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Biomedical subjects

C Gentsch

Publications and source records attributed to C Gentsch.

At least 37 records · Page 2Linked to original sources
PubMed1994

Oxcarbazepine: preclinical anticonvulsant profile and putative mechanisms of action.

Oxcarbazepine (OCBZ, Trileptal) and its main human monohydroxy metabolite (MHD) protected mice and rats against generalized tonic-clonic seizures induced by electroshock with ED50 values between 13.5 and 20.5 mg/kg p.o. No tolerance toward this anticonvulsant effect was observed when rats were treated with OCBZ or MHD daily for 4 weeks. The therapeutic indices were 4 (OCBZ) and > 6 (MHD) for sedation (observation test, mice and rats) and 8 (MHD) or 10 (OCBZ) for motor impairment (rotorod test, mice). Both compounds were less potent in suppressing chemically induced seizures and did not significantly influence rat kindling development. At doses of 50 mg/kg p.o. and 20 mg/kg i.m. and higher, OCBZ and, to a lesser extent, MHD protected Rhesus monkeys from aluminum-induced chronically recurring partial seizures. In vitro, OCBZ and MHD suppressed sustained high-frequency repetitive firing of sodium-dependent action potentials in mouse neurons in cell culture with equal potency (medium effective concentration 5 x 10(-8) M/L). This effect is probably due in part to a direct effect on sodium channels. Patch-clamp studies on rat dorsal root ganglia cells revealed that up to a concentration of 3 x 10(-4) M, MHD did not significantly interact with L-type calcium currents, whereas OCBZ diminished them by about 30% at the concentration of 3 x 10(-4) M. In biochemical investigations, no brain neurotransmitter or modulator receptor site responsible for the anticonvulsant mechanism of action of OCBZ and MHD was identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Pretreatment with aldosterone or corticosterone blocks the memory-enhancing effects of nimodipine, captopril, CGP 37,849, and strychnine in mice.

Oral pretreatment with aldosterone or corticosterone blocked the memory-enhancing effects of the calcium antagonist nimodipine, the ACE inhibitor captopril, the NMDA blocker CGP 37,849, and the glycine antagonist strychnine in a passive-avoidance test in mice. The memory-disturbing effects of phenobarbitone, diazepam, CGP 37,849 and scopolamine were not influenced by the hormonal pretreatment. These findings could indicate the involvement of a steroid-sensitive mechanism in drug-induced improvement of memory. In the light of clinical observations showing elevated cortisol levels in Alzheimer patients, the results might also explain why only a limited number of these patients respond to therapy with memory enhancers.

2-Amino-5-phosphonovalerate↗
PubMed1991

Genetic and environmental influences on reactive and spontaneous locomotor activities in rats.

Paired groups of rats (derived from divergent, selective breeding or living in divergent environmental conditions) were compared with regard to locomotor activities. Intrapair differences were found to vary non-systematically, depending upon whether the rats were initially exposed to a test-environment with or without a slight environmental modification (reactive activities), or were allowed to habituate extensively to the environment (spontaneous activity). Since the behavioral patterns were found to represent distinct entities, this pointed to the necessity of differentiating clearly between spontaneous and reactive activities and indicated, once again, that both genetic and environmental influences are important in these behaviors and must be taken into account. Accepting and controlling for these variables makes it possible to use the factor of individual differences in laboratory animal behavior to advantage.

Animals↗
PubMed1990

Competition for sucrose-pellets in triads of male Wistar rats: disinhibitory effect of individual housing in poor-performing rats.

Within triads of male Wistar rats, some animals almost completely abstain from competition for palatable sucrose-pellets (so-called poor-performing rats). Individual housing temporarily helped these rats to behave more competitively. Such changes in the poor-performing rats' competition-scores are discussed in relation to previously described, isolation-induced alterations in serotonergic and noradrenergic neurotransmission.

Animals↗
PubMed1990

The pineal complex in Roman high avoidance and Roman low avoidance rats.

Previous studies have shown that the pineal gland of Roman high avoidance (RHA/Verh) rats is larger than that of Roman low avoidance rats (RLA/Verh). In the present study measurement of enzyme activities (serotonin-N-acetyl-transferase, hydroxyindole-O-methyltransferase) revealed that pineals of RHA/Verh rats are twice as active in melatonin production than pineals of RLA/Verh rats. Indoleamine content was also higher in RHA/Verh rats, whereas noradrenaline content was the same in both lines. When values were expressed per mg protein, these differences disappeared except for N-acetyl-serotonin and noradrenaline which were higher or lower in RHA/Verh rats, respectively. Both lines had higher serum levels of melatonin during the dark phase than during the light phase. However, RHA/Verh rats had increased serum levels as compared to RLA/Verh rats during both day and night. Morphometric analysis of the deep and superficial part of the pineal complex revealed, that the volumes of both parts are enlarged in RHA/Verh rats. Electron microscopic studies of pineals collected during day- and nighttime showed higher numbers of synaptic ribbons per unit area in pineals of RHA/Verh rats. In pineals collected during June synaptic ribbons displayed a day/night rhythm in RHA/Verh rats only, whereas in glands of both lines collected during November no daily changes were found. These results show that closely related but divergently selected rat lines may differ in pineal ultrastructure and pineal function.

Acetylserotonin O-Methyltransferase↗
PubMed1990

Competition for sucrose-pellets in triads of male Wistar rats: effects of acute and subchronic chlordiazepoxide.

Within triads of male Wistar rats, some animals almost completely abstain from competition for palatable sucrose pellets (so-called poor-performing rats), whereas other rats consistently win the competition (so-called high-performing rats). Subchronic (5 mg/kg; 5 consecutive days), but not acute (0.1-20 mg/kg), treatment with chlordiazepoxide temporarily helped poor-performing rats to behave more competitively. This finding, considered together with parallel studies (using high-performing rats), suggested that chlordiazepoxide's beneficial effect was only demonstrable when the poor-performing rats had become tolerant to the drug's initial sedative effect.

Animals↗
PubMed1989

Selective breeding in rats for extreme densities of platelet 3H-imipramine binding sites: evidence against a trait hypothesis.

Some investigators suggest that the number of platelet 3H-imipramine binding sites is genetically determined and that the reduced 3H-imipramine binding observed in some studies of depression represents a trait marker. Others believe that 3H-imipramine binding is state-dependent because 3H-imipramine binding has been reported to normalize after clinical recovery. We used a genetic selection paradigm in rats to approach this question from another direction. While breeding 10 generations of rats, we used either extremely high or extremely low density of platelet 3H-imipramine binding sites as a selection criterion. We were unsuccessful in producing two distinct rat sublines. These data do not support a predominant genetic influence on 3H-imipramine binding.

Animals↗
PubMed1989

Behavioral effects of yohimbine and chlordiazepoxide: dependence on the rat's previous familiarization with the test conditions.

The effects of yohimbine and chlordiazepoxide on locomotor activity in an open field were found to depend on the rat's previous habituation to the test environment: chlordiazepoxide induced a locomotor activation in nonhabituated, but not in habituated rats; yohimbine activated in habituated rats only. In a further study, carried out in the rat's homecage (habituated conditions), the effect of both drugs on competition for sucrose pellets was assessed: yohimbine, but not chlordiazepoxide, helped so-called poor-performing rats to temporarily overcome their typical abstention from competition. The presence or absence of drug effects, obviously depending on the rat's previous familiarization with the test environment, are discussed with view to Gray's concept of the behavioral inhibition system.

Animals↗
PubMed1988

Genetic and environmental influences on behavioral and neurochemical aspects of emotionality in rats.

Three pairings of rats (two derived from divergent, selective breeding and one from divergent environmental conditions) were compared with regard to behavioral and hormonal parameters. Striking differences were observed: results obtained in our own laboratory as well as those found in a review of the literature pointed to higher emotionality (e.g., increased defecation and corticosterone secretion, etc.) in Roman low-avoidance, Wistar-Kyoto and group-housed rats, as compared to their respective counterparts, Roman high-avoidance, spontaneously hypertensive, and individually housed Wistar rats. Concomitant receptor binding studies reviewed here (3H-diazepam- and 3H-imipramine-binding sites) have revealed, however, less consistent intrapair differences.

Animals↗
PubMed1988

Isolation-induced locomotor hyperactivity and hypoalgesia in rats are prevented by handling and reversed by resocialization.

Differences in locomotor activity in the open field were found between individually and group-housed rats (isol greater than soc). Daily handling, initiated at postnatal day 1, was without effect in group-housed rats but prevented the isolation-induced hyperactivity. For tail-flick latency, strikingly similar differences (isol greater than soc; prevention by handling) have been observed. The isolation-induced aberrations in both locomotor reactivity in a novel environment and in pain sensitivity could be reversed by subsequent resocialization. This indicates that the altered sensitivities to external stimuli are caused by the environmental manipulation.

Animals↗
PubMed1988

Competition for sucrose-pellets in triads of male Wistar rats: the individuals' performances are differing but stable.

After having individually been accustomed to consume palatable sucrose-pellets, the individual's competition-rate for sucrose-pellets within its familiar triad has been observed in male Wistar rats. In this fixed-triad, food competition paradigm high-performing rats (high competition-rate, majority of pellets consumed), medium-performing rats (medium competition-rate, consumption of some pellets) and poor-performing rats (almost completely abstaining from competition with only rare incidence of pellet consumption) can be distinguished. Intra-group rank-orders, defined according to the individuals' competition-rates (expressed as a score), were present in many triads and, once established, these were stable over months. No additional differences were observed between high- and poor-performing rats, neither when these were individually tested in an open field or in the elevated plus-maze, nor with regard to the preference for a sucrose solution.

Animals↗
PubMed1988

Competition for sucrose-pellets in triads of male Wistar rats: effects of three serotonergic drugs.

1. Within triads of rats, individuals can be discerned according to their competition for sucrose-pellets as a high-, a medium- and a poor-performing animal. 2. The competition-rates, expressed as scores, are affected by serotonergic drugs: upon inhibiting tryptophan-hydroxylase, the characteristic abstention of the poor-performing rats can temporarily be overcome; quipazine, on the other hand, leads to a dose-dependent decrease in the competition-rate of high-performing rats. 3. Such findings are indicative for a regulatory effect of some serotonergic mechanisms on a competition-behavior evoked within the familiar social context.

Animals↗
PubMed1987

Open field and elevated plus-maze: a behavioural comparison between spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats and the effects of chlordiazepoxide.

An interstrain comparison was conducted between male spontaneously hypertensive rats and Wistar-Kyoto rats, in both the open field and the elevated plus-maze. Wistar-Kyoto rats, as compared to the hypertensive animals, showed, beside an attenuated locomotor activity in both test situations, a higher reaction to aversive environments (less entries into the central area of the open field and less visits to the open arms of the elevated plus-maze). Chlordiazepoxide, as potent anxiolytic, increased (1) general activity, (2) the frequency of entries into the open area of the open field, and (3) the number of visits to the open arms of the elevated plus-maze in both rat strains.

Animals↗
PubMed1985

3H-Imipramine binding sites in platelets of hospitalized psychiatric patients.

The density of platelet 3H-imipramine binding sites has been proposed as a biological marker in psychiatry. We report the range of platelet 3H-imipramine binding in 55 psychiatric patients and 11 control subjects. All blood samples were withdrawn at 2300 h (on the day of hospital admission for patients). With the use of a slight modification of a previously described 3H-imipramine binding method, a mean B max of 1,510 fmole/mg protein (range: 390-5,560; median: 1,450) and a mean Kd of 2.0 nM (range: 0.6-17.0; median: 1.4) were determined for psychiatric patients. For the controls, a mean B max of 1,590 fmole/mg protein (range: 870-2,570; median: 1,440) and a mean Kd of 1.4 nM (range 0.8-2.4; median 1.4) were determined. When patients were subdivided based on ICD-9 psychiatric diagnoses, no significant differences between distinct subgroups of psychiatric patients with respect to B max or Kd values for platelet 3H-imipramine binding could be established. Similarly, no significant difference between psychiatric patients and controls was obtained.

Adolescent↗
PubMed1984

Differential response to cholinergic stimulation in psychogenitically selected rat lines.

Male and female rats of two lines psychogenetically selected for bipolar extremes in shuttle box avoidance were evaluated for tremor, salivation, chromodacryoorhea, and hypothermia following treatment with the muscarinic cholinergic agonist oxotremorine. Roman Low-Avoidance (RLA/Verh) rats exhibited more pronounced oxotremorine-induced tremor, chromodacryorrhea, and hypothermia than Roman High-Avoidance (RHA/Verh) rats. There was a sex difference only for a chromodacryorrhea response, with females exhibiting a greater response following oxotremorine than males. In a subsequent experiment using female rats of both rat lines, it was demonstrated that pre-treatment with the cholinergic antagonist scopolamine blocked oxotremorine-induced tremor, salivation and chromodacryorrhea responses in both rat lines and reduced the hypothermic effect observed in RLA/Verh rats (but not the much weaker hypothermia found in RHA/Verh rats) after oxotremorine injection. Pretreatment with the peripherally active cholinergic antagonist methscopolamine significantly reduced oxotremorine-induced salivation and chromocacryorrhea and somewhat decreased tremor and hypothermic responses in both rat lines. These results stand in contrast to the results of earlier research in which RHA/Verh rats exhibited greater behavioral depression in a tunnel maze than RLA/Verh rats following cholinergic manipulations. In view of evidence that these rat lines do not differ in number of muscarinic brain receptors, the present results may be due to genetic differences in other aspects of cholinergic neurotransmitter function, differences in the function of other neurochemical systems, or differences in the absorption, distribution, or metabolism of oxotremorine.

Animals↗
PubMed1984

3H-imipramine and 3H-cyano-imipramine binding in rat brain tissue: effect of long-term antidepressant administration.

3H-imipramine and 3H-cyano-imipramine binding was determined in brain homogenates of rats which had been treated for 21 days with imipramine or desimipramine. When compared to control animals, long-term administration of these antidepressants did not induce any alteration in the maximal number of 3H-imipramine or 3H-cyano-imipramine binding sites. However, a transient increase in the apparent dissociation constant was observed. Such findings are discussed in respect to previous studies, which have been highly contraversial.

Animals↗
PubMed1983

Individually housed rats exceed group-housed animals in rotational movements when exposed to a novel environment.

Individually and group-housed rats of both sexes were compared in respect to spontaneous rotational movements when exposed to a novel environment. Thereby, individually housed animals showed a higher number of rotational movements than group-housed controls. During an L12:D12 cycle, such movements occurred most frequently at the beginning of the dark phase, when locomotor activity was highest. It is assumed that these rotations are part of the hyperreactivity toward a novel environment induced by long-term individual housing.

Animals↗