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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    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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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 178 (1988), S. 119-127 
    ISSN: 1432-0568
    Keywords: Neuronal differentiation ; Fascia dentata ; Granule cells ; GABAergic neurons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Golgi impregnation was used to study the dendritic differentiation of granule cells in the rat fascia dentata. The impregnated granule cells were gold-toned allowing for a fine structural study of the same identified neurons and of the input synapses onto their cell bodies and dendrites. Due to the long postnatal formation of these cells it was possible to describe a sequence of maturational stages coexisting on the same postnatal day (P5). Characteristic features of the dendritic development of granule cells were i) occurrence of varicose swellings along the dendrites, ii) growth cones on dendritic tips, iii) transient formation of basal dendrites, and iv) progressive development of dendritic spines. Incoming synapses on the differentiating granule cells were mainly found on dendritic shafts. Their membrane specializations were symmetric. At least some of these symmetric synapses were GABAergic because immunostaining of Vibratome sections from the same postnatal stage (P5) demonstrated a well-developed GABAergic axon plexus in the fascia dentata (antibodies against glutamate decarboxylase (GAD), the GABA synthesizing enzyme). Electron microscopy of the immunostained axon plexus revealed numerous GABAergic terminals that formed symmetric synaptic contacts, mainly on shafts of differentiating dendrites but also on cell bodies of granule cells. Our results thus indicate that the plexus of inhibitory GABAergic axons is already well developed at a stage when the target neurons, the granule cells, are still being formed.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 178 (1988), S. 155-159 
    ISSN: 1432-0568
    Keywords: Interhemispheric pathway ; Congenital anophthalmia ; Visual cortex ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In an effort to assess the innate capacity of the central visual system to specify corticocortical connectivity in the absence of retinal afferents, we examined the tangential distribution of callosal cells and terminations in posterior neocortex of congenitally anophthalmic rats. Although our results indicate that the callosal pattern is clearly anomalous in these rats, all features of the normal visual callosal pattern are recognizable in mutant rats, indicating that central visual pathways can generate many aspects of normal interhemispheric connectivity in the absence of input from the periphery. On the other hand, the presence of anomalies in the pattern indicates that the eyes are necessary to finetune the distribution of callosal connections at some developemental stage. Moreover, the fact that abnormalities in the callosal pattern of mutant rats are the same as those previusly described in rats enucleated at birth suggests that the eyes begin to exert their influence on callosal development after birth.
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  • 4
    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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  • 5
    ISSN: 1432-0568
    Keywords: Visual cortex ; VIP ; Synapse ; Spatial distribution ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the rat visual cortex vasoactive intestinal polypeptide (VIP)-containing structures were studied by means of light and electron microscopy and image analysis. VIP-immunoreactive axon terminals were found to form symmetric synapses with small dendritic shafts, dendritic spines and somata of pyramidal cells and interneurons. VIP-terminals often occured in pairs with VIP-negative, asymmetric synapses on the same postsynaptic structure. VIP-immunostained dendrites and perikarya were contacted by a purely asymmetric and a mixed population of VIP-negative terminals, respectively. Synaptic connections between two VIP-neurons are seldom as compared to the other types of VIP-synapses. Quantitative studies obtained by the image analysis of VIP-stained boutons and dendritic particles in light microscopic preparations suggest a distinct laminar distribution. Dendritic particles are most frequent in layers I–II, whereas axonal boutons have three laminar accumulations: at the border of layers I–II, in layer IV and layer VI. Together with previous results, the present findings argue for a non-random spatial distribution of VIP-boutons.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 178 (1988), S. 381-388 
    ISSN: 1432-0568
    Keywords: Ciliary necklaces ; Olfactory ; Vomeronasal ; Respiratory ; Development ; Freeze-fracturing ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Many cilium types have at their proximal base a particulated membrane structure, the so-called ciliary necklace. Necklaces of primary and secondary cilia of olfactory receptor cells and ciliated respiratory cells, and of primary cilia of olfactory supporting cells were studied as a function of embryonic age. Strand numbers in necklaces of primary cilia of these cell types do not differ, but they differ significantly from those of necklaces of secondary cilia. Primary cilia have 2 to 4, but most commonly 3, necklace strands. This is true for necklaces of primary cilia of 8 different nasal cell types: olfactory epithelial basal and glandular cells, vomeronasal receptor and supporting cells, and microvillous respiratory epithelial cells, in addition to the 3 cell types mentioned above. Comparison with other systems suggests that primary cilia resemble flagella of eukaryotic flagellates and spermatozoa of some invertebrates with respect to their number of necklace strands. Average numbers of necklace strands in secondary olfactory cilia increase from 3–4 at the 16th and 17th gestational days to 6–7 in adults. Those in secondary respiratory cilia increase from 2–3 at the 18th and 19th gestational days to 5–6 in adults. Longer cilia have more strands than shorter ones. Necklaces often have free strand endings, also in primary cilia, suggesting that they spiral. Comparing the present data with those in the literature suggests that necklace features occurring during reciliation differ from those of de novo ciliogenesis. Primary and secondary cilia share the following qualities: 1) Membrane regions above necklace strands can differ quite drastically from those below the strands. 2) Necklace particles are firmly associated with cytoskeletal elements underneath the ciliary membrane. Hence, necklaces in primary cilia and in developing and mature secondary cilia may, together with the cytoskeleton underneath the membrane, provide a barrier for lateral diffusion and a region of membrane attachment. The latter may help to determine the shape of cilia.
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  • 7
    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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  • 8
    ISSN: 1432-0568
    Keywords: Rat ; Development ; Diencephalon ; Neuromeres ; Sulcus limitans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The morphogenesis of the ventricular surface of the diencephalon of the rat was studied using scanning electron microscopy, cryostat serial sections and direct observations under a dissection microscope. Based on these observations a description is given of the neuromeres present within the prosencephalon and of the termination of the sulcus limitans. Two conclusions are reached. First, three neuromeres are present in the prosencephalon. Neuromere I consists of the telencephalon, the hypothalamic regions and the parencephalon anterius. Neuromere II is the parencephalon posterius, neuromere III the synencephalon. Second, the sulcus limitans terminates ventrally in the parencephalon posterius and does not continue towards the preoptic recess. No exact termination point of the sulcus limitans could be delineated.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 179 (1988), S. 89-96 
    ISSN: 1432-0568
    Keywords: Tendon ; Myotendinous junction ; Fibroblast ; Muscle overloading ; Hypertrophy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Overloading of rat plantaris muscles was produced by aseptic ablation of the synergists. The morphological changes occurring after 1 or 2 weeks were investigated at the light and electron microscopical level in the distal tendon of the plantaris and at the myotendinous junction. Sham-operated rats were prepared as controls. In the tendon, quiescent fibrocytes were replaced by activated fibroblasts displaying a vesicular nucleus with prominent nucleoli and an outstanding increase in cytomembranes, particularly the rough endoplasmic reticulum and the Golgi complex. The plasmalemma of the fibroblasts was modified by the presence of caveolae and the surbsurface cytoplasm contained many membrane-bound vacuoles. In the tendon, the collagen bundles were disrupted, resulting in the formation of empty longitudinally oriented spaces; in these spaces, as in the pericapillary areas, no inflammatory cells were observed. At the myotendinous junction, fibroblast activation was consistently observed in both control and overloaded specimens. At this level, the sarcolemma of the finger-like projections of muscle fibres presented many caveolae close to clusters of large subsurface vacuoles. These observations indicate that, at the beginning of the compensatory hypertrophy, the adaptative changes to overloading include a non-inflammatory reaction of the tendon characterized by enhanced collagen synthesis and intensive membrane renewal and recycling. From the mechanical point of view this reaction can impair the tendon resistance to stretch. At the myotendinous junction the increased membrane turnover of the sarcolemma and the fibroblast activation can be considered permanent phenomena consequent to the increased stress exerted upon the interface connecting the contractile apparatus to the stroma.
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  • 10
    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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  • 11
    ISSN: 1432-0568
    Keywords: Immunohistochemistry ; Choline acetyltransferase ; Olfactory bulb ; Modified glomerular complex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The main and accessory olfactory bulbs (MOB and AOB) of the rat were immunohistochemically stained with a monoclonal antibody against choline acetyltransferase (ChAT) in order to know the difference in the distribution patterns of cholinergic fibers between these two structures. A few ChAT-immunoreactive cell bodies were found in the superficial and middle parts of the external plexiform layer (EPL) of the MOB, in the granule cell layer (GCL) of the MOB, and in the GCL of the AOB. The frequency in appearance of these cells was 0.9 cells/section in the MOB and 0.3 cells/section in the AOB. While the glomerular layer (GL) and the superficial part of the EPL were most densely innervated in the MOB, the internal plexiform layer received the richest innervation in the AOB. There were no immunoreactive structures in the olfactory nerve layer of the MOB and in the vomeronasal nerve layer and glomerular layer of the AOB. In addition to a relatively homogenous distribution of cholinergic fibers in the MOB and AOB, there were several foci of very dense network of immunoreactive fibers at the posterior level of the OB. These foci formed a part of the modified glomerular complex that was recently identified using 2-deoxyglucose method and was presumed to be related to suckling behaviour in the neonatal rat.
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  • 12
    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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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    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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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 179 (1988), S. 109-127 
    ISSN: 1432-0568
    Keywords: Rat ; Inferior olive ; GABA ; Glutamate decarboxylase ; Cerebellar circuitry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Boutons presumed to use γ-aminobutyric acid as neurotransmitter (GABAergic boutons) were detected by glutamate decarboxylase (GAD) immunocytochemistry in all regions of the rat inferior olive. The remarkably high concentration of these boutons allowed a clear visualization of olivary subnuclei boundaries. Regional variations in GAD immunostaining intensity were observed within the nuclear complex and were graded both visually and photometrically. The regional staining variations, for the most part, followed subnuclei boundaries and olivary zonal compartments that have been delineated by the topography of climbing fiber projections. Some subnuclei were grouped by similar staining intensities. The beta nucleus and a medial region in the ventral fold of the dorsal accessory olive were most intensely immunostained, followed by the subnucleus c of the medial accessory olive. Lower staining intensities were observed in the dorsomedial cell column, the dorsal fold of the dorsal accessory olive and the dorsal cap. The lowest intensities were observed in the subnuclei a and b of the medial accessory olive, the ventrolateral outgrowth, the rostral lamella of the medial accessory olive, the principal olive, and the lateral part of the ventral fold of the dorsal accessory olive. The factors contributing to the variations in immunostaining intensity (bouton size and frequency of occurrence) were investigated. The largest boutons were observed in the beta nucleus. Intermediate sized boutons were observed in the dorsomedial cell column, dorsal cap and the dorsal fold of the dorsal accessory olive. The smallest boutons were present in the remaining regions of the inferior olive, including the principal olive, the rostral lamella of the medial accessory olive, and the ventral fold of the dorsal accessory olive. The medial region of the dorsal accessory olive ventral fold contained a higher density of GABAergic boutons than other regions. GABAergic bouton size and innervation density therefore largely accounted for the variations in GAD immunostaining intensity. This study provides a map of the rat inferior olive based on the distribution of GABAergic nerve terminals, and may serve as a basis for characterizing different GABAergic afferent systems in the inferior olive.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 178 (1988), S. 175-181 
    ISSN: 1432-0568
    Keywords: Liver development ; Adrenergic innervation ; Enzymic zonation ; Rat ; Spiny mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The development of noradrenergic innervation of rat liver was studied with a polyclonal antiserum against noradrenaline. Nerves are first seen in the larger portal vessels at day 1 after birth and reach their final distribution at 5 days after birth i.e. at the same time as the establishment of the acinar architecture and the heterogeneous distribution of NH3-metabolizing enzymes. The latter distribution of nerves is already seen at birth in the liver of the closely related but precocial spiny mouse. This shows that the onset of extrinsic sympathetic innervation is regulated by the developmental stage of the animal rather than by adaptation to extrauterine life. Chemical sympathectomy at birth with 6-hydroxydopamine did not eliminate the developmental appearance of heterogeneous distributions of NH3-metabolizing enzymes.
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  • 16
    ISSN: 1432-0568
    Keywords: Visual cortex ; VIP ; Neuronal types ; Axonal branching ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Vasoactive intestinal polypeptide (VIP)-immunoreactive cells in the primary visual cortex of the rat were classified on the basis of ramification pattern of cell processes. The distribution of cells over cortical layers, and proportions of cell classes relative to total cell numbers were evaluated by means of quantitative methods. Two main types of VIP-positive neurons, the bipolar and the multipolar were distinguished constituting 76% and 24% of the VIP populations, respectively. The axons of vertically oriented bipolars were observed to ramify within a column around the descending dendrite. By contrast, multipolar cells have a non-oriented ramification pattern. The two overlapping axonal systems form the VIP-innervation of the rat visual cortex.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 178 (1988), S. 309-326 
    ISSN: 1432-0568
    Keywords: Axons ; Cilia ; Microvilli ; Olfactory ; Respiratory ; Development ; Freeze-fracturing ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Olfactory axons and apical structures of olfactory epithelia and of nasal respiratory epithelia of rat embryos were studied with the freeze-fracture technique; adult tissue samples of the same sources were used for comparison. At the onset of epithelial differentiation (14th gestational day) intramembranous particle densities are the same for all structures in both epithelial types. During further development, particle densities in membranes of primary cilia remain lower than those in membranes of other apical structures. Otherwise, I found the following from the 14th to the 19th day of gestation.a. Olfactory receptor cells of embryos of all age groups have axons wherein the membrane particle densities are about half those of adults. These densities are always lower than those of dendritic ending structures. Dendritic endings with primary cilia have lower densities than endings with secondary cilia; densities mainly increase when the endings sprout secondary cilia. Adult values are reached at the 18th day of gestation.b. Olfactory supporting cells with only globular particles in their apices gradually transform into, or are replaced by, supporting cells which also have dumbbell-shaped particles in their apices. Particle densities are always higher in apical structures of supporting cells than in apical structures of receptor cells. Adult values are reached at the 17th day of gestation.c. Putative ciliated and ciliated respiratory epithelial cells have considerably lower particle densities in membranes of their apical structures than do olfactory epithelial cells. Of special interest is that this is also true for secondary respiratory and olfactory cilia; as soon as genesis of secondary cilia in either epithelial type begins, their membrane features differ. Also, in contrast to apical structures of the olfactory epithelium, particle densities in apical structures of the respiratory epithelium do not systematically change during pre-natal development, and resemble the density values of adults. An exception are the microvilli of the respiratory cells with secondary cilia, membranes of which have considerably higher particle densities in adults than in embryos. In conclusion: Transformations of olfactory receptor cell dendritic endings with primary cilia into endings with secondary cilia, and of olfactory supporting cells with globular particles in their apices into cells with dumbbell-shaped particles in their apices are accompanied by increases in the densities of their intramembranous particles. These developmental changes parallel the electrophysiological onset of olfactory receptor cell specificity.
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    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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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 61 (1988), S. 489-495 
    ISSN: 1432-0738
    Keywords: Fusarenon-X ; T-2 Toxin ; Jejunal absorption ; Monosaccharide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to delineate the effects of Fusarenon-X (FX) and T-2 toxin (T-2) on intestinal absorption of monosaccharide, jejunal absorption in vivo and uptake in vitro of 3-0-methyl glucose (m-glucose) and l-glucose were studied in rats. Jejunal absorption in vivo was assessed by determining the rate of appearance of the sugars in plasma of the mesenteric vein draining the jejunal segment, which was perfused with the medium containing radiolabelled m-glucose or l-glucose. Jejunal uptake in vitro was assessed by determining the m-glucose or l-glucose uptake by the everted jejunum taken from toxin-treated rats, m-Glucose absorption was reduced 1 or 3 h after either toxin was injected into the jejunal lumen. A reduction of m-glucose absorption was also noted after intravenous injection of the toxins, although the timing and magnitude of the reduction were slightly different from those seen after the luminal injection. These results suggest that both toxins impair the jejunal function relating to monosaccharide absorption in the early stages of intoxication. The reduction in m-glucose absorption was associated with a reduction in l-glucose absorption and unchanged or increased uptake of l-glucose. The active transport component, which was indicated by the difference between absorption or uptake of the two sugars, was also reduced in association with the reduction of m-glucose absorption. These results suggest that the toxins cause specific damage in the active transport system for monosaccharides on the one hand, and impairment of their diffusional movement from the epithelial layer to the mesenteric vein on the other.
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  • 20
    ISSN: 1432-0738
    Keywords: Rat ; Naphthalene ; Peroxidation ; Glutathi one peroxidase ; Superoxide dismutase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male, weanling Blue-Spruce rats were treated with naphthalene (p.o.) in defined dose increments up to 750 mg/kg body weight over 9 weeks. At necropsy, treated rats showed a 20% decrease in body weight compared to controls. Naphthalene treatment resulted in enhanced peroxidation (p〈0.001) only in the liver. This increased peroxidation was associated with reductions (p〈0.05) in the activity of the selenoenzyme glutathione peroxidase in hepatic cytosolic fractions and an associated increase (p〈0.05) in the selenium-independent glutathione peroxidase. No increase in peroxidation was observed in the lung, eye or heart of these rats and the activities of the selenoenzyme and the selenium-independent glutathione peroxidases were also unaffected by naphthalene in these organs. Naphthalene also did not affect superoxide dismutase activity in any of the organs examined. Thus, in addition to the known effects of naphthalene on tissue glutathione, naphthalene-induced reductions in the selenoenzyme glutathione peroxidase can also contribute to peroxidation in the liver and must be considered as a contributing factor in naphthalene toxicity in vivo.
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  • 21
    ISSN: 1432-0738
    Keywords: Acyclovir ; Embryotoxicity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Following three s.c. injections of acyclovir (100 mg acyclovir/kg) into rats on day 10 of pregnancy 19 litters were evaluated on day 21 of gestation and the effects were compared to the results obtained from controls (nine litters) which received the vehicle (0.1 N NaOH) only. The following results were obtained (treated group versus control group): 1) Implantations/litter: 11.2±1.3 versus 10.2±1.1; 2) resorptions/implantations: 27.7% versus 2.2%; 3) number of viable fetuses evaluated: 154 versus 90; 4) fetuses with anomalies of the skull: 78% versus 12%; 5) fetuses with anomalies of the vertebral column: 38% versus 13%; 6) gross-structural anomalies predominantly affected the skull and tail. The most frequently registered defects were: os tympanicum (smaller): 23%, os tympanicum (missing): 23%; missing tail: 7%; protruding tongue (15%); none of these defects were seen in the control fetuses. Postnatally we observed a high mortality rate among the offspring. From a total of 85 newborn (nine litters) we obtained 73 viable offspring (9.1±3.4); 81% of them had tail alterations. In the control group of eight litters (9.4±2.3) no tail alterations occurred. On day 21 postnatally 40 viable offspring were alive (mortality rate: 38.8%). Nearly all of these animals had visible alterations at multiple sites of their bodies; most frequently observed were: tail impairment, closed eyes, dragging hind-limbs, and urogenital alterations (e.g. testicular atrophy). These studies show for the first time that prenatal treatment with acyclovir induces gross-structural defects which persist postnatally. With the usually applied precautions during therapeutic use in pregnant women, the teratogenic potency of acyclovir seems to be small; however, acyclovir does have a teratogenic potential.
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  • 22
    ISSN: 1432-0738
    Keywords: (14C)-2-ethylhexyl acrylate ; Rat ; Distribution ; Elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The fate of (14C)-2-ethylhexyl acrylate was studied in adult male Wistar rats given an intravenous (i.v.) or intraperitoneal (i.p.) injection of 10 mg/kg (0.054 mmol/kg). The elimination of radioactivity from blood was bi-exponential, irrespective of the route of (14C)-2-EHA administration or the age (weight) of the rats. The first phase half-lives after i.v. and i.p. administration in 4-month-old rats were 30 and 60 min, in 7-month-old rats 115 and 130 min, respectively. The corresponding values for the slow-phase were 5 and 6 h, and 14 and 14h. Elimination of the radioactivity from tissues followed a pattern similar to that seen for blood. More than half of the administered radioactivity was exhaled as carbon dioxide. Exhalation of unchanged (14C)-2-EHA accounted for only 0.05% (i.v.) or 0.3% (i.p.) of the initial dose of radioactivity. The radioactivity excreted in the urine within the first 24 h posttreatment accounted for 7% (i.p.) or 14% (i.v.) of the initial dose, and only 2% was excreted as thioethers.
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  • 23
    ISSN: 1432-0738
    Keywords: Adriamycin ; Heart ; Kidney ; Liver ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of chronic adriamycin treatment on cellular defence mechanisms against free radicals has been determined in rats. To that end, the changes in vitamin E content, activity of superoxide dismutase, catalase and factors of the glutathione system were measured in heart, kidneys and liver after 24 and 52 days of treatment. Moreover, damage was assessed by measuring the activity of NADPH- and NADH-cytochrome c reductase. The results concerning the components of the oxidative defence systems in male rats showed reductions in the activity of superoxide dismutase and catalase in renal tissue and in factors of the glutathione system in liver tissue. In cardiac tissue an increased activity of catalase and elevated content of total glutathione were found. Vitamin E content was increased in liver and to a lesser extent, in kidneys. The activity of Se-dependent glutathione peroxidase sharply decreased only in liver. Major differences between male and female rats were not observed in renal and cardiac tissue, as far as protective factors were concerned. However, a decrease in catalase activity was detectable earlier in male kidneys. The protective factors in liver of female rats were far less susceptible to in vivo treatment with adriamycin, as compared to liver of male rats. Decreased activity of the cytochrome reductases was found in liver of male rats. In male renal tissue only cytochrome c reductase activity was significantly reduced. Male cardiac tissue showed no signs of biochemical damage, although from histological examination in a parallel study [J Natl Cancer Inst 76: 299–307 (1986)] lesions were evident. In female rats no damage was found in liver, kidneys and heart.
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  • 24
    ISSN: 1432-0738
    Keywords: Nephrotoxicity ; Cytostatic drug ; Celiptium ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Celiptium (N2-methyl-9-hydroxy-ellipticinium) is an antitumoral agent used to treat bone metastases from breast carcinomas. This new drug appeared to be of great interest because of the absence of hepato-or myelotoxicity. Three different investigators recently mentioned cases of celiptium-induced renal failure. We therefore undertook a study of renal function and morphology in female Wistar rats. Two single i.v. doses (10 or 20 mg/kg) were administered and animals were sacrificed 4, 8, 15, 28 and 60 days after injection. One group of rats received multiple doses, 5 mg/kg/week for 8 weeks. No mortality was observed. With the 10 mg/kg single dose creatinine clearance (Ccr) and urinary enzymes did not change, and tubular lesions were rare. With the 20 mg/kg single dose CCr decreased on day 4 and returned to normal on day 28. Urinary enzyme excretion (AAP, NAG, γGT) increased. Renal lesions were diffuse with tubular necrosis, luminal dilation and later (day 28) interstitial cellular infiltration. These lesions persisted on day 60 and appeared to be irreversible. Ultrastructural studies showed numerous large fat droplets in proximal tubular cells. Glycerol concentrations in renal cortex homogenates were increased while phospholipids are slightly decreased. With 5 mg/kg every week (multiple doses) Ccr decreased and tubular lesions similar to the observed with the 20 mg/kg single dose were seen. Thus celiptium induced dose-dependent nephrotoxicity in rats with prolonged tubular alterations. Since it has been shown that renal tubular cells metabolized celiptium in vitro into electrophilic intermediates, we suggest that free radicals and quinone derivatives may contribute to peroxidation of unsaturated fatty acids and play a role in the nephrotoxicity of the drug.
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  • 25
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    Archives of toxicology 62 (1988), S. 452-457 
    ISSN: 1432-0738
    Keywords: Orthophenylphenol ; Metabolites ; Buthionine sulfoximine ; Hepatotoxicity ; Nephrotoxicity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A single oral administration of orthophenylphenol (OPP, 1400 mg/kg; about half the LD50) to male Fischer 344 rats produced an elevation of serum transaminase activity 24 h later. Pretreatment with l-buthionine-S,R-sulfoximine (BSO, 900 mg/kg) in the OPP-treated rats potentiated the hepatic and renal damage which was accompanied by necrosis. Six hours after the administration of OPP (700 or 1400 mg/kg), hepatic and renal glutathione (GSH) levels decreased with increasing dosage. Hepatic GSH depletion with OPP was enhanced with BSO pretreatment and the recovery of GSH in both organs was slow in the high-dose OPP group. These results suggest that hepatic and renal damage is associated with a serious and prolonged GSH depletion. When either phenyl-p-benzoquinone (PBQ) or phenylhydroquinone (PHQ), which are intermediates of OPP, was administered orally to rats at 700 or 1400 mg/kg, the mortality with the high dose of PBQ was 75% at 24 h. The serum transaminase activity and UN level increased with the low dose of PBQ, accompanied by necrotic hepatocytes. The toxic effects of PHQ on kidney or liver were less than those on PBQ. These observations suggest that the liver and kidney may be target organs for toxic actions of a large dose of OPP and its intermediate, PBQ.
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  • 26
    ISSN: 1432-0738
    Keywords: Methylmercury ; Aminoacyl tRNA synthetase ; Brain ; Protein synthesis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The activities of six aminoacyl-tRNA synthetase species were determined using enzyme preparations partially purified from the brains of control and methylmercury (MeHg)-treated rats. The activities of Asp-, Leu- and Tyr-tRNA synthetases were significantly reduced in the brains of MeHg-intoxicated rats, whereas those of Lysand Met-tRNA synthetases remained unchanged. In contrast, the activity of His-tRNA synthetase was significantly increased in the symptomatic phase of MeHg intoxication. The activities of these six aminoacyl-tRNA synthetases in the control brains were affected to different extents on the direct addition of MeHg to the assay system in vitro. No positive correlation was observed between the in vivo and in vitro effects of MeHg on the enzyme activities. These results indicate that the aminoacylation of tRNA is one of the actions of MeHg, which leads to inhibition of protein synthesis, and it is suggested that the syntheses of cellular proteins may be modified in different ways by MeHg, depending on their amino acid compositions.
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  • 27
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    Archives of toxicology 61 (1988), S. 359-365 
    ISSN: 1432-0738
    Keywords: Butylated hydroxytoluene ; Nephrotoxicity ; Phenobarbital ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A single large dose of butylated hydroxytoluene (BHT, 1000 mg/kg) in male Fischer 344 rats produced some renal damage, reduced accumulation of p-aminohippuric acid in renal slices, proteinuria and enzymuria, in addition to hepatic damage. Further, prior administration of phenobarbital (80 mg/kg, i. p., daily for 4 days) in the high-dose BHT-treated male rats produced renal damage accompanied by slight tubular necrosis. The renal damage was confirmed by biochemical and histological changes. These changes were dose dependent, with a maximum at 24 h after BHT administration, but had returned to the normal range by 48 h. Female rats, on the other hand, were less susceptible to BHT-induced renal and hepatic damage than male rats. The results indicate sex differences in BHT-induced renal or hepatic damage.
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  • 28
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    Archives of toxicology 61 (1988), S. 373-377 
    ISSN: 1432-0738
    Keywords: Dibutyltin dilaurate ; Neurotransmitters ; Brainareas ; Behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Exposure to DBTL (20, 40 or 80 mg/kg body weight) caused a decrease in levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) at all treatment levels. Hypothalamus and frontal cortex appeared to be most affected, since levels of all the three amines examined showed changes in these areas. Maximum decrease of DA was found in corpus striatum, NA in pons medulla and of 5-HT in frontal cortex. These animals also showed a decrease in spontaneous locomotor activity and learning at all the doses. The data indicates involvement of hypothalamus and frontal cortical regions of the brain in the neurotoxicity of DBTL.
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  • 29
    ISSN: 1432-0738
    Keywords: Lysozyme ; Renal damage ; Urinalysis ; Radioimmunoassay ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The radioimmunoassay (RIA) as a high sensitive detection method for rat lysozyme (LZM) was established and applied to determine LZM excretion in urine from rats treated with tubulotoxic chemicals in order to establish a sensitive method of detecting minor renal damage. Rat LZM which showed a single protein band on sodium dodecylsulfate polyacrylamide gel electrophoresis was purified by ion-exchange chromatography and gel filtration. The assay sensitivity of the established RIA using the purified rat LZM was 4–256 ng/ml rat LZM and was about 20 times the turbidity method. The concentration of LZM in normal rat urine was 76.2±6.0 ng/ml (mean ± SE, n = 50) using the RIA. In urine containing more than 100 ng/ml LZM, a high correlation between the values determined by the RIA and those by the turbidity method was observed. However, egg white LZM, human urinary LZM and guinea pig urinary LZM were not detectable by the RIA. Using the RIA, it was ascertained that urinary LZM excretion began to increase on day 5 in rats treated with gentamicin (15 or 30 mg/kg/day sc for 17 days), during the 6–9 h period in the rats treated with mercuric chloride (1 mg/kg sc), and during the 0–3 h period in the rats treated with p-aminophenol (1 mmol/kg sc). These significant increases in LZM excretion were not detectable by the turbidity method; therefore, it was concluded that this RIA for rat LZM was very useful for detection of minor renal damage.
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  • 30
    ISSN: 1432-0738
    Keywords: Gentamicin ; Pregnancy ; Rat ; Fetus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract As part of our studies on the prenatal induction of renal dysfunctions in rats by gentamicin we measured maternal plasma levels of the drug. Additionally, the gentamicin concentrations in the plasma of rat fetuses after single s.c. injections of gentamicin were measured. The following results were obtained: 1) Non-pregnant rats excrete the drug faster than pregnant rats; 2) after a single s.c. injection of 110 mg gentamicin/kg body wt to six pregnant rats on day 21 of gestation the following pharmacokinetic variables were calculated: t1/2(inv): 27.0±6.1 min, t1/2(elim): 54.7±3.8 min, Cmax: 166.2±22.7 mg/l, tmax: 53±6.7 min, AUC: 431.7±53.4 mg/l×h; 3) plasma concentrations increase with the duration of pregnancy; 4) fetal plasma concentrations were determined between 45 and 660 min after single injections of 150 mg/kg to the dams. The concentrations showed minimum variation over this time period. Thus, the ratio of maternal to fetal plasma levels decreases drastically during this period; 5) 8 h after s.c. injection of 110 mg/kg to six dams (day 21 of gestation) individual plasma concentrations in the plasma of mother animals and in the plasma of 65 fetuses were determined. All fetal plasma samples showed higher concentrations than the corresponding maternal ones; 6) after multiple injections a significant increase in plasma concentrations can be seen. A considerable individual variance is obvious at all times and with both doses investigated; 7) since maternal plasma concentrations vary considerably in individual animals, especially after multiple injections, fetal exposure must also be variable in different litters. This would also affect the extent of postnatal dysfunction in various litters.
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  • 31
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    Experimental brain research 71 (1988), S. 291-297 
    ISSN: 1432-1106
    Keywords: ACTH ; Emotional response ; Motor activity ; Vasopressin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In an attempt to find whether vasopressin (VP) secretion is suppressed by learned emotional stress, we have given rats under a hypertonic condition simultaneously applied light and tone that had been paired previously with footshocks and have quantified immunoreactive VP (ir-VP) in the plasma. In a training session light (60 watt) and tone (2 kz) of 3-s duration which were paired with electric footshocks (50 Hz, 1-s duration) were given to rats 11 times at an interval of 30 s. Various lengths of time after the training, the rats were tested with light and tone, which were unpaired with footshocks and repeatedly applied every 15 s for 3 min in the box used for training. Hypertonic NaCl (0.5 M, 2 ml/ 100 g b. w.) was injected s. c. 30 min before testing to increase the basal level of plasma VP. After testing, plasma ir-VP was significantly less in the experimental group than in the 0-mA control group of rats that were trained without FS. The values for the experimental group were also significantly less than those of untested control rats that had been trained with FS but were not tested. Plasma osmolality and blood haemoglobin concentration were not significantly different between control and experimental groups. Plasma immunoreactive adrenocorticotrophic hormone (ir-ACTH) level was higher and motor activity as expressed by cumulative time period of body movement during testing was lower in the experimental group than in either of the control groups. The difference in plasma ir-VP between experimental and control groups was statistically significant two days but not seven days after training, whereas ACTH and motor activity in experimental groups were still significantly different from those in control groups seven days after training. The suppressive VP and augmentative ACTH responses to testing disappeared in the rats that had received light and tone repeatedly during the intervening period between training and testing. These data support the hypothesis that emotional stimuli suppress VP secretion.
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  • 32
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    Experimental brain research 70 (1988), S. 155-165 
    ISSN: 1432-1106
    Keywords: Sm1 cortex ; Receptive fields ; Rat ; Bilateral receptive fields ; Hindlimb
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Single cells in the primary somatosensory (Sm1) cortex were investigated for responses to bilateral hindpaw stimulation in Wistar rats anaesthetised by continuous intravenous administration of Althesin. Fifty-one percent of cells sampled (N = 134) responded to equivalent punctate mechanical stimuli delivered to both the contralateral and ipsilateral hindpaws under light anaesthesia. The distribution by cortical depth of cells with receptive fields (RFs) on both hindpaws was not significantly different from cells which had only contralateral RFs. No cell was found with a purely ipsilateral RF. For 86% of cells tested (N=44) the ipsilateral RF was partly or completely homologous with areas within the contralateral RF. The sizes of ipsilateral RFs were smaller on 66% of occasions when tested against their contralateral RFs. Modal latencies to ipsilateral mechanical stimulation were longer than to contralateral stimulation (34.1±9.1 ms (S.D) cf. 26.4±7.2 ms, N=44). Ipsilateral RFs were lost for 77% of cells tested following a 33% increase in anaesthetic infusion rate. Conditioning mechanical stimuli applied to the centre receptive field (CRF) on the ipsilateral hindpaw reduced or abolished a cell's responses to equivalent test stimuli applied to it's contralateral CRF with C-T intervals of 20–200 ms. Conditioning stimuli applied to the CRF contralateral to the cell reduced or abolished responses to test stimuli on the cell's ipsilateral CRF using C-T intervals of 0–900 ms. Responses in one cortex to stimulation of the ipsilateral hindpaw were unaffected by elimination of responses from the same hindpaw in the opposite contralateral Sm1 cortex, where responses had been suppressed by topical Lignocaine administration. Retrograde transport of horseradish peroxidase from hindpaw Sm1 cortex labelled many cells in homolateral thalamus, but failed to label cells in the entire forebrain contralateral to the injection site. It is concluded that direct crossed thalamocortical and callosal Sm1-Sm1 pathways do not contribute to the production of hindpaw ipsilateral receptive fields.
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  • 33
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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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  • 34
    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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  • 35
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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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  • 36
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    European archives of oto-rhino-laryngology and head & neck 245 (1988), S. 136-141 
    ISSN: 1434-4726
    Keywords: Tympanic membrane structure ; Topical anesthetics ; Emla ; Rat ; Guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A eutectic mixture of two anesthetic solutions is that of lidocaine and prilocaine, which is available commercially as Emla (eutectic mixture of local anesthetics). This solution is commonly used in clinics in superficial skin surgery and when inserting intravenous catheters, and we also wanted to determine its surface effects when applied onto the tympanic membranes (TM) of rats and guinea pigs as animal models. The animals were observed by otomicroscopy for 2 weeks up to 5 months after administrations of the anesthetic solution. Tissue specimens were then obtained for light microscopy and fine structural analysis. The application of Emla caused minor structural changes to the rat TM, but hardly any alterations to that of the guinea pig. The changes displayed were an overall increased thickness, with typical submucosal edema but only slight epithelial reaction. In comparison with previous results with lidocaine, phenol and Bonain's solution, Emla seemed to be harmless to the structure of the TM. However, the efficacy of Emla as a topical TM anesthetic remains to be proved in future clinical trials.
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  • 37
    ISSN: 1432-0738
    Keywords: Acyclovir ; Prenatal toxicity ; Rat ; Viru-statics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pregnant rats were treated during organogenesis with s.c. injections of acyclovir and the embryos were evaluated on day 11.5 of gestation (crown-rump length, somites, protein content, score, abnormalities, histological examination). After eight injections of 50 mg/kg body wt on days 9, 10, and 11 of pregnancy a reduction of the crownrump length was noticed. After 100 mg/kg this effect was more pronounced. With two or three applications of this dose on day 10 specific embryonic abnormalities were visible: the shape of the head was abnormal, the width of the skull had decreased resembling a beak-like visceral cranium. With a single administration of 200 mg/kg on day 10 we found a similar but slightly more pronounced outcome. A drastic change of all variables was obtained after eight injections of 100 mg/kg on days 9, 10, and 11. Comparatively we measured maternal plasma concentrations of acyclovir 1 h after the administration of 50, 100 or 200 mg/kg body wt. After an injection of 50 mg/kg on days 9, 10, and 11 of gestation (three injections/day) the plasma levels ranged from 19.1 to 40.0 mg/l (1 mg/l = 4.44 μM). No cumulation was observed. In contrast, a cumulative effect was detected following a dose of 100 mg/kg. After the first injection of this dose a mean value (± SD) of 60.3±14.7 mg/l (n = 16) was obtained. In this case a third injection increased the mean plasma level to 124.6±16.6 mg/l (n = 5). Further injections, however, led to decreasing levels. One hour after administration of 200 mg/kg body wt acyclovir levels ranged from 120.0 to 163.9 mg/l. We conclude that acyclovir, at doses leading to plasma concentrations well above the therapeutic level in the dam, interferes with the embryonic development in the rat. Acyclovir induces typical gross structural abnormalities which have been first observed using a whole embryo culture system.
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  • 38
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    International journal of biometeorology 32 (1988), S. 17-20 
    ISSN: 1432-1254
    Keywords: Epilepsy ; Electromagnetic fields ; Rat ; Audiogenic seizure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Abstract In order to study the possible association between epileptic seizures and natural electromagnetic fields, 32 female audiogenic seizure (AGS)-susceptible rats were exposed to simulated 10 kHz and 28 kHz atmospherics and to a sinusoidally oscillating magnetic field with a frequency of 100 Hz and field strength of 1 A/m. After the electromagnetic exposure, seizures were induced in the rats with a sound stimulus. The severity of the seizure was determined on an ordinal scale, the audiogenic response score (ARS). The time from the beginning of the sound stimulus to the onset of the seizure (seizure latency) and the duration of the convulsion was measured. No differences from the control experiments were found in the experiments with simulated atmospherics, but the 100 Hz magnetic field increased the seizure latency by about 13% (P〈0.02). The results do not support the hypothesis that natural atmospheric electromagnetic signals could affect the onset of epileptic seizures, but they suggest that AGS-susceptible rats may be a useful model for studying the biological effects of electromagnetic fields.
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  • 39
    ISSN: 1432-1254
    Keywords: Atmospherics ; Carrageenan inflammation ; Rat ; Susceptibility ; Correlations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Abstract Between the mean daily density of 28 kHz atmospherics and the onset of epileptic fits there is a highly significant correlation coefficient (r) of 0.30; there is a negative coefficient of −0.20 between the fits and the mean daily density of 10 kHz atmospherics. The onset of heart infarction is correlated with 28 kHz atmospherics (r=0.15). Furthermore, we have discovered that sudden deafness is also correlated with certain configurations of atmospherics. In this paper we report the following correlation coefficients between the inflammatory reaction of rats to a carrageenan injection (rci) into a hind paw and the mean daily pulse rate of atmospherics of the same day:r=0.49 for the 8 kHz atmospherics (P〈0.02) andr=0.44 for the 10 kHz atmospherics (P〈0.04). The correlations between rci reaction and other atmospherics (12 and 28 kHz) are smaller and not significant. By the method of multiple linear regression we found a multipleR=0.54 between rci reaction and the 8 and 10 kHz atmospherics (the regression function for the rci reaction is 0.15+0.004×8 kHz+0.002×10 kHz,P〈0.05).
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  • 40
    ISSN: 1619-7089
    Keywords: MIBG ; Monoamine uptake ; Blood platelets ; Rat ; 6OH-DA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The uptake of MIBG, a scintigraphic agent widely used in the detection of APUD tumors, was studied with a pharmacological approach on an in vitro and an in vivo models. MIBG as well as norepinephrine (NE) was taken up by human blood platelets, a model for presynaptic nerve endings amine uptake, with a thermodependant mechanism. MIBG and NE uptake was inhibited by desimipramine and reserpine. However, MIBG but not NE uptake was inhibited by fluvoxamine, a serotonin (5HT) uptake inhibitor. This suggests that MIBG is a NE and also a 5HT uptake tracer which involves uptake one and vesicular storage mechanisms. In rats treated with 6-hydroxydopamine to induced a chemical sympathectomy, we observed an inhibition of uptake similar for MIBG and NE in the heart, the salivary glands and the spleen, but no effect was observed in the liver. Some clinical inferences to best investigate specific monoamine uptake are drawn from these results.
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  • 41
    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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  • 42
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    Pflügers Archiv 413 (1988), S. 62-66 
    ISSN: 1432-2013
    Keywords: Erythropoiesis ; Erythropoietin ; Renal artery constriction ; Hypoxia ; Kidney ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It is generally assumed that the O2 supply to the kidneys is the major determinant of the synthesis of erythropoietin (Ep). In the present study, the O2 supply of the kidneys of rats was lowered by the reduction of renal blood flow (rbf). Plasma Ep was determined after about 18 h of bilateral application of Goldblatt clips with graded inner diameters. The results were compared to findings in anemic rats, in which the systemic O2 supply was lowered by exchange transfusion of blood with plasma. We found a linear correlation between Ep levels in plasma and the degree of reduction of rbf. However, there was an exponential relationship between Ep levels and the concentration of hemoglobin in blood. In addition, the elevation of plasma Ep was only moderate, when rbf was reduced (maximum 0.07 IU Ep/ml plasma). The increase in Ep concentration was much more pronounced in anemia (up to about 7 IU Ep/ml plasma). From these results it may be concluded that decreasing oxygen supply to the kidney through reduction in renal blood flow (ischemic hypoxia) is less effective in increasing erythropoictin production than reducing the hemoglobin concentration (anemic hypoxia). The possibility must be considered that the increase in renal production of erythropoietin due to anemic hypoxia is triggered by one or more extrarenal signals.
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  • 43
    ISSN: 1432-2013
    Keywords: Chloride channel ; Rat ; Skeletal muscle ; Stereoisomers ; 2-(p-chloro-phenoxy) isobutyric acid ; Clofibric acid ; Myotonia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The S-(−) isomers of a series of clofibric acid analogs produced only a block of chloride conductance of rat skeletal muscle fibers with increasing concentrations until block was nearly complete. The R-(+) isomers, on the other hand, at low concentrations increased chloride conductance by as much as 9% to 39% and at higher concentrations decreased chloride conductance, but never by more than 27% of the control value. The actions of the enantiomeric pairs to either produce or inhibit myotonic excitability paralleled their ability to block or increase chloride conductance, respectively.
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  • 44
    ISSN: 1432-1335
    Keywords: Prostate ; Rat ; Electron microscope
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prostate epithelium of rats which received repeated cadmium chloride (CdCl2) injections showed a gradual disruption of structural differentiation. Electron microscopy studies revealed severe changes in the ultrastructure affecting all epithelial cell organelles, particularly the nuclei, rough endoplasmatic reticulum, the golgi apparatus, and mitochondria. The cells infiltrating the stroma contained secretory vacuoles and their nuclear evaginations on the invasion front showed similarities to ultrastructural pathological changes in man. Examination of the ventral prostate following oral CdCl2 administration revealed changes ranging in severity up to dysplasia, but there was no evidence of carcinoma.
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  • 45
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    Experimental brain research 72 (1988), S. 443-449 
    ISSN: 1432-1106
    Keywords: Protein kinase C subspecies ; Immunocytochemistry ; Visual cortex ; Hippocampus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Monoclonal antibodies against type II and type III subspecies of protein kinase C PkC(II/III) were used to map the distribution of these isoenzymes in the visual cortex (area 17), hippocampus and dentate gyrus of the rat. PkC(II/III)-immunocytochemistry resulted in a specific staining of neuropil and of neuronal somata with their proximal dendrites. The majority of immunopositive cells exhibited a punctate distribution of reaction product, while only a few neurons were homogeneously labeled. In the visual cortex stained neurons were distributed throughout all laminae and reached a particularly high density in layers II/III. Moreover, PkC(II/III)-positive neurons were found within the strata pyramidale and radiatum of the hippocampus proper and in the stratum granulosum, the subgranular zone and the hilar region of the dentate gyrus. The present results suggest that PkC(II/III)-positive neurons constitute a distinct population of both projection and local circuit neurons that are not exclusively associated with any one neurotransmitter system.
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  • 46
    ISSN: 1432-1106
    Keywords: Extracellular Na+ concentration ; Quisqualate (quis) ; N-methyl-D-aspartate (NMDA) ; Tetrodotoxin (TTX) ; Hippocampal area CA1 ; Rat ; Extracellular Ca2+ concentration ; Extracellular Mg2+ concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Decreases in extracellular sodium concentration ([Na+]o) and associated slow negative field potentials (fp's) were monitored with double barreled sodium sensitive/reference microelectrodes in area CA1 of rat hippocampal slices during iontophoretic application of the glutamate receptor agonists N-methyl-D-aspartate (NMDA) and quisqualate (quis). The effects of lowering [Ca2+]o on these signals were compared to those of lowering [Mg2+]o. Both NMDA- and quis-induced decreases in [Na+]o of up to 60 mM and in the fp's of up to 8 mV. Decreasing [Mg2+]o enhanced NMDA-induced signals, whereas quis-induced signals were unaffected. Lowering [Ca2+]o also enhanced NMDA signals, although somewhat less than lowering [Mg2+]o. This effect was still present, even when voltage dependent Na+ currents were blocked by 10-7 tetrodotoxin. Interestingly, quis-induced signals could be enhanced in a low Ca2+ medium as well, but only when high quis concentrations were used. The results suggest that, during the sorts of large decreases of [Ca2+]o observed during seizure activity, activation of NMDA receptors is facilitated.
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  • 47
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    Experimental brain research 72 (1988), S. 71-82 
    ISSN: 1432-1106
    Keywords: Cholinergic-specific ganglioside ; Cholinergic neurons ; Chol-1 ; Spinal cord ; Brain ; Retina ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous work from this laboratory has identified gangliosidic surface markers specific for cholinergic neurons. Antibodies to these markers, collectively designated Chol-1, induce complement-mediated lysis of the cholinergic subpopulation of synaptosomes and provide the basis for a new immunocytochemical method for staining cholinergic neurons in rat, guinea pig and human material. The specification and localization of immunocytochemical staining for Chol-1 was investigated in selected areas of the rat central nervous system. The antigen was typically expressed on all neurons previously identified as being cholinergic using monoclonal antibodies to choline acetyltransferase. At spinal levels Chol-1 was present on large and smaller cell bodies in the ventral horn motoneuron area. The preganglionic sympathetic neurons in the thoracic intermediolateral nucleus were also Chol-1-positive. Nerve terminal-like staining was observed in association with stained large Chol-1 positive and smaller unstained Chol-1 negative neurons, and in lamina I and III of the dorsal horn. In the mesencephalon, motoneurons of the oculomotor and trochlear nucleus, as well as neurons within the pedunculopontine tegmental nucleus and the red nucleus were Chol-1-positive. In addition visceromotoneurons of the Edinger-Westphal nucleus were stained with anti Chol-1 antibodies. In the basal forebrain the antibodies gave a positive reaction on well known cholinergic neurons in the vertical and horizontal limbs of the diagonal bands of Broca and the medial forebrain bundle. In agreement with studies using antibodies to choline acetyltransferase, a small sub-population of neostriatal neurons (1–2%) was Chol-1-positive. In the rat retina, both anti-Chol-1 and anti-choline acetyltransferase antibodies gave rise to a nerve terminal-like staining in the same bands within the inner plexiform layer. The anti-Chol-1 antibodies also stain normal and pathological human material and could have a useful application in human neuropathology.
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  • 48
    ISSN: 1432-1106
    Keywords: Adult hypothyroidism ; Dendritic spines ; Pyramidal cells ; Cerebral cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have previously shown (Ruiz-Marcos et al. 1980, 1982) that thyroidectomy (T) performed in rats at 40 days of age, well past the neonatal period of development, results by 80–90 days of age in a decrease of the number of spines along the shaft of pyramidal neurons with the cell body in layer V in the visual area of the cerebral cortex. We have here studied how soon after the operation an effect on spine number and distribution may be observed. We have found that the response of these neurons to T is very rapid: a decrease in the number of spines/shaft between T and age-paired controls (C) rats is statistically significant by the earliest period of observation, namely 5 days after T. These results may be related to those of Dembri et al. (1983) showing that T performed in adult rats decreases the activity of Type I RNA polymerase by 5 days after the operation. It is possible that T impairs the synthesis of some compound(s) necessary for the formation and maintenance of spines. The present results suggest that spine number is not a fixed structure of the apical shaft once brain development is over, but is in a state of continuous formation and degradation. We have further observed that the effect of T performed at 40 days of age is more pronounced in the distal part of the shaft than on the rest, a result similar to that found after neonatal T (Ruiz-Marcos et al. 1982). However, contrary to findings after early hypothyroidism, T at 40 days of age does not distort the distribution of spines along the shaft.
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  • 49
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    Psychopharmacology 94 (1988), S. 115-118 
    ISSN: 1432-2072
    Keywords: Clozapine cue ; Drug discrimination ; Acetylcholine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to discriminate clozapine (CLZ; 5.76 mg/kg, IPt-30 min) in a two-lever operant task in which responding on the correct lever was reinforced with water under a fixed ratio 32 schedule. The ED50 of CLZ was 1.1 mg/kg. The CLZ cue was generalised to atropine (ED50=8.7 mg/kg), scopolamine (ED50=0.37 mg/kg) and fluperlapine (ED50=4.0 mg/kg), but not to non-cholinergic compounds, i.e. buspirone, diazepam, ketanserin, prazosin or SCH 23390. The peripherally-acting muscarinic antagonist methylscopolamine did not substitute for CLZ. Furthermore, the CLZ cue was marginally attenuated byd-amphetamine; a high dose of oxotremorine (1 mg/kg) appeared to block the CLZ cue (to 22%). However, this effect could not be evaluated statistically due to an insufficient number of animals responding. These results may indicate that the discriminative stimulus effects of CLZ primarily involve antagonism of central muscarinic acetylcholine receptors.
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  • 50
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    Psychopharmacology 94 (1988), S. 161-166 
    ISSN: 1432-2072
    Keywords: Hangover ; Thermoregulation ; Tolerance ; Ethanol ; Stress ; Compensatory reactions ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The recent finding of rebound hyperthermia in rats on the day after a single IP injection or oral intubation of ethanol was confirmed. In our studies, body temperature measured by rectal probe was significantly decreased for 8 h after 2.5 g/kg ethanol IP and was then significantly elevated 16–24 h after injection; increased vocalization during handling at 24 h was also found. However, rats isolated in a sound-attenuation chamber with remote temperature measurement showed no hyperthermia even though they were hypothermic during intoxication. The results do not support the hypothesis that rebound hyperthermia was caused by either a disruption of circadian rhythms, or by a mild abstinence syndrome alone. Instead, it appears that external stimuli, perhaps related to stress or associated with ethanol administration, are necessary on the day after a moderate dose of ethanol to produce the hyperthermia. Like hangover in humans, hyperthermia was reduced in rats made tolerant to ethanol: both the hypothermia and the rebound hyperthermia were significantly lower on the day after the 12th alternate-day ethanol injection than after the first injection. The aftereffects in rats of acute intoxication are, by definition, hangover signs, and they resemble hangover in humans in several ways, but their relevance as an animal model of hangover remains to be determined.
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  • 51
    ISSN: 1432-2072
    Keywords: Dopamine ; Self-administration ; (+) Amphetamine ; Amygdala ; Nucleus accumbens ; 6-OHDA ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of 6-OHDA lesions of dopamine terminals within the amygdala were investigated on i) (+) amphetamine-induced locomotor hyperactivity and ii) the acquisition of intravenous self-administration of (+) amphetamine. The lesioned rats exhibited increased locomotor activity in response to (+) amphetamine (0.75 and 1.5 mg/kg), but not at the higher dose (3 mg/kg). Self-administration of (+) amphetamine was also significantly greater than in controls. Biochemical analysis of the 6-OHDA-induced lesions of the amygdala indicated increased turnover of dopamine (DOPAC/DA) in the nucleus accumbens. We hypothesize that the behavioural effects were mediated by amygdala-accumbens interactions.
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  • 52
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    Psychopharmacology 94 (1988), S. 227-231 
    ISSN: 1432-2072
    Keywords: Adrenaline ; Naloxone ; Passive ; Avoidance ; Retention ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The possible involvement of endogenous opioid peptides in the development of the facilitatory effect of adrenaline on memory has been investigated. For this purpose post-training administration of adrenaline and/or naloxone was carried out in rats tested in an inhibitory avoidance paradigm and subjected or not to pre-training (extensive familiarization with the training situation prior to the acquisition trial). Adrenaline injected subcutaneously in a dose of 500 μg/kg facilitated retention performance in rats both subjected or not to pre-training. Naloxone administered SC (400 μg/rat) did not influence retention behaviour in rats subjected or not to pre-training, nor did ICV (0.80 ng/rat) administration. Interestingly, the opiate antagonist when injected SC (400 μg/rat) prevented the facilitatory effect exerted by adrenaline in pretrained as well as in not pre-trained rats. However, ICV administration of naloxone (0.80 μg/rat) dit not influence the behavioral effects exerted by the bioamine. These data suggested a role of endogenous opioid peptides on the facilitatory effect of adrenaline on memory, possibly independent of novelty factors and thus of the brain β-endorphin system. In addition, our results point to the periphery as the most likely site for such interaction.
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  • 53
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    Psychopharmacology 94 (1988), S. 254-258 
    ISSN: 1432-2072
    Keywords: Anorexia ; Feeding ; Hyperphagia ; Morphine ; Naltrexone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The delayed suppression of feeding caused by morphine was investigated in the rat. A single injection of morphine evoked a triphasic influence on feeding: a brief (1 h) severe anorexia was followed by hyperphagia (3 h) and a mild (20%) yet persistent (4–24h) anorexia. This latter anorexic effect was at least partially naltrexone reversible, and the duration of this antagonism (8 h) was longer than that of naltrexone's anorexic effect (4 h). Delayed morphine anorexia cannot be ascribed to morphine's initial stuporific influence, and it was not dependent upon previous feeding or deprivation. It was not due to gastric distension. The specificity and significance of this anorexia is discussed.
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  • 54
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    Psychopharmacology 94 (1988), S. 248-253 
    ISSN: 1432-2072
    Keywords: Bremazocine ; EKC ; Forward locomotion ; Grooming ; Open field ; Rat ; Rearing ; Tifluadom ; U-50,488H
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An observational analysis of the effects of four kappa-opioid agonists on forward locomotion, rearing and grooming displayed by rats in a novel open field was undertaken. The doses of agonists used corresponded to those previously found to produce changes in food consumption. Ethylketocyclazocine (0.1 and 1 mg/kg), bremazocine (0.01 and 0.1 mg/kg) and tifluadom (0.3 and 3 mg/kg) exerted suppressant effects on all the activities monitored. Grooming behaviour appeared to be particularly sensitive to this action, being virtually abolished by the larger doses of these compounds. In contrast, the selective kappa agonist U-50,488H (0.1–3 mg/kg) only attenuated grooming at the two highest doses tested (1 and 3 mg/kg). None of the agonists tested produced stimulation of open field activity during the 1-h study. Reductions in activity occurred at doses previously found to increase and decrease food intake. It was therefore concluded that the hyperphagia induced by kappa agonists was not part of a more general behavioural activation, whilst reductions in food consumption probably result from a non-specific behavioural depression.
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  • 55
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    Psychopharmacology 94 (1988), S. 359-364 
    ISSN: 1432-2072
    Keywords: Serotonin synthesis ; Dopamine synthesis ; RU-24969 ; Anxiety ; Antidepressant activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The regional brain synthesis of serotonin (5-HT) and dopamine (DA) was studied in rats after various doses of 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU-24969), a 5-HT1 receptor agonist. The potential anxiolytic and antidepressant properties of the compound were examined as well. RU-24969 0.62 mg/kg significantly reduced 5-HT synthesis in the nucleus accumbens and hypothalamus, while with 1.25 and 2.5 mg/kg the effect was also seen in striatum, hippocampus, brainstem and cortex. RU-24969 2.5 and 5 mg/kg had no effect on DA synthesis in the striatum, while 5.0 mg/kg significantly increased it in the nucleus accumbens. At doses of 2.5 and 5.0 mg/kg the drug increased the motor activity of rats measured during 1 h in activity cages while 0.625 and 1.25 mg/kg had no effect. Doses ranging from 0.62 to 2.5 mg/kg RU-24969 significantly reduced unpunished responding in a test of conditioned suppression of drinking. Doses of 1.25 and 2.5 mg/kg also reduced punished responding. Finally, of various doses only 2.5 mg/kg RU-24969 significantly reduced the duration of immobility of rats in the forced swimming test but the effects were due to running around the cylinder rather than to escape attempts. In conclusion, RU-24969 reduced 5-HT synthesis in all brain areas examined, with a preferential effect for the nucleus accumbens and the hypothalamus. At higher doses, there was also a specific increase in DA synthesis in the nucleus accumbens. The compound raised the level of activity of rats but no clear evidence of any potential anxiolytic or antidepressant properties has been obtained.
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  • 56
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    Psychopharmacology 95 (1988), S. 151-156 
    ISSN: 1432-2072
    Keywords: Apomorphine ; Amphetamine ; Strychnine ; Yohimbine ; Acoustic startle reflex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were presented with noise bursts alone or noise bursts 60 ms after presentation of either a 60 dB or an 80 dB prepulse after injection of the dopamine agonists apomorphine (3 mg/kg) or d-amphetamine (4 mg/kg), the glycine antagonist strychnine (1.5 mg/kg) or the α2 antagonist yohimbine (5 mg/kg). Presentation of prepulses inhibited startle, with greater inhibition following an 80 dB versus 60 dB prepulse. Apomorphine, d-amphetamine and strychnine increased overall startle levels but did not attenuate prepulse inhibition, since the absolute change in startle following prepulse presentation was significantly greater after administration of these drugs. A lower dose of apomorphine also increased startle but had no effect on prepulse inhibition using test intervals of 10, 60, 100, 200 or 1000 ms. While these drugs did decrease per cent prepulse inhibition, this seemed wholly attributable to their increasing overall startle levels, rather than a real attenuation of prepulse inhibition. Yohimbine did not alter either startle baseline or prepulse inhibition. The results do not support the conclusion that overactivity of dopamine systems attenuates prepulse inhibition and, in addition, suggest that prepulse inhibition does not result from activation of either glycine or norepinephrine projecting to α2 adrenergic receptors.
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  • 57
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    Psychopharmacology 95 (1988), S. 231-236 
    ISSN: 1432-2072
    Keywords: Latent inhibition ; Early handling ; Haloperidol ; Amphetamine ; Male ; Female ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Latent inhibition (LI) is a behavioral paradigm in which nonreinforced pre-exposure to a stimulus retards subsequent conditioning to that stimulus. The development of LI is considered to reflect learning not to attend to, or ignore, irrelevant stimuli. In our previous studies investigating the effects of early handling on LI, we have shown that normal LI was obtained in handled males and females, as well as in nonhandled females. In contrast, nonhandled males failed to show LI. This finding pointed to a long-term attentional deficit in nonhandled males. Since there is evidence that the development of LI is mediated by the dopaminergic system, the present experiments tested the possibility that the attentional deficit of nonhandled males may be related to a dopaminergic dysfunction. Experiment 1 tested whether the administration of haloperidol, which was shown to enhance LI in normal animals, would reinstate the LI effect in nonhandled males. Infantile handled (Days 1–22) and nonhandled male and female rats were tested in maturity in the LI paradigm, using a conditioned emotional response procedure. Experiment 2 tested the locomotor response of handled and nonhandled males to 0.3, 1 and 2.5 mg/kg d-amphetamine. Experiment 1 showed that handled males, handled females and nonhandled females showed a normal LI effect, whereas nonhandled males failed to develop LI. Haloperidol enhanced LI in all the groups, but this effect was most dramatic in nonhandled males, in which the drug reinstated LI. Experiment 2 showed that nonhandled males exhibited a reduced locomotor response to d-amphetamine.
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  • 58
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    Psychopharmacology 95 (1988), S. 413-417 
    ISSN: 1432-2072
    Keywords: DRL-schedule ; Imipramine ; Mianserin ; Idazoxan ; Yohimbine ; Amphetamine ; α2-Adrenoceptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have reported that antidepressant drugs exert specific effects on responding maintained by DRL schedules of reinforcement, giving rise to increased frequencies of reinforcement. In order to investigate whether the α2-adrenoceptor antagonist idazoxan would produce similar effects, the actions of this compound were compared with those of yohimbine, imipramine, mianserin and d-amphetamine in rats trained to lever press for food reinforcement on a DRL 60-s schedule. Neither imipramine nor mianserin produced any effects on response rate or reinforcement frequency, except at the highest doses. In contrast, both idazoxan and yohimbine gave rise to dose-related increases in rates of responding and consequent decreases in reinforcement frequencies. Amphetamine also increased responding, but higher doses of this drug produced marked hyperactivity and stereotyped movements which were not observed after idazoxan and yohimbine. Although the present behavioural baseline was not sensitive to antidepressants, it demonstrated an unexpected activity of two α2-adrenoceptor antagonists which deserves further investigation.
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  • 59
    ISSN: 1432-2072
    Keywords: Anhedonia ; Drive ; Extinction ; Free feeding ; Neuroleptic ; Pimozide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Both pimozide pretreatment and free feeding caused within-session and between-session decrements in variable interval operant performance; response decrements generated under pimozide were maintained on transfer to free feeding, and vice versa. On subsequently testing under extinction conditions (after food deprivation and drug free) large initial increases in responding were seen in all groups, and subsequent response decrements in extinction were steeper than in either pimozide or free feeding conditions. The effects of pimozide pretreatment do not resemble those of extinction, but may in some circumstances be functionally equivalent to a decrease in drive level.
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  • 60
    ISSN: 1432-2072
    Keywords: Nucleus accumbens ; d-Amphetamine activity ; Exploration ; Raclopride ; D2-receptors ; Schizophrenia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of the D2-antagonist raclopride was investigated in two test situations, which are presumed to involve dopamine (DA) transmission within the nucleus accumbens of the rat. Local injection of d-amphetamine sulphate (10 μg/0.5 μl) produced a marked increase in motor activity, measured as motility, locomotion, and rearing, which was dose- and time-dependently antagonised by local injection of raclopride (0.05–5.0 μg/0.5 μl). After an initial decrease, at low doses (0.05–0.25 μg/0.5 μl) an apparent enhancement of the d-amphetamine-induced motor activity appeared, which was most clearly seen with rearing. These lower doses, however, did not induce any clear changes in the exploratory activity in a novel environment (i.e., the second test situation). Only the higher doses used (1.0–5.0 μg/0.5 μl) decreased exploratory activity during the first 5–10 min, also measured as motility, locomotion, and rearing. These data are discussed with respect to the role of D2-receptors within the nucleus accumbens of rats in the motor activity induced by a novel environment and d-amphetamine. Overall, the data underline previous notions that raclopride is a potent antagonist of DA-mediated behaviour.
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  • 61
    ISSN: 1432-2072
    Keywords: Tolerance ; Opioids ; Reinforcement ; Place conditioning ; Morphine ; U-69593 ; d-Amphetamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The issue of whether tolerance develops to the motivational effects of opioids was addressed by use of an unbiased place preference conditioning procedure. Administration of the μ-opioid agonists morphine or fentanyl produced dose-related preferences for the drug-associated place in control rats. In contrast, the κ-opioid agonist, U-69593 produced conditioned place aversions. Non-contingent administration of morphine (5.0 mg/kg/12 h) for 4 days prior to conditioning resulted in tolerance to its reinforcing effects, and cross-tolerance to the effects of fentanyl. No cross-tolerance to the motivational effects of the psychostimulantd-amphetamine or the κ-opioid agonist U-69593 was observed. Chronic administration of U-69593 prior to conditioning produced tolerance to its aversive effects. This treatment did not, however, modify the reinforcement produced by morphine. These data demonstrate that tolerance develops to both the reinforcing and aversive properties of opioids and suggest that differential cross-tolerance may provide a useful method for determining the pharmacological basis underlying drug-induced motivational effects.
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  • 62
    ISSN: 1432-2072
    Keywords: Clonidine ; Locus coeruleus ; Intracerebral infusion ; Withdrawal ; Naloxone ; Morphine ; 3-Methoxy-4-hydroxyphenylglycol (MHPG) ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clonidine, an alpha-2-adrenergic agonist, suppresses signs of opiate withdrawal in animals and in man. Electrical or chemical stimulation of the nucleus locus coeruleus (LC) increases noradrenergic activity and brain concentration of the noradrenergic metabolite MHPG, and produces many signs of opiate withdrawal. Thus, clonidine's ability to attenuate withdrawal might be due to the reduction of noradrenergic neuronal activity originating in the LC, but additional alpha-2-adrenergic receptors throughout the body and other mechanisms may also play a role. The present study explored the neuroanatomical and pharmacological selectivity of alpha-2-adrenergic receptors of the LC in the anti-withdrawal action of clonidine. Experiment 1 tested the hypothesis that behavioral and biochemical measures of naloxone-precipitated withdrawal from morphine would be blocked by infusions of clonidine (0.6 or 2.4 μg/μl) into the LC. Significant reductions were observed in the occurrence of diarrhea, ptosis, weight loss and wet-dog shakes. Clonidine also reversed the naloxone-precipitated increase in hippocampus MHPG concentration. In experiment 2 subjects received an LC infusion or IP injection of a non-lipophilic alpha-2-agonist (ST-91), which does not penetrate the blood-brain barrier, or of clonidine into the dorsal parabrachial nucleus (DPB) to test the selectivity of the effects of clonidine infusions into the LC. ST-91 infusions into the LC reduced several of the observed withdrawal signs and increased others (e.g., jumping). Although peripheral injections of ST-91 attenuated some of the checked signs associated with naloxone-precipitated withdrawal, the frequency of wet-dog shakes was not reduced. ST-91 infusions into the LC, but not systemic ST-91 administration, prevented the withdrawal-induced increase in hippocampus MHPG concentration. Clonidine infused lateral to the LC into the DPB did not significantly attenuate withdrawal or reduce hippocampus MHPG levels. These results provide behavioral and biochemical evidence to support the suggestion that clonidine significantly attenuates naloxone-precipitated withdrawal through an interaction with noradrenergic neurons located in the vicinity of the LC.
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  • 63
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    Psychopharmacology 96 (1988), S. 135-141 
    ISSN: 1432-2072
    Keywords: Apomorphine ; Sulpiride ; SCH-23390 ; Central drug administration ; Dopamine autoreceptors ; Feeding behaviour ; Microstructural analysis ; Eating rate ; Eating time ; Open field ; Nucleus accumbens ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The inhibition of feeding following the administration of apomorphine, systemically or directly into the nucleus accumbens/ventral striatum, was studied using a microstructural analysis paradigm. On systemic administration, apomorphine reduced food consumption, eating rate and eating time; the effects were blocked by sulpiride but not by SCH-23390. Two doses of apomorphine were administered centrally. Both doses reduced total food intake and eating rate; only the higher dose also reduced eating time; all of these effects were blocked by sulpiride pretreatment. Only the lower dose reduced locomotor activity and rearing in the open field. The results suggest that apomorphine reduces eating rate by an action on dopamine (DA) axon terminal autoreceptors. We have previously demonstrated that apomorphine reduces eating time by an action on DA cell body autoreceptors. Therefore, the two populations of DA autoreceptors appear to be differentially involved in behaviour.
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  • 64
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    Psychopharmacology 95 (1988), S. 195-199 
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Scopolamine cue ; Muscarinic agonists ; Muscarinic antagonists ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The discriminative stimulus properties of scopolamine, a potent antagonist at muscarinic receptors, were used for testing the discriminative effects of drugs known to act on cholinergic transmission. Rats were trained in a standard two-bar operant conditioning procedure with food as the reinforcer, according to a FR10 schedule. The training dose of scopolamine was progressively reduced from 0.25 mg/kg SC to the low dose of 0.062 mg/kg SC. Scopolarmine yielded an accurate discrimination in all the six rats tested. The generalization gradient resulted in an ED50 of 0.027 mg/kg. The scopolamine cue lasted for 1 h and was of central origin, since it was not mimicked by scopolamine methylbromide. The scopolamine stimulus generalized to atropine and trihexyphenidyl (respective ED50 values 2.20 and 0.21 mg/kg SC). Atropine depressed rate of responding, while trihexyphenidyl did not. Antagonism experiments with both direct agonists at the muscarinic receptor (arecoline and oxotremorine) and indirect agonists, i.e., inhibitors of the acetylcholine esterase [physostigmine and tetrahydroaminoacridine (THA)], led to inconsistent results. Increasing the doses of the agonists in order to block the scopolamine cue may be limited by their rate suppressant effect on responding. Based upon previously published results, it is suggested that the muscarinic agonist cue is more useful than the antagonist cue for investigating muscarinic transmission.
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  • 65
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Cocaine ; Tolerance ; CNS stimulants ; Rat ; Amphetamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to discriminate cocaine, 10.0 mg/kg, using a two-lever operant procedure. Dose-effect data were determined for the substitution of cocaine, diethylpropion, methylphenidate, phenmetrazine, phentermine, and fenfluramine for the cocaine stimulus. All of these drugs, except fenfluramine, substituted fully for the cocaine stimulus. Subsequently, training was halted and cocaine, 20 mg/kg/8 h, was administered for 9 days, and dose-effect data were redetermined for all of these drugs on days 7–9 of chronic administration. Chronic administration of cocaine produced tolerance to the stimulus properties of cocaine, and cross-tolerance to the stimulus properties of methylphenidate, phenmetrazine, and phentermine, such that doses approximately two-fold higher than those used acutely were necessary to reproduce the original effect; the potency for the substitution of diethylpropion for the cocaine stimulus was decreased greater than four-fold; and fenfluramine still failed to substitute for the cocaine stimulus. These data suggest that 1) a common mechanism may mediate tolerance to the discriminative stimulus properties of cocaine, methylphenidate, phenmetrazine, and phentermine, and 2) tolerance in the drug discrimination procedure may have potential for establishing a comprehensive evaluation of dependence liability of CNS stimulants.
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  • 66
    ISSN: 1432-2072
    Keywords: Tachykinins ; Senktide ; Cholinergic ; Autoreceptor ; 6-Hydroxydopamine ; Yawning ; Mouth movements ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The selective NK-3 tachykinin receptor agonist senktide elicited yawning, chewing mouth movements and sexual arousal following subcutaneous administration (0.1–1.0 mg/kg) in the rat. These responses were not significantly affected by the dopamine antagonist haloperidol (0.03 mg/kg) or by 6-hydroxydopamine lesions of the nigrostriatal projection. In contrast, the behaviours were markedly attenuated by the peripheral and central muscarinic antagonist scopolamine (1 mg/kg), but not by the peripheral muscarinic antagonist N-methylscopolamine (1 mg/kg). These findings suggest that stimulation of NK-3 receptors produces yawning, chewing and sexual arousal by directly activating central cholinergic neurons.
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  • 67
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    Psychopharmacology 96 (1988), S. 262-266 
    ISSN: 1432-2072
    Keywords: Alpha-melanotropin ; Inulin ; Blood-brain barrier ; Lipid solubility ; Pharmacokinetics ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The permeability of the blood-brain barrier (BBB) to immunoreactive alpha-melanotropin (α-MSH) was quantified in rats pretreated with monosodium l-glutamic acid to deplete their CNS stores of endogenous α-MSH. The methodology, suitable for poorly permeable substances, monitored blood and brain tissue concentrations of α-MSH over 15 min following intravenous injection of 30 nmol synthetic α-MSH. Rate constants for entry of α-MSH into brain tissue were estimated from separate nonlinear least-squares fits of connecting two- and one-compartment open models to plasma and extravascular brain tissue concentration data, respectively. Comparisons were made to rate constants measured similarly for 14C-inulin. The BBB had a low permeability to immunoreactive α-MSH, consistent with peptide penetrating the barrier by passive diffusion dependent upon the lipid solubility of the molecule.
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  • 68
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    Psychopharmacology 96 (1988), S. 281-284 
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Oral administration ; Transdermal administration ; Nicotine ; Cytisine ; Arecoline ; Mecamylamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a standard two-lever drug discrimination paradigm, rats were trained to discriminate nicotine 0.5 mg/kg PO from saline. Injections occurred 15 min before the session. Subjects reached the training criterion in a mean of 38 sessions. Nicotine PO, SC, and IP generated similar dose-effect curves (ED50=0.073 mg/kg PO, 0.076 mg/kg SC, 0.090 mg/kg IP); the dose-effect curve for transdermal (TD) administration fell approximately 1 log unit to the right (ED50=1.34 mg/kg). The percentage of rats choosing the nicotine-appropriate lever peaked at 15 min and gradually decreased to 50% or less by 180 min for nicotine PO and TD, a time-decay function similar to that previously shown for SC administration. The nicotinic cholinergic agonist cytisine (0.5–8.0 mg/kg) PO and TD produced up to 56% nicotine-appropriate responding, while the muscarinic cholinergic agonist arecoline (1.0–4.0 mg/kg) PO and TD produced only saline-appropriate responding. The nicotine cue did not generalize to the cholinergic antagonist mecamylamine (0.125–0.5 mg/kg) PO or TD; mecamylamine 0.5 mg/kg PO but not TD completely blocked the PO and TD nicotine cues. These results show that an approximately equal cue occurs with PO, IP, and SC administration, and that the TD cue is considerably weaker. The significance of the procedure as an animal analog of human transdermal nicotine intake is discussed.
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  • 69
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    Psychopharmacology 96 (1988), S. 311-316 
    ISSN: 1432-2072
    Keywords: Rat ; Neuroleptics ; Catalepsy ; Dopamine receptors ; Muscarinic receptors ; SCH23390 ; Pilocarpine ; Atropine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In an attempt to understand the nature of the interactions between D1 and D2 dopamine subsystems as well as between dopamine and acetylcholine, catalepsy was assessed in rats following various drug treatments. The D1-specific antagonist SCH23390 (0.1 mg/kg) produced prompt, potent and brief (〈90 min) catalepsy with an ED50 of 0.105 mg (0.3 μmol)/kg. Conversely, fluphenazine (0.1 mg/kg), spiroperidol (0.1 mg/kg), and haloperidol (0.2 mg/kg) all had comparably potent but more slowly rising and prolonged (〉240 min) effects. The action of SCH23390 was synergistic with spiroperidol, inhibited by apomorphine or atropine, unaffected by mecamylamine, and markedly potentiated by pilocarpine. However, pilocarpine was unable to significantly potentiate the action of fluphenazine or spiroperidol. It is inferred that SCH23390 differs from the classical neuroleptics in its mechanism of cataleptogenicity, that there is a cholinergic link with the D1 dopamine system, and further, that there may be a difference in the nature or impact of the cholinergic interaction with the D1 and D2 dopamine systems.
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  • 70
    ISSN: 1432-2072
    Keywords: Nicotine ; Ageing ; Body weight ; Water intake ; Locomotor activity ; Exploratory behavior ; Memory ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To assess the effects of long-term treatment with nicotine on several behavioral measures (locomotor activity, exploratory efficiency, habituation, short-term and long-term memory) of young (5 months) and old (22 months) rats in a hexagonal tunnel maze, nicotine was added to the drinking water (0, 20 or 50 mg/l) for up to 131 experimental days. With the exception of effects on exploratory efficiency, young and old rats did not differ in their response to the drug. Nicotine decreased body weight throughout the experiment. Nicotine treatment reduced water intake during the first 30 min of the daily 4.5 h access to drinking water. Nicotine increased locomotor activity throughout the experiment. When nicotine treatment was discontinued during a 7-day withdrawal period, locomotor activity immediately dropped to control values. Intertrial habituation was not affected by nicotine. Long-term nicotine treatment had an attenuating effect on exploratory efficiency in young rats; however, the drug did not influence performance in tasks measuring spatial memory. Finally, age increased weight, decreased locomotor activity and impaired exploratory efficiency and short-term memory. Age, however, did not affect the performance of the long-term memory task.
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  • 71
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    Psychopharmacology 94 (1988), S. 119-125 
    ISSN: 1432-2072
    Keywords: Place conditioning ; Cocaine ; Intraperitoneal and intravenous administration ; Reward ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been shown that pretreatment with dopamine (DA) receptor blockers disrupts the effect of intravenously (IV) and intracerebrally (ICV), but not intraperitoneally (IP) administered cocaine on place preference conditioning (PPC). The present study was undertaken to further evaluate possible differences between IV and IP cocaine PPC. To this end, several factors which may differentially influence IV and IP cocaine PPC were examined. Firstly, dose-response effects were studied. Intravenous cocaine produced PPC within a narrow dose range (0.5–2.5 mg/kg). Animals receiving IV injections of 5 and 10 mg/kg cocaine experienced convulsions and did not show PPC. For IP cocaine a 10-fold increase in dose (10 mg/kg) and twice the number of training trials was required in order to obtain PPC equal in magnitude to that with IV cocaine (0.5 mg/kg; two trials). Cocaine PPC was retained at least 1 month. Following IV cocaine preference developed for the side associated with the drug regardless of whether the conditioning was to the least or most preferred side. After IP cocaine, preference developed for the drug side only when the drug was paired with the least preferred side. Rats trained with IV, but not IP, cocaine significantly preferred the drug familiar side to a novel compartment. Preference for the IV or IP cocaine side developed regardless of whether testing was carried out in the drugged or undrugged state, excluding possible state-dependent effects as an explanation of the cocaine PPC. The results show PPC procedure to be a valid test for evaluating rewarding properties of IV cocaine. However, they fail to show rewarding effects of IP cocaine.
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  • 72
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    Psychopharmacology 94 (1988), S. 133-137 
    ISSN: 1432-2072
    Keywords: Diazepam ; Haloperidol ; Domperidone ; 6-Hydroxydopamine ; DSP-4 ; Place conditioning ; Dopamine ; Noradrenaline ; Reward ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The conditioned place preference paradigm was used to investigate the neurochemical and neuroanatomical substrates which mediate the rewarding properties of diazepam. The results confirmed that diazepam (1 and 2.5 mg/kg, IP) produced place preference for a distinctive environment that had previously been paired with injections of the drug. Pretreatment with haloperidol (0.1 mg/kg) antagonised the place preference induced by diazepam (1 mg/kg). Pretreatment with domperidone (2 mg/kg) failed to influence this effect of diazepam. Haloperidol (0.1 mg/kg) and domperidone (2 mg/kg) alone did not produce place aversion. In separate experiments the diazepam-induced place preference was examined in rats having 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens. These animals did not show preference for the compartment associated with diazepam. Depletion of central noradrenaline produced by systemic injections of DSP4 did not affect diazepam-induced place preference conditioning. These findings suggest that dopamine-containing neurons of the mesolimbic system are a component of the neural circuitry that mediates the reinforcing properties of diazepam.
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  • 73
    ISSN: 1432-2072
    Keywords: Electroconvulsive shock ; 5-HT transporter complex ; β-Adrenoceptor ; [3H]-Paroxetine ; [3H]-Imipramine ; [3H]-Dihydroalprenolol ; Cerebral cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of repeated electroconvulsive shock on the 5-HT uptake site were studied in rat cortex using [3H]-paroxetine binding. This ligand was used because it is thought to directly label the 5-HT uptake site, whereas [3H]-imipramine may bind to a presynaptic recognition site different from the uptake site. No changes were found in the maximum number of [3H]-paroxetine binding sites and equilibrium dissociation constant after repeated electroconvulsive shock, whereas a parallel investigation of β-adrenoceptor binding showed the expected decrease in receptor number.
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  • 74
    ISSN: 1432-2072
    Keywords: Benzodiazepines ; Triazolopyridazines ; Noradrenaline ; Clonidine ; Yohimbine ; Drug discrimination stimulus ; Fixed ratio performance ; Bicuculline ; Ro 15-1788 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of clonidine on the antianxiety and sedation of benzodiazepines (BZD) were assessed respectively in rats trained in a two-lever diazepam cue discrimination procedure and in single-lever fixed-ratio (FR) water-reinforced performance. Clonidine (10–60 μg/kg) significantly shifted to the left the dose-effect curves of diazepam in the discrimination paradigm. This treatment also shifted generalization dose-effect curves of the diazepam cue to chlordiazepoxide and CL 218872 to the left in the drug discrimination procedure. The diazepam cue was antagonized in a dose-related manner by Ro 15-1788, but not by bicuculline. Clonidine also potentiated the rate-decreasing effects of diazepam on the FR schedule when the dose of diazepam was increased to 0.3 mg/kg, but not the milder rate-decreasing effect of CL 218872 until the dose of CL 218872 was increased to 10 mg/kg. The potentiating effects of clonidine on the stimulus control and depression of diazepam were antagonized by yohimbine. Yohimbine (1.0 mg/kg) also significantly shifted the dose-effect curve of diazepam cue to the right. Bicuculline (3 mg/kg) completely antagonized the rate-decreasing effect of diazepam (1 mg/kg), but significantly potentiated the rate-suppressant effect of clonidine (10 μg/kg). These results suggest that the central noradrenaline (NA) system may be involved not only in the antianxiety, but also the sadative action of BZD. The nature of NA involvement in relation to the different subtypes of BZD receptors requires further exploration.
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  • 75
    ISSN: 1432-2072
    Keywords: LY 171555 ; SKF 38393 ; Combined D1 and D2 stimulation ; SCH 23390 ; D1 supersensitivity ; Locomotor activity ; Grooming ; Stereotyped behaviour ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The selective D1 receptor stimulant SKF 38393 dose-dependently increased grooming time in rats without affecting locomotor activity or eliciting stereotyped behaviour. The selective D2 receptor agonist LY 171555 induced a dose-dependent increase in rat motility, a marked decrease in grooming time and a low occurrence of stereotyped behaviour. Concurrent administration of the two selective agonists induced high-degree stereotyped responses and reductions in locomotor and grooming behaviours. Rats withdrawn from repeated treatment with the selective D1 receptor blocker SCH 23390 (0.05 mg/kg twice daily for 21 days; 7 days of washout) did not exhibit any change of locomotor and grooming responses to threshold doses of LY 171555 and SKF 38393 given alone or in combination. On the contrary, a significantly greater occurrence of high-degree stereotyped responses to the combination of the two selective agonists was observed. The data support the view that D1 and D2 receptors have a cooperative role in the generation of stereotypies and suggest that D1 receptor supersensitivity needs D2 stimulation to be revealed.
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  • 76
    ISSN: 1432-2072
    Keywords: Amphetamine ; Circling behavior ; Asymmetry ; Pavlovian conditioning ; Sensitization ; Placebo ; Latent inhibition ; Extinction ; Reverse tolerance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Amphetamine-induced circling behavior increases over the course of repeated administration of the drug; likewise, after repeated administration of amphetamine, an injection of saline prior to placement of the rat in the test apparatus previously associated with the pharmacologic effects of amphetamine will increase circling behavior. Experiments were designed to determine if either of these effects would respond to manipulation of the temporal contiguity between the test environment and the peak effects of amphetamine. The placebo-like response, in accordance with a Pavlovian conditioned response, was reduced by prior non-reinforced exposure to the test environment and subject to extinction. In contrast, the increase in the amphetamine-induced response was entirely dependent on the test environment but not affected by latent inhibition or extinction. These and previous findings indicate that the development and expression of the placebo-like response is the result of a Pavlovian associative process. Although amphetamine sensitization is environment dependent, it does not resemble a conditioned response in other respects.
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  • 77
    ISSN: 1432-2072
    Keywords: Haloperidol ; Partial reinforcement ; Continuous reinforcement ; Extinction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of haloperidol 0.1 mg/kg on the partial reinforcement extinction effect (PREE) paradigm at one trial a day, were examined. Two groups of rats were trained to run in a straight alley. The continuously reinforced (CRF) group received food reward on every trial. The partially reinforced (PRF) group was rewarded on a quasirandom 50% schedule. All animals were then tested in extinction. Haloperidol 0.1 mg/kg was administered in a 2 × 2 design, i.e., drug-no drug in acquisition and drug-no drug in extinction. The PREE, i.e., increased resistance to extinction of partially reinforced as compared to continuously reinforced animals, was obtained in all four drug conditions. The administration of haloperidol in acquisition increased markedly resistance to extinction in CRF animals. The administration of the drug in extinction decreased resistance to extinction in both CRF and PRF animals. The results are explained in terms of two independent actions of haloperidol: the well-known effect of reduction in the effectiveness of reinforcement as well as enhancement of the effectiveness of nonreinforcement.
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  • 78
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    Psychopharmacology 96 (1988), S. 40-44 
    ISSN: 1432-2072
    Keywords: Drug discrimination ; d-Amphetamine ; Nimodipine ; Diazepam ; Morphine ; Haloperidol ; Calcium channel ; Behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The discriminative stimulus (DS) properties ofd-amphetamine (AMP) are thought to be mediated by enhanced release of catecholamines, which may involve neuronal calcium influx through voltage sensitive channels. The present study examined the influence of nimodipine, a calcium channel blocker, on the DS properties of AMP. Rats (N=8) were trained to discriminate AMP (0.5 mg/kg, IP) from saline in a two-lever, food-reinforced, drug discrimination paradigm. Nimodipine alone (2.0–5.6 mg/kg, IP) did not substitute for AMP. When given in combination with AMP, 2.0 mg/kg nimodipine increased by less than 2-fold the AMP dose necessary to induce AMP-appropriate responses. Higher doses of nimodipine combined with AMP did not increase the magnitude of this effect. Nimodipine enhanced the effects of AMP on response rate. Haloperidol (0.125 mg/kg) increased by approximately 4-fold, whereas diazepam (0.5 or 1.0 mg/kg) and morphine (5.0 mg/kg) increased by approximately 2-fold the AMP dose necessary to induce AMP-appropriate responses. The interaction with AMP was associated with enhanced reduction of response rate in the tests with diazepam and morphine but not haloperidol. These results suggest that nimodipine attenuates the DS properties of AMP, probably in a non-specific way, due to the ability of nimodipine itself to induce a discriminable internal state.
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  • 79
    ISSN: 1432-2072
    Keywords: Rat ; Drug discrimination ; NMDA ; Phencyelidine ; ±SKF 10047 ; MK 801 ; CPP ; Ifenprodil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to discriminate phencyclidine (PCP) from saline at doses of 2 and 4 mg/kg, using a two-lever food reinforced operant technique. ±N-allylnormetazocine (±SKF 10047), +5-methyl-10,11-dihydro-5H-dibenzo[A,D]cyclohepten-5,10-imine (MK 801), 3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP) and ifenprodil, which have been shown to antagonise the effects of N-methyl-d-aspartate (NMDA), were tested for their ability to give rise to PCP-appropriate responding. In rats trained at both doses of PCP, ±SKF 10047 (2–12 mg/kg) and MK 801 (0.0125–0.2 mg/kg) produced dose-related responding on the lever associated with PCP injection. The relative potency of these two compounds was the same in the two groups of animals, but their absolute potencies to produce a PCP-like discriminative stimulus were dependent on the training dose of PCP. In contrast, neither the competitive NMDA antagonist CPP (4–20 mg/kg) nor the non-competitive antagonist ifenprodil (2–12 mg/kg) produced PCP-appropriate responding and ifenprodil (4-mg/kg) neither potentiated nor antagonised PCP. These findings are discussed in the light of the hypothesis that the behavioural effects of PCP are mediated via a reduction of neurotransmission at the NMDA-subtype of glutamate receptors.
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  • 80
    ISSN: 1432-2072
    Keywords: Enkephalin ; Ventral mesencephalon ; Investigatory behaviour ; Motor behaviour ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mesolimbic dopamine (DA) system, originating in the ventral tegmental area and projecting to limbic forebrain regions, plays a crucial role in mediating several important aspects of behaviour. Proximal to these DA neurons are enkephalin-containing nerve fibers. In an attempt to characterize the behavioural role of enkephalinergic transmission in the VTA, the present experiment examined in detail the investigatory and motor responses to microinfusion of d-ala-met-enkephalin (DALA), a long lasting analogue of enkephalin, into the ventral tegmental area (VTA). Injections into the substantia nigra (SN) and the hippocampus (HPC) were also performed as controls for site specificity. The behavioural apparatus consisted of an eight-hole box monitored by a video camera. Four doses of DALA were injected in the VTA (0.05, 0.1, 1 and 2.5 μg/μl bilaterally in 1 μl volume) and one dose in the SN and HPC (0.1 μg/μl bilaterally in 1 μl volume). The effect of DALA injections in the VTA was characterized by an inverted U-shape dose-effect curve. The low doses (0.05 and 0.1) induced an increase in the frequency of hole visits accompanied by a decrease in the mean duration of visits, whereas the highest doses induced a decrease in hole visit frequency. Low doses of DALA had no effect on strategy or organization of exploration, whereas the high doses produced decreased switching between holes. After low doses of DALA, locomotor activity at the periphery of the testing box was not significantly affected but locomotor activity in the centre was increased. After high doses of DALA, locomotor activity in the center and at the periphery of the box were decreased. Frequency of rearing was either not affected or decreased by DALA treatment. DALA injected in the SN resulted in a small increase in frequency of hole visits and did not affect rearing and locomotor activity. DALA injection in the HPC had no effect on investigatory and spontaneous motor behaviour. The results are discussed in terms of a modulatory role of endogenous enkephalin on mesolimbic dopamine neurons.
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  • 81
    ISSN: 1432-2072
    Keywords: Alcohol drinking ; Brain amines ; Neonatal ; Open field ; Porsolt's swim test ; Propranolol ; Rat ; Sleep ; Spontaneous alternation ; Startle reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study examined the effects of early postnatal treatment with a beta-adrenoceptor antagonist propranolol (5 mg/kg IP daily) on concomitant and subsequent behavior and central aminergic transmission in rats. During propranolol exposure from the 7th to the 20th postnatal days sleep-wake recordings, carried out with the static charge sensitive bed (SCSB) method, showed a decrease in the percentage of active sleep and an increase in waking. When the animals were 1–3 months of age, the open field behavior was changed, immobility time in the Porsolt's swim test was lengthened, and voluntary alcohol consumption was increased in the propranolol-treated rats. Neither motor reactivity to auditory stimuli nor spontaneous alternation behavior was affected. At the age of 4 months concentrations of brain amines and their metabolites were measured from several brain regions. In the propranolol-treated rats the noradrenaline levels were increased in the limbic forebrain and cerebellum. The results suggest that in rats the exposure to propranolol during the rapid growth period of cerebral catecholamine systems, and the concomitant alterations in sleep are related to later changes in behavior and to increased noradrenaline content in the limbic forebrain and cerebellum.
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  • 82
    ISSN: 1432-2072
    Keywords: Noradrenaline ; DSP4 ; Operant behaviour ; Herrnstein's equation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of the selective noradrenaline neurotoxin DSP4 on steady-state operant behaviour was examined using a quantitative behavioural paradigm based on Herrnstein's (1970) equation, which defines a hyperbolic relationship between steady-state response rate and reinforcement frequency in variable-interval schedules. Eleven rats received injections of DSP4 (two doses of 50 mg/kg, intraperitoneally), and 12 rats received injections of the vehicle alone. The rats were trained to steady state in a series of six variable-interval schedules of sucrose reinforcement, affording scheduled reinforcement frequencies of 4–360 reinforcers per hour. Herrnstein's equation was fitted to the data obtained from each rat and to the averaged data obtained from the two groups. The value ofK H (the parameter expressing the reinforcement frequency needed to maintain the half-maximal response rate) was higher in the DSP4-treated rats than in the control rats; the value ofR max (the parameter expressing the maximum response rate) did not differ significantly between the two groups. At the end of the behavioural experiment the rats were sacrificed for determination of the concentrations of catecholamines in the brain by high-performance liquid chromatography. The levels of noradrenaline in the parietal cortex, hippocampus and cerebellum of the DSP4-treated rats were less than 20% of those of the control rats. The results provide further evidence that central noradrenergic neurones are involved in the maintenance of operant behaviour by positive reinforcement.
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  • 83
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    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 463-471 
    ISSN: 1432-1912
    Keywords: 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] ; 5-HT1A receptors ; CNS ; 5-HT synthesis and release ; Hemitransection ; Dorsal raphé application ; Regulation of 5-HT activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study was undertaken in an attempt to assess whether the effects of the potent and selective 5HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT, on cerebral 5-hydroxytryptamine (5-HT) neurochemistry in vivo are mediated via 5-HT autoreceptors on the cell bodies or on the terminals, and/or via postsynaptic 5-HT receptors. To this end we determined in vivo indices of 5-HT synthesis and release/turnover rates in a number of prominent 5-HT neuronal projection areas in the CNS i) after systemic administration of 8-OH-DPAT to rats with an acute unilateral axotomy of the ascending mesencephalic monoamine neurones, or ii) after local infusion of the compound into the dorsal raphé (DRN) 5-HT cell body region of intact rats. Transection did not alter 5-HT synthesis per se, but prevented the synthesis-inhibitory effect of 8-OH-DPAT. Thus, the 5-HT synthesis-inhibiting action of 8-OH-DPAT is highly dependent upon intact impulse flow in the central 5-HT neurones. On the other hand, local DRN application of the compound (1 μg) resulted in a clearcut reduction of the 5-HT synthesis and release indices measured in 5-HT terminals in, e. g., the striatum. These findings provide direct neurochemical evidence that by preferentially stimulating somatodendritic 5-HT1A receptors, 8-OH-DPAT inhibits the 5-HT neuronal impulse flow, thereby effectuating decreased terminal 5-HT synthesis and release. Taken together, the data are consistent with the suggestion that 8-OH-DPAT acts as an agonist preferentially at cell body vs. terminal 5-HT autoreceptors, therefore also emphasizing the distinction between terminal and cell body 5-HT autoreceptors. The results obtained may have important implications for the understanding of mechanisms involved in regulating the activity of central serotoninergic neurones.
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  • 84
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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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  • 85
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    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 96-98 
    ISSN: 1432-1912
    Keywords: Histamine ; Gastric acid secretion ; Central nervous system ; Vagus nerve ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Administration of 10–100 μg of histamine into the lateral cerebral ventricle of anaesthetized rats stimulated gastric acid secretion in a dose-dependent manner, while subcutaneous (s. c.) injections of the same doses produced clearly less pronounced increases in the acid output. In vagotomized rats only a marginal response to histamine given into the lateral ventricle was observed. When injected into the third cerebral ventricle the doses of histamine needed for the stimulation of gastric acid secretion were 1–10 μg, the effect being totally abolished by vagotomy. The results indicate that histamine is capable of stimulating gastric acid secretion by a central, vagal-dependent mechanism.
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  • 86
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    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 345-349 
    ISSN: 1432-1912
    Keywords: 5-HT ; Tryptophan hydroxylase ; Sex difference ; Brain ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies have revealed that brain levels of tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) are moderately higher in female than in male rats. Since tryptophan hydroxylase is only about half saturated with substrate, the greater availability of precursor in female rats might contribute to their higher 5-hydroxyindole levels. The present investigation was aimed at clarifying whether there is a sex difference in central tryptophan hydroxylase capacity. Hence, both sexes received a high dose of l-tryptophan (400 mg/kg), which resulted in a tenfold increase in brain tryptophan concentrations and presumably a virtual saturation of tryptophan hydroxylase. Following such treatment, 5-hydroxytryptophan (5-HTP) levels, measured after l-amino acid decarboxylase inhibition, were compared in males and females. Both in saline-and l-tryptophan-treated rats, 5-HTP levels were generally higher in females. In another group of animals, receiving 400 mg/kg of l-tryptophan as sole treatment, 5-HT and 5-HIAA concentrations were measured. As in the case of 5-HTP, the higher 5-HT and 5-HIAA levels observed in females persisted after l-tryptophan treatment. The present data suggest that brain tryptophan hydroxylase activity is greater in females; this sex difference probably contributes to the higher 5-HT and 5-HIAA levels in females.
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  • 87
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    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 287-292 
    ISSN: 1432-1912
    Keywords: PYY ; Rat ; Non-adrenergic ; Non-cholinergic ; In vitro ; Small intestine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of peptide YY (PYY) on motor activity of the rat small intestine, were studied using isolated organ bath preparations arranged for recording muscle activity in the longitudinal axis. PYY induced TTX sensitive concentration-dependent contractions and/or relaxations of the longitudinal muscle in different regions of the small intestine. In the duodenum PYY evoked only “cholinergic” contractions (3 × 10−8−3 × 10−7 M). In the jejunum, PYY-evoked concentrations were non-cholinergic, and contractions were never seen in the ileum. In the jejunum and ileum, PYY-evoked relaxations (3 × 10−3 × 10−7 M) were unaffected by adrenoceptor or cholinergic receptor blockade, thus indicating that these relaxations were mediated by non-adrenergic, non-cholinergic (NANC) inhibitory nerves. Another action of PYY was to cause inhibition of field stimulation-evoked cholinergic concentrations. This inhibitory action was primarily due to antagonism of post-junctional, cholinergic receptor mediated events. In addition, PYY inhibited histamine evoked contractions of the longitudinal muscle. All regions of the small intestine could be desensitized to PYY. Such PYY-densensitization did not affect the ability of the longitudinal muscle to relax in response to applied ATP or papaverine. These results suggest PYY has potent concentration-dependent stimulatory actions at intrinsic inhibitory and excitatory motor nerves. In addition, PYY interferes with contractions but not relaxations of the longitudinal muscle.
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  • 88
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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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  • 89
    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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  • 90
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    Experimental brain research 71 (1988), S. 611-617 
    ISSN: 1432-1106
    Keywords: Retina ; Projection ; Development ; Rat ; Rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We traced the retino-retinal projection with Rhodamine B isothiocyanate (RITC), Rhodamin labelled latex microspheres (RLM), horseradish peroxidase (HRP) and choleratoxin conjugated horseradish peroxidase (BHRP). The number and distribution of ganglion cells projecting to the contralateral eye were recorded. Newborn and young rats have up to about 130 ganglion cells projecting to the other retina; this confirms previous findings. We extended these findings in two ways. First, we describe a similar projection in rabbits consisting of fewer cells; second, we describe the persistence of a small component of this projection into adulthood. In addition we show with RITC and Nuclear Yellow double tracing that some of the retino-retinal ganglion cells have an axon collateral which projects to the superior colliculus. We performed control experiments in order to exclude spillover of tracer which might produce false positive labelling.
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  • 91
    ISSN: 1432-1106
    Keywords: Galanin ; Spinal cord ; Flexor reflex ; Intrathecal ; Cutaneous afferents ; Thermoreceptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The neuropeptide galanin (GAL) was injected intrathecally (i.t.) in decerebrate, spinalized, unanesthetized rats and its effect on the nocifensive flexor reflex was examined. The reflex, which was evoked by intense mechanical or thermal stimulation of the foot, was recorded from the ipsilateral hamstring muscles. I.t. GAL increased reflex excitability significantly more to thermal than to mechanical stimuli. It is suggested that GAL, which is present in sensory fibers that innervate the skin, is released by the central terminals of cutaneous afferents that are much more sensitive to thermal than to mechanical stimuli.
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  • 92
    ISSN: 1432-1106
    Keywords: Hypoglossal nucleus ; Biogenic amines ; Immunocytochemistry ; Tyrosine hydroxylase ; Serotonin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of biogenic amines in the rat hypoglossal nucleus (nXII) was investigated with immunocytochemical methods using antibodies to tyrosine hydroxylase (TH) as a marker for catecholamines, and to 5-hydroxytryptamine (5-HT), the principal indoleamine, at the light microscopic level. TH and 5-HT immunoreactivity were found throughout all regions of nXII. Although the innervations overlapped, clearly differnt patterns of distribution were observed. TH immunoreactivity was localized primarily in the ventromedial quadrant of the caudal half of nXII and appeared largely as perisomatic-like profiles. In contrast, 5-HT immunoreactivity was greatest dorsally along the caudal half of nXII, although secondary foci of staining were evident ventrolaterally and, to a lesser extent, ventromedially. A perisomatic-like pattern of termination was observed for 5-HT in both dorsal and ventral regions of nXII. Since ventral and dorsal districts of nXII contain motoneurons that innervate protrusor and retrusor tongue muscles, respectively, we propose that the overlapping, yet differential distributions of catecholamines and indoleamines are important in controlling the relationships between functionally related groups of nXII motoneurons. These findings are discussed in relation to oro-lingual motor dysfunction.
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  • 93
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    Experimental brain research 73 (1988), S. 393-401 
    ISSN: 1432-1106
    Keywords: Rat ; Ganglion cell axons ; Regeneration ; Chemically defined media ; Fluorescent tracers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The potential for regeneration of adult rat ganglion cell (RGC) axons was investigated in vitro. Explants from RITC (rhodamine-B-isothiocyanate) retrogradely labeled and in vivo axotomized retinae were placed on dishes coated with various substrates. The retinal pieces were cultivated in a serum-free medium and incubated under 50 to 80% O2-enriched and 5% CO2-containing atmosphere. Under these conditions, massive outgrowth of fibers was observed as early as 24 h after explantation and over a period of time extending up to 7 days in culture. By various criteria, two main types of processes could be characterized: (1) Short, thick processes emerged from either migrated flat cells or from cells inside the retinal explant, and (2) long and thin processes emerged from cells in the ganglion cell layer (GCL). By immunohistochemistry, the short processes and the cells from which they had emerged, appeared to be glial acidic fibrillary protein (GFAP)-positive Thy 1 and L 1-negative, suggesting their glial nature. The second type of long, thin processes appeared to be GFAP-negative, L1- and Thy 1-positive, indicating that they were neuronal, probably RGC processes. Proof that long fibers emerged from RGCs was provided by retrograde labeling of RGCs with RITC prior to explanation. Numerous RITC-filled RGCs survived in vitro. Regrowing axons retransported part of the accumulated fluorescent dye in the orthograde direction and thus unequivocally permitted their identification as RGC axons. The fact that adult RGC axons can reelongate in vitro might provide a useful bioassay for investigations on the factors that either support or inhibit regrowth of axons from CNS neurons.
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  • 94
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    Experimental brain research 69 (1988), S. 417-423 
    ISSN: 1432-1106
    Keywords: Nucleus reticularis tegmenti pontis ; Vestibular ; Flocculus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Forty-nine neurons were recorded in the nucleus reticularis tegmenti pontis (NRTP) during horizontal vestibular and/or optokinetic stimulation in immobilized pigmented rats. During optokinetic stimulation, the response of NRTP neurons was either unidirectional (51%) or bidirectional (49%). Histological reconstruction showed that unidirectional neurons were located in the dorsal-medial part of NRTP, and bidirectional neurons in the lateral part. All neurons exhibited a response during pure vestibular sinusoidal stimulation in the frequency range 0.025 Hz-0.2 Hz. NRTP neurons were divided into two groups according to their threshold to vestibular stimulation. Group A neurons had a low threshold, a low spontaneous activity and their firing frequency slowly increased with acceleration. Group B neurons showed opposite characteristics. Phase and gain analysis suggested that NRTP neurons carry a head velocity signal. After hemiflocculectomy, the gain of the vestibular response of contralateral NRTP neurons increased. From these data, the role of NRTP in the horizontal vestibulo-oculomotor is discussed.
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  • 95
    ISSN: 1432-1106
    Keywords: AP5 ; NMDA antagonist ; Hippocampus ; DRL ; Memory ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats were trained to lever press on a differential reinforcement of low rates (DRL-18 s) schedule. They were then allocated to four treatment groups. These were: hippocampal aspiration lesions [HIPP]; implantation of osmotic minipumps for intraventricular infusion of either (a) the NMDA receptor antagonist 30 mM D, L-2-amino-5-phosphonopentanoic acid [AP5] or (b) vehicle [VEH]; and an unoperated control group [UNOP]. In subsequent DRL testing, the HIPP group showed a profound and enduring loss of efficiency, resulting from an increased tendency to respond too early; the AP5 group showed a qualitatively similar, but less severe, impairment followed by full recovery once the minipumps had expired; the VEH and UNOP groups both maintained their pre-operative levels of efficiency. We conclude that AP5 infusion disrupts temporary memory storage in the hippocampus, and that the hippocampus is concerned with the retention of memories outside the purely spatial domain.
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  • 96
    ISSN: 1432-1106
    Keywords: Dorsal lateral geniculate nucleus ; Horseradish peroxidase ; Retinal axons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Retinal endings in the dorsal lateral geniculate nucleus (dLGN) of the rat were visualized by anterogradely transported horseradish peroxidase following injections in the optic tract. The morphological findings confirm the two types of retinal axons previously suggested by Golgi investigations. In the caudal third of the dLGN type 2b axons, with small dense clusters of boutons, are the only representatives of retinal fibres seen. In the rostral two thirds they are intermingled with the larger type 2a terminals, but tend to accumulate laterally, adjacent to the optic tract. This study supports the concept that large retinal ganglion cells probably give rise to 2a axons that may represent a Y-like channel, whereas 2b axons are derived from small ganglion cells, and may relay a W-like pathway.
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  • 97
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    Experimental brain research 70 (1988), S. 561-568 
    ISSN: 1432-1106
    Keywords: Rhythmic movement ; Licking ; Motor learning ; Hypoglossal activity ; Videorecording ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats trained to alternate between two adjacent drinking spouts (each spout is retracted after a single lick and presented again after the animal has licked at the other spout) emit 2.5 licks instead of the optimum 1 lick per spout presentation. The question whether the pacemaker of licking is reset or continues to run during transition between spouts was addressed in three experiments performed in 10 highly overtrained rats. Videorecording analysis of oro-facial activities showed that the rat's mouth was firmly closed during the 500 ms transition between spouts. EEG was recorded from the region of hypoglossal nucleus with implanted bipolar electrodes during continued licking at one spout and during spout alternation. Averaging (n = 256, 1024 ms) centered around the onset of the first lick at the newly contacted spout showed 2–3 lick related potentials in the post-transitional interval whereas only one such wave occasionally appeared at the end of the pre-transition period. Computer plotted distributions of post-transition licks (timed with respect to the last pre-transition lick) were examined while the horizontal or vertical distance between spouts was increased. Growing spout separation changed the height but not the timing of the modes of the post-transition lick distribution. This phase-locked synchronization of pre- and post-transition licks indicates that the central timing network of the lick generator is not reset but continues to run during transition between spouts and that the cessation of tongue movements is due to inhibition of the intracycle pattern generator and motor output. It is concluded that more sensitive recording techniques are required to detect the activity of the central timing network in absence of overt licking.
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  • 98
    ISSN: 1432-1106
    Keywords: Neurotransmitter ; Immunohistochemistry ; 3-D reconstruction ; Confocal microscopy ; Rat ; Lamprey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A new method for three-dimensional reconstruction of transmitter-identified neurons is presented which involves “en bloc” immunofluorescence histochemistry and confocal scanning microscopy. The technique was applied to different types of neurons in the rat brain and lamprey spinal cord. Thick sections or tissue “blocs” (50–200 μm thick) were incubated with antisera against neuropeptides or monoaminergic markers, followed by fluorescent secondary antibodies. Three-dimensional reconstructions were obtained by scanning the preparations in sequential focal planes with a thin laser beam, while sampling the emitted light in each focal plane. The method is convenient and can be applied to a wide variety of neuron types. The reconstructions obtained are accurate since the “optical serial sections” of the specimen are perfectly aligned, and optic disturbances such as “halo” phenomena do not occur.
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  • 99
    ISSN: 1432-2072
    Keywords: Butyrophenones ; Catalepsy ; Development ; Haloperidol ; Maturation ; Perphenazine ; Phenothiazines ; Ptosis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Developing rats are far more sensitive than adults to the behavioral effects of haloperidol. The present results support the hypothesis that this change may reflect age-related changes in brain responses such as alterations in drug-receptor or drug-effector mechanisms. Dose-response studies of catalepsy and ptosis were conducted in male Sprague-Dawley rats aged 30, 56, or 100 days. Resulting dose-effect curves were approximately parallel and showed rightward shifts with highly significant progressive increases of ED50. Similar developmental decreases in drug sensitivity (3–6 ×) were found following systemic (PO or IP) administration of haloperidol or the phenothiazine neuroleptic perphenazine, which differ markedly in structure, potency, distribution, and metabolism. Age-related decreases in drug sensitivity (3–4 ×) were also found using intracerebroventricular (ICV) administration of both agents in an attempt to bypass potential “pharmacokinetic” influences. Since the age-dependent decrease in sensitivity to both neuroleptics was found during the rising phase of drug action (1st hour) and ranked: PO〉IP〉ICV, some change in absorption and distribution of both drugs may occur in addition to the apparently important maturational decrease in target-organ sensitivity indicated by the responses to direct ICV injection and by the similarity of results obtained with dissimilar agents.
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  • 100
    ISSN: 1432-2072
    Keywords: 8-OH-DPAT ; Feeding ; Drinking ; Palatability ; Appetite ; Fenfluramine ; Satiety ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The 5-HT1A agonist 8-OH-DPAT, at a dose of 30 μg/kg, enhanced the consumption of sweetened wet mash and sweetened milk in non-deprived rats. In partially satiated rats, sensitivity to the hyperphagic effect of 8-OH-DPAT on wet mash intake was substantially increased, so that the minimally effective dose was reduced to 3 μg/kg. Similarly, 8-OH-DPAT was more efficacious in increasing milk intake in satiated rats. Thus, 30 and 40 μg/kg 8-OH-DPAT produced a 4-fold increase of milk intake in completely satiated rats compared to a 2-fold increase in partially satiated animals at a dose of 30 μg/kg. The increased intake of liquid and wet mash diets observed after treatment with low doses of 8-OH-DPAT argues against the involvement of non-specific gnawing in the increased consumption of solid food produced by the drug. Rather, the data suggest that 8-OH-DPAT may specifically stimulate appetite by counteracting a tonic serotonergic inhibition of feeding. The present experiments also showed that 8-OH-DPAT attenuates fenfluramine-induced anorexia which is thought to depend on increased serotonergic neurotransmission.
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