X
    Keywords: Amylase ; Mosquitofish ; Rat ; Drosophila ; Structure ; Function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Amylases from the mosquitofish (Gambusia affinis holbrooki, Pisces: Poeciliidae) and rat were purified and compared withDrosophila amylases in terms of structure and function. At the structural level, amino acid compositions of the three amylases were compared. At the functional level, amylase activities were compared on various substrates and in the presence of inhibitors. While the amylases from all three organisms had properties typical of alpha-amylases, both structural and functional differences were observed. Using resemblance coefficients of distance and similarity from numerical taxonomy, it was determined that the amylases from the rat andDrosophila were more similar to each other than either was to amylase from the mosquitofish, and that structural differences between the amylases did not reflect functional differences, i.e. there was no correlation between amylase structural and functional distances.
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    Naunyn-Schmiedeberg's archives of pharmacology 337 (1988), S. 1-8 
    ISSN: 1432-1912
    Keywords: 5-Hydroxytryptamine ; 5-HT receptors ; 5-Carboxamidotryptamine ; Rat ; Cardiovascular
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Peripheral 5-HT receptor-mediated responses were examined in pithed spontaneously hypertensive rats and normotensive wistar rats. Responses examined were: Pressor and depressor responses, tachycardia and inhibition of stimulation-evoked tachycardia. In pithed spontaneously hypertensive rats, 5-HT, but not the 5-HT1-selective agonist 5-carboxamidotryptamine, produced pressor responses, and these were potently antagonised by the 5-HT2-selective antagonists ketanserin and LY 53857. In pithed spontaneously hypertensive rats, the tachycardia to 5-HT was abolished by a combination of the 5-HT2 receptor antagonist LY 53857 and propranolol, suggesting that the tachycardia is mediated by 5-HT2 receptors and by release of noradrenaline. In pithed spontaneously hypertensive rats, 5-carboxamidotryptamine, 5-HT, and to a lesser extent the 5-HT1 receptor agonist RU 24969, but not the 5-HT1A receptor agonist 8-OH-DPAT, produced depressor responses which were antagonised by methysergide and metitepin, but which do not clearly fit with any of the 5-HT, ligand binding sites. In pithed normotensive wistar rat, 5-carboxamidotryptamine was approximately 100 times more potent than 5-HT and 8-OH-DPAT at inhibiting the cardio-acceleration produced by single pulse electrical stimulation and this inhibition was antagonised by metitepin, so that the response is mediated by 5-HT1 receptors.
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    Naunyn-Schmiedeberg's archives of pharmacology 337 (1988), S. 164-168 
    ISSN: 1432-1912
    Keywords: Central nervous system ; Alpha-2 adrenoceptors ; Oxymetazoline ; Vagus nerve ; Pituitary gland ; Vasopressin ; Gastric secretion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The mechanism of the gastric antisecretory action of the stimulation of central alpha-2 adrenoceptors were studied in conscious, pylorus-ligated rats using intracerebroventricularly (i.c.v.) administered oxymetazoline as the model substance. I.c.v. administration of 10 μg of oxymetazoline strongly inhibited the secretion of acid, pepsin and fluid, whereas upon s.c. injection this dose was without any effect. Pretreatment with idazoxan abolished the antisecretory effect of i.c.v. administered oxymetazoline. I.c.v. injected oxymetazoline inhibited gastric secretion induced by carbachol in vagotomized rats, but the inhibitory effect was less pronounced than on the spontaneous secretion in rats with intact vagi. Hypophysectomy abolished the antisecretory effect of i.c.v. oxymetazoline, and pretreatment with the vasopressin antagonist, d(CH2)5Tyr(Me)AVP, significantly attenuated it. The results suggest that the inhibition of gastric secretion by the stimulation of central alpha-2 adrenoceptors in rats is mediated in part by vasopressin released from the pituitary gland.
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  • 182
    ISSN: 1432-1912
    Keywords: Calcitonin gene-related peptides ; Tachykinins ; Capsaicin ; Cardiac sensory nerves ; Rat ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The effects of calcitonin gene-related peptide (CGRP), neurokinin A (NKA), neuropeptide K (NPK) and substance P (SP) on contractility of the guinea-pig and rat heart were studied in vitro in relation to the response to capsaicin. 2. Human (h) CGRP alpha (a) and beta (β) were equipotent in stimulating the contractile force and rate of the spontaneously beating guinea-pig right atrium. 3. Both NKA and NPK inhibited contractile force and rate in the guinea-pig atrium whilst a mainly negative chronotropic effect was observed in the whole heart. SP did not influence cardiac contractility. 4. Human CGRP α and β mimicked the contractile effects of capsaicin in the guinea-pig atrium. In the whole heart preparation, hCGRP α and capsaicin increased heart rate whereas capsaicin also evoked an atropine-resistant inhibition of contractile force. The stimulatory effect of capsaicin on heart rate was absent after systemic capsaicin pretreatment, while the inhibition of ventricular contractile tension remained unchanged. 5. Extended incubation with hCGRP α or β was associated with development of cross-tachyphylaxis between these two agents in the guinea-pig atrium. However, CGRP tachyphylaxis did not change the atrial response to noradrenaline, forskolin or NKA. The stimulatory effects of capsaicin on atrial contractility were absent after tachyphylaxis to hCGRP α or β. 6. There was no detectable supersensitivity to the stimulatory effects of rat (r) CGRP α on the spontaneously beating atrium after capsaicin pretreatment of adult or neonatal rats. In conclusion the present data provide further evidence that the capsaicin-induced stimulation of atrial contractility is due to local release of CGRP. CGRP tachyphylaxis seems to be a specific, receptor-mediated event and is not related to down-regulation of the adenylate cyclase system. The inhibition of the contractile force in whole heart preparations by capsaicin is most likely due to a non-cholinergic effect independent of tachykinin release.
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  • 183
    ISSN: 1432-0983
    Keywords: Ribosomal protein ; Immunological homology ; Yeast ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Polyclonal antibodies raised against ribosomal protein (r-protein) L2 of Schizosaccharomyces pombe were used to check for cross-reaktions with total r-proteins of rat liver. Using this procedure, the rat liver r-proteins, L4 and L24, were identified as being immunologically related to yeast L2. In addtional, homologies between rat liver L4 and L24 were detected. The possible implications for the regulation of r-protein synthesis are discussed.
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    Pediatric surgery international 3 (1988), S. 338-342 
    ISSN: 1437-9813
    Keywords: Spleen ; Autotransplantation ; Protective function ; Malaria ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Autologous splenic fragments regenerate after transplantation. The regenerated mass only attains a small proportion of that of the normal spleen. Some data on the protective function are controversial. Malaria parasites were inoculated to test splenic function in rats. Peak parasitemia, the course of parasitemia, and anemia were comparable in normal and autotransplanted rats. In rats with splenic transplants only the duration of the parasitemia was longer than in normal rats. In contrast, splenectomized rats were unable to clear the parasites from the blood and became progressively anemic. After stimulating regeneration by increasing the work load to the white pulp or the macrophage system, more regenerated tissue was found, but the protective function did not increase. The amount of regenerated splenic tissue does not correlate with its protective function.
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  • 185
    ISSN: 1432-2307
    Keywords: Mammary neoplasms ; DMBA ; Rat ; Carcinoma ; Sarcoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mammary tumours were induced by the direct dusting of 1 mg, 7,12-dimethylbenz(a)anthracene (DMBA) powder onto the mammary gland of both 30-day-old female and male Sprague-Dawley rats, and the tumours were examined histologically. Mammary tumours developed in 43/43 (100%) of the females 11 to 20 weeks after DMBA dusting and 16/23 (70%) of the males 18 to 28 weeks after dusting, while non-mammary spindle cell sarcomas occurred in 5/23 (22%) of the males 15 to 24 weeks after dusting. A variety of benign and malignant mammary tumours of epithelial and/or mesenchymal origin were induced, which are comparable to human mammary tumours. Different histological patterns were observed in different areas of the same tumours. Ovariectomy revealed hormone (ovary)-dependency in 10/17 (59%) of the tumours, revealing regressing epithelial and proliferating mesenchymal tumour elements on histological examination.
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  • 186
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    Virchows Archiv 414 (1988), S. 77-81 
    ISSN: 1432-2307
    Keywords: Epithelium ; Intestine ; Desquamation ; Restitution ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In situ loops of large bowel of anaesthetised rats were used to observe epithelial restitution following surface desquamation using solutions of bile salts. The treatment induced complete surface desquamation but no disruption of the basal lamina. There was evidence of, cell migration at 30 min, and a complete surface epithelium two h post treatment. Neither a continuous contact between migrating cells and the basal lamina, nor a complete covering of secreted mucus, appeared necessary for epithelial restitution to occur.
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  • 187
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    Urological research 16 (1988), S. 127-131 
    ISSN: 1434-0879
    Keywords: Microsurgery ; CO2 laser ; Neodymium Yag laser ; Vascular anastomosis ; Rat ; Tensile strength ; Histology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A comparative study was undertaken to investigate the application of a specially adapted microsurgical Neodymium Yag Laser system with a wavelength of 1,319 μm and a CO2 laser system for laser assisted microvascular end-to-end anastomosis (LAMA) of the rat femoral artery. Conventionally sutured anastomoses served as controls. Postoperative investigations included patency tests, light microscopy and tensile strength measurements. Both laser systems seem to be equally suitable for LAMA: The patency rates do not differ from those of sutured anstomoses and formation of microscopically small aneurysms occurred predominantly in control animals and only once in laser groups. The clamp time needed for LAMA was half the time that was needed for sutured anastomoses. Wound healing in all groups was similar with less fibrotic reactions and less foreign body granulomas in laser groups. At all intervals tensile strength was significantly higher for sutured anastomoses while differences between the CO2- and the ND: Yag-laser groups were not statistically significant. Potential applications in urology include microvascular anastomoses in erectile dysfunction, pediatric and reconstructive urology.
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  • 188
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    Research in experimental medicine 188 (1988), S. 115-121 
    ISSN: 1433-8580
    Keywords: Gastrin ; Rat ; Somatostatin ; Stomach
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Low concentrations of somatostatin and gastrin within or slightly above the range of physiologically circulating levels were perfused in the isolated, vascularly perfused rat stomach preparation. Somatostatin at 10 and 50 pg/ml significantly inhibited acetylcholine-stimulated gastrin secretion by 26% and 45%, respectively, whereas perfusion of 50 and 500 pg/ml exogenous gastrin did not modify gastric somatostatin secretion. Perfusion of somatostatin-antiserum significantly increased gastrin release by 235%. It is concluded that (1) somatostatin is a powerful inhibitor of the gastrin cell under in vitro conditions; the data are in accordance with a concept that endogenous somatostatin could act as a true hormone; (2) the secretory activity of the somatostatin cell is not significantly affected by circulating gastrin.
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  • 189
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    Research in experimental medicine 188 (1988), S. 267-276 
    ISSN: 1433-8580
    Keywords: Splenic autotransplantation ; Phenylhydrazine ; Malaria infection ; Rat ; Blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary After splenic autotransplantation both weight and blood flow of the regenerated splenic tissue are decreased. In addition, the protective function of the transplant is less compared to that of the normal spleen. In the present study, the red pulp of normal and transplanted splenic tissue was stimulated by injections of phenylhydrazine to increase the weight, the blood flow, and the protective function. After stimulation, the weight of the normal spleen increased to 900 ± 70 mg (control 530 ± 20 mg) and the transplanted tissue to 240 ± 70 mg (control 70 ± 20 mg). This enlargement was caused by an increase in the splenic red pulp. However, the relative blood flow decreased in both the normal spleen and the transplant to 50% of the normal value. To evaluate the protective function of the stimulated splenic tissue, normal, splenectomized and transplanted rats were infected withPlasmodium berghei. Despite the dramatic increase in the red pulp, neither the normal nor the transplanted animals showed a survival rate superior to that of the splenectomized animals. The mass of splenic tissue obviously does not correlate with the protective effect of the spleen in parasitic infections.
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  • 190
    ISSN: 1434-0879
    Keywords: Renal transplantation ; Rat ; Ultraviolet irradiation ; PUVA ; Pulsatile perfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Systemic photochemical pretreatment of a rat kidney donor with the photosensitizer 8-methoxypsoralen (8-MOP; 0.06 mg/kg intravenously, 10 min before graft removal) plus ex vivo longwave ultraviolet (UVA) irradiation of the kidney graft during simple hypothermic storage significantly prolonged survival time in allogeneic recipients. In contrast to these results, the present use of UVA irradiation during hypothermic pulsatile kidney perfusion using Euro-Collins® solution containing 8-MOP (0.06 mg/ml) did not prolong graft survival compared with untreated controls. Systemic application of 8-MOP to the kidney donor may be necessary for effective action of the combined photochemical treatment as a method of immunoalteration. The extended UVA irradiation time and the local use of 8-MOP in the preservation fluid had no effect on graft survival possibly because of inadequate tissue distribution of 8-MOP during both hypothermia and perfusion.
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  • 191
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    Urological research 16 (1988), S. 277-280 
    ISSN: 1434-0879
    Keywords: Electrical stimulation ; Stretching ; Time factor ; Bladder strip ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Distension of the human urinary bladder often causes prolonged impairment of its function. To investigate the effects of the duration of stretch on bladder smooth muscle the active length-tension relation, electrically evoked, was described in rat detrusor strips during a short-term and a long-term stretch. The amplitude of active tension increased at first and then decreased abruptly at greater stretch lengths, the maximum being at muscle lengths 230–250% (100%=resting length) in both types of stretches. When the strips had been at maximum length (300%) for three hours the amplitude was significantly decreased during release as compared to the amplitude found during stretch to the maximum length at comparable lengths. If the strips were released immediately from the maximum length the amplitude responded in an opposite manner. Therefore we conclude that the duration of stretching of bladder smooth muscle significantly affects its mechanical activity.
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  • 192
    ISSN: 1433-8580
    Keywords: Rat ; Intestinal ammoniagenesis ; Glutamine metabolism ; Small intestine ; Colon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The intestinal ammonium production and the intestinal uptake of circulating glutamine were investigated in anesthetized intact rats and rats with resected small intestine or colon by simultaneous measurements performed on portal and arterial blood. It was shown that ammonium release into the portal blood by the small intestine is of equal magnitude to that released by the colon, and that circulating glutamine participates in ammonium production by the small intestine. Increased levels of circulating glutamine induced by its i.v. infusion to intact rats were not accompanied by an increase in intestinal ammonium production.
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  • 193
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    Research in experimental medicine 188 (1988), S. 123-129 
    ISSN: 1433-8580
    Keywords: Acute experimental pancreatitis ; Sodium taurocholate ; Pancreatic enzymes ; Pancreatic morphology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sodium taurocholate pancreatitis in the rat is a frequently used experimental model for evaluating therapeutical regimes in this disease. It is, however, uncertain when treatment should be started, as the early phase of this experimental model and thus the time when the pancreatitis really develops is unknown. Serum and pancreatic enzymes, as well as pancreatic morphology, were therefore studied 5, 30, and 60min after induction of sodium taurocholate pancreatitis. It was found that increase in serum enzymes and decrease in pancreatic enzymes and morphological changes characteristic for acute pancreatitis develop as early as 5 and 30 min after induction of pancreatitis. Thus, therapy in this model may be started shortly after induction of acute pancreatitis.
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  • 194
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    Anatomy and embryology 177 (1988), S. 349-352 
    ISSN: 1432-0568
    Keywords: Pineal body ; Mongolian gerbil (Meriones unguiculatus) ; Rat ; Calbindin D-28K (vitamin D-dependent calcium binding protein) ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunocytochemical reaction for demonstration of calbindin D-28K has been performed in superficial pineal bodies of the Mongolian gerbil (Meriones unguiculatus) and the rat. Whereas in the Mongolian gerbil there were no clearly expressed calbindin immunoreactive cells, these were numerous in the rat pineal body. Here the calbindin-positive cells — probably pinealocytes — were disposed along capillaries. In view of the role of calbindin in binding and transporting calcium and regulating its intracellular levels, the absence of this protein in the gerbil pineal body has been interpreted as signifying the inability of pinealocytes to eliminate intracellular calcium with possible consequent formation of acervuli.
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  • 195
    ISSN: 1432-0568
    Keywords: Atrial specific granule ; Atrial natriuretic polypeptide ; Impulse conducting system ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study was performed to clarify the distribution of ANP-containing cells in the adult rat heart by immunostaining for ANP using antiserum against α-human ANP. ANP-immunoreactive cells were generally present in the atrial walls except for the sinoatrial node. In the ventricular walls, they were distributed in the impulse conducting system, particularly the left bundle branch, Purkinje fibers on the left side of the interventricular septum, and those in the false tendons in the left ventricle, while they were sporadically seen in the atrioventricular node and bundle of His. The immunoreactive cells contained specific granules that were positive for ANP. These findings demonstrate that ANP-containing cells are present in the atrial and ventricular walls.
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  • 196
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    Acta neuropathologica 76 (1988), S. 253-264 
    ISSN: 1432-0533
    Keywords: Cerebral ischemia ; Rat ; Hyperglycemia ; Postischemic seizures ; Substantia nigra
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study explores how hyperglycemia and enhanced tissue lactic acidosis influence the density and distribution of ischemic brain damage. Ischemia of 10-min duration was produced in glucose-infused rats by bilateral carotid clamping combined with hypotension, and the brains were perfusion-fixed with formaldehyde following recirculation of 3, 6, 12 and 18 h. After about 24 h the hyperglycemic animals developed seizures, and at that time two groups were added, one fixed prior to, and one after the onset of seizures. Similar experiments were made on normoglycemic animals with recirculation times of 1.5 to 96 h. After fixation the brains were embedded in paraffin, subserially sectioned and stained with celestine blue/acid fuchsin. In both normo- and hyperglycemic animals, neurons in the dentate hilus of the hippocampal formation and in the thalamic lateral reticular nucleus showed early and dense neuronal necrosis. In neocortex, hippocampal CA1 sector and caudoputamen, hyperglycemia shortened the delay before damage occurred and markedly enhanced the damage. Specific for the hyperglycemic animals was damage of the substantia nigra, pars reticulata (SNPR), manifest already at the earliest recovery periods studied; this finding is discussed in relationship to the role SNPR is assumed to play in preventing spread of seizure discharge.
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  • 197
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    Anatomy and embryology 177 (1988), S. 267-275 
    ISSN: 1432-0568
    Keywords: Septal nuclei ; Prenatal development ; Quantitative histology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Prenatal development of septal cell groups was studied in the rat on samples taken daily from the 14th day of gestation until birth. Coronal serial sections of brains were prepared in which the topography coordinates of septal nuclei were determined, their section profiles measured and their volumes calculated. The rat septum begins to develop on embryonic days 14–15. First the individual neurons start to differentiate, then cell groups characteristic for the adult are formed between days 14 and 17, which is followed by the delineation of nuclei. The only exception is the anterior subdivision of the lateral septal nucleus where the formation of the nucleus precedes the differentiation of its constituent cells. The individual nuclei start to develop at different times defined by a medio-lateral gradient of cell migration. By embryonic day 20 the formation of the nuclei can be considered as complete: all septal nuclei and their subdivisions are to be recognized and distinguished from each other.
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  • 198
    ISSN: 1432-0568
    Keywords: Primary afferents ; Muscle ; Anterograde tracing ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The sternomastoid muscle of the rat is divided into a white (dominated by fast-glycolytic twitch fibers) and a red (dominated by fast oxidative-glycolytic twitch fibers, but also containing slow-oxidative twitch fibers) compartent. Previous reports on exclusive location of muscle spindles in the red portion were confirmed. On the basis of anterograde labeling with horseradish peroxidase-wheat germ agglutinine conjugate (WGA-HRP) it was shown in this study that, in addition to muscle spindle compartmentalisation, there was also an exclusive occurrence of tendon organs in the red part of the muscle; moreover, fine afferents (III- and IV-afferents) were mainly distributed to this portion as well. Radioimmunassay studies revealed that this part of the muscle contained twice as much substance P as the white part. It could be shown by acetylcholinesterase (AChE) histochemistry that the myelinated fibers of the white branch to the muscle exclusively displayed high enzyme activity which is characteristic for motor fibers; on the other hand, in the branch to the red portion two classes of AChE-positive fibers were found: a large one with a peak in the alpha-range, and a small one with a peak in the gammarange. In addition, there was also a group of enzyme-negative (sensory) fibers. These results also indicate the red portion of the sternomastoid muscle to be its “sensory compartment”.
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  • 199
    ISSN: 1432-0568
    Keywords: LHRH ; Rat ; Maturation ; Sex-difference
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Luteinizing hormone-releasing hormone (LHRH) neurons were immunohistochemically studied in rats of both sexes at peripubertal ages. The number of immunoreactive LHRH neurons (irLHRH neurons) was counted in the brain region from the level of the septumpreoptic area to the level of the rostral part of the infundibulum in colchicine-treated male and female rats at 30 and 60 days of age. At 30 days, irLHRH neurons were more numerous in male rats than females. At 60 days, the number of irLHRH neurons in female rats increased to the level of male rats of the same age. In non-colchicine-treated rats, the count of irLHRH neuron was quite low. The difference in the number of irLHRH neurons between colchicine-treated and non-treated rats may be regarded as the activity of LHRH system. The difference in the number of irLHRH neurons was larger in male rats than in female rats at 30 days of age. On the contrary, at 60 days of age, the difference was larger in females than in males. LHRH contents were measured in the preoptic-anterior hypothalamic area (POA-AH), where LHRH neuronal perikarya are mainly located, and in the mid-hypothalamic area. LHRH content of the POA-AH in male rats at 60 days of age was not significantly different from that at 30 days of age. While, LHRH content in the POA-AH was greater in 60-day-old female rats at proestrous morning than that in 30-day-old females. At 30 days of age, male rats tended to contain more LHRH in the POA-AH than female rats. However, either at 30 days or at 60 days, no statistically significant differences were detected between male and female rats. In mid-hypothalamic area, LHRH content in 60-day-old male rats was greater than that in 30-day-old male rats. On the other hand, there was no difference in LHRH content between 30-day-old and 60-day-old female rats. At 60 days of age, LHRH content in male rats was greater than that in female rats. The present morphological findings and LHRH measurements suggest that the functional maturation of LHRH system occurred earlier in male rats than in female rats.
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  • 200
    ISSN: 1432-0568
    Keywords: Pancreatic islet ; Insulin ; Glucagon ; Ontogeny ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ontogenetic appearances of glucagon, insulin and tyrosine hydroxylase (TH) were immunohistochemically investigated on developing pancreatic islets of rats. Glucagon immunoreactivity appeared first in some epithelial cells (g-cells) of the dorsal anlage of the pancreas on day 11.5 of gestation. On day 12.5, g-cells increased in number manufacturing the primitive islets, in which some cells appeared to be immunoreactive for insulin (i-cells) and about 40% of g-cells indicated also a slight immunoreactivity for insulin (g/i-cells). Afterwards, all the islet cells, especially g-cells, increased in number, and almost half of g-cells were g/i-cells. After day 16.5 of gestation, numerical increase of the cells with insulin immunoreactivity exceeded that of the cells with glucagon immunoreactivity, and about one fifth of g-cells were g/i-cells. After 20.5 days, however, no g/i cells were found. On day 16.5 of gestation, the immunoreactivity for TH appeared in occasional cells of the islets, but the cells did not show immunoreactivity for glucagon or insulin. It is concluded that the progenitor cells of the pancreatic islets appear to synthesize both glucagon and insulin by day 20.5 of gestation, but differentiate giving rise to mature A and B cells of adult isoets afterward.
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