Biomedical subjects

S J Cooper

Publications and source records attributed to S J Cooper.

At least 145 records · Page 8Linked to original sources

PubMed1987

Differential effects of CGS 8216 and naltrexone on ingestional behaviour.

Effects of the pyrazoloquinoline CGS 8216 (a partial benzodiazepine receptor inverse agonist) and the opiate antagonist, naltrexone, were compared in several tests of ingestion in non-deprived and deprived male rats. Both naltrexone (0.1-10.0 mg/kg, SC) and CGS 8216 (1.25-10.0 mg/kg, IP) significantly reduced the consumption of a highly palatable saccharin-glucose solution by non-deprived rats. Both compounds were also effective in reducing, dose-dependently, the intake of palatable sweet or oily mash by non-deprived animals. Hence, naltrexone and CGS 8216 attenuated palatability-induced ingestional responses, and sweet taste was not necessary for this effect to occur. The two drugs also reduced the intake of the saccharin-glucose solution in food-deprived rats, but their effects diverged in water-deprived animals. CGS 8216 had relatively little effect in the thirsty animals, whereas the effect of naltrexone was enhanced. This difference was underscored in a final test of deprivation-induced consumption of water. Naltrexone reduced the drinking, but CGS 8216 had no effect. Taken together, these data indicate that CGS 8216 was more selective in its effects on ingestion.

Animals↗

PubMed1987

Effects of the dopamine D-1 antagonist SCH 23390 and the D-2 antagonist sulpiride on saline acceptance-rejection in water-deprived rats.

Separate groups of water-deprived rats were familiarized with drinking water or one of a range of NaCl solutions (0.45-2.7%) in a 30 min test. The substituted benzamide, sulpiride, a selective dopamine D-2 receptor antagonist, significantly increased the consumption of water and hypotonic saline at 30 mg/kg. In contrast, the selective dopamine D-1 receptor antagonist, SCH 23390 (0.01-0.1 mg/kg SC) significantly reduced the intake of water and of saline at different concentrations in a dose-dependent manner. Consumption of water and 0.45% saline were most sensitive to the antidipsogenic effect of SCH 23390. These results suggest that previously-reported antidipsogenic effects of neuroleptics may depend, to at least some degree, on dopamine D-1 receptor blockade. The increase in drinking produced by sulpiride indicates that dopamine may act at D-2 receptors to inhibit the consumption of water and hypotonic saline, but not of stronger salt solutions.

Animals↗

PubMed1987

Bidirectional changes in the consumption of food produced by beta-carbolines.

beta-Carboline derivatives provide examples of benzodiazepine receptor ligands which span the range: full agonist-partial agonist-antagonist-partial inverse agonist-full inverse agonist. Taken together, the effects of these compounds illustrate two important principles: firstly, the bidirectionality of effects which can be achieved using benzodiazepine receptor ligands; secondly, the selectivity of effects which are produced by partial agonists. Applied to the study of feeding processes, these principles imply that both hyperphagic and anorectic effects can be generated by actions of selected ligands at benzodiazepine receptors. Furthermore, they suggest that a hyperphagic effect may occur in the absence of side-effects (e.g., sedation, muscle-relaxation), which are characteristic of classical benzodiazepines. Experimental data in support of these predictions are presented. A microstructural approach to feeding behavior indicated that a benzodiazepine receptor agonist and an inverse agonist extend and abbreviate, respectively, the duration of individual bouts of eating. Preference for a saccharin solution was attenuated by the beta-carboline inverse agonist, FG 7142, but rejection of a quinine solution was not increased. Adrenalectomy had no effect on the anorectic effect of inverse agonists.

Animals↗

PubMed1987

Rapid normalization of the dexamethasone suppression test with mianserin.

Dexamethasone suppression tests (DSTs) were carried out in 6 depressed patients and 2 with schizophrenia before and 48 to 72 hours after starting treatment. All 8 were non-suppressors before treatment but the 5 patients treated with mianserin and 1 treated with chlorpromazine had normal suppression with the repeat DST, unrelated to clinical change. Non-suppression persisted in the 2 patients treated with ECT or haloperidol. Mianserin and chlorpromazine could, therefore, be associated with false negative DST results. Possible mechanisms for this are discussed.

Chlorpromazine↗

PubMed1987

Can psychiatric nurses 'catch' schizophrenia?

The incidence of schizophrenia among psychiatric and general trained nurses was investigated for the period 1955-1979 in Northern Ireland. No difference was found. These results do not support the hypothesis of schizophrenia as a horizontally transmitted infectious disease.

Adult↗

PubMed1986

Paralysis with Ixodes cornuatus envenomation.

Ixodes cornuatus is a tick that is widely distributed in Victoria, Tasmania and southern New South Wales. Serious human envenomation has not been reported previously. The clinical syndrome that results from envenomation by Ixodes cornuatus in a three-year-old boy is presented. Bulbar palsy and respiratory failure necessitated endotracheal intubation and mechanical ventilation for five days. Canine tick antivenom was administered.

Animals↗

PubMed1986

Hyperphagic and anorectic effects of beta-carbolines in a palatable food consumption test: comparisons with triazolam and quazepam.

The triazolobenzodiazepine triazolam (0.1-1.0 mg/kg i.p.) and quazepam (0.3-30.0 mg/kg i.p.) were administered to non-food-deprived rats which had been partially-satiated on a palatable diet. In a subsequent 30 min feeding test, both compounds produced a significant increase in the level of food consumption. While triazolam had a dose-related effect and produced a 151.5% increase in the level of food intake, quazepam exerted only a partial effect, achieving a 73.9% increase in food intake at 3.0 mg/kg but no additional increase in food intake at higher doses. The two beta-carbolines, ZK 93423 (0.1-3.0 mg/kg i.p.) and ZK 91296 (1.0-30.0 mg/kg i.p.), a full agonist and a partial agonist at benzodiazepine receptors respectively, also produced significant increases in food consumption under the same experimental conditions. ZK 93423 had effects which were similar to those of triazolam, ZK 91296 had effects similar to quazepam. The beta-carboline benzodiazepine inverse agonist FG 7142 (10.0 mg/kg i.p.) had an anorectic effect in non-food-deprived rats given 30 min access to the highly palatable diet. This effect was reversed by the beta-carboline benzodiazepine receptor antagonist ZK 93426 in a dose-dependent manner. These results emphasize that within the series of beta-carboline ligands for benzodiazepine receptors, their characterization in terms of agonists, antagonists and inverse agonists has validity with respect to the behavioural response of palatable food consumption in non-food-deprived rats.

Animals↗

PubMed1986

Serotonergic mechanisms in brains of suicide victims.

Serotonergic mechanisms have been investigated in postmortem brain samples from controls and suicide victims. The concentrations of 5-hydroxytryptamine (serotonin; 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in occipital cortex and hippocampus and the high-affinity binding of ligands to the 5-HT1, 5-HT2 and imipramine-binding sites was assessed in frontal cortex, occipital cortex and hippocampus. The only significant difference between the two groups was a modest increase in 5-HIAA levels in the hippocampus of suicide victims. There was no evidence to suggest that those suicide victims with a clinical history of depression represented a subgroup with altered metabolite levels or binding values. The storage conditions of the samples were not related to the metabolite levels or binding values. There was, however, a significant positive correlation between [3H]imipramine binding and age in some brain regions. The results do not provide any evidence of gross alterations in 5-HT mechanisms in suicide or depression.

Adult↗

PubMed1986

An observational analysis of the effect of the selective kappa opioid agonist, U-50,488H, on feeding and related behaviours in the rat.

The behaviour of partially pre-satiated rats consuming a sweet palatable food and treated with either vehicle or the specific kappa receptor agonist U-50,488H (0.1-3 mg/kg) was recorded on videotape. Analysis revealed that the hyperphagia induced by the kappa agonist (0.3-3 mg/kg) resulted from an increase in the duration of feeding and not from an increase in the local rate of eating. The increase in duration was due, in turn, to a greater frequency of bouts of feeding. The kappa agonist also increased the latency to the final feeding bout. The effect of U-50,488H was consistent with de-satiation, so that the increase in feeding duration was in evidence from the start of the test period, while the temporal pattern of later satiation was preserved but lagged behind that of control animals. At the largest dose, other recorded activities (rearing, locomotor activity, grooming) were suppressed, with a marked increased in inactivity. At the lowest dose (0.1 mg/kg) there was a significant increase in grooming behaviour. The results are discussed with reference to an hypothesis of opioid function in the control of food intake.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1986

The effect of the beta-carboline FG 7142 on the behaviour of male rats in a living cage: an ethological analysis of social and nonsocial behaviour.

The effects of FG 7142, a beta-carboline benzodiazepine receptor partial inverse agonist, on the social behavior of pair-housed rats were investigated. Four 6-min dyadic social encounters in a living cage were observed in a paradigm in which one member of a pair of rats was injected. The four injection groups (n = 8) were vehicle control, and FG 7142 at 2.5, 5.0 and 10.0 mg/kg, respectively. All injections were administered 2 min before the start of the first observation trial. Compared to the effects of vehicle alone, FG 7142 decreased aggressive behaviour but did not change the level of total social interaction. Thus there were compensating increases in approaching and avoiding behaviours following the administration of FG 7142. Locomotion declined marginally and immobility increased in FG 7142-injected rats. FG 7142 decreased the incidence of self-grooming. The evidence is consistent with a relatively selective reduction in intraspecies aggression in male rats after the injection of the beta-carboline inverse agonist.

Aggression↗

PubMed1986

Benzodiazepine-induced hyperphagia: stereospecificity and antagonism by pyrazoloquinolines, CGS 9895 and CGS 9896.

Non-deprived male rats were familiarized with a highly palatable diet until baseline consumption in a 30-min daily access period had stabilised. Stereospecificity of the hyperphagic effect of benzodiazepine receptor agonists was demonstrated using two enantiomers, the (S)-enantiomer being Ro11-3128 (methylclonazepam) and the (R)-enantiomer, Ro11-3624. The benzodiazepine receptor antagonists, Ro15-1788 and CGS 8216, reversed the hyperphagic effect of Ro11-3128. These data confirm the mediation of the hyperphagic effect of benzodiazepines by specific receptors. In further experiments, the effects of the pyrazoloquinolines CGS 9895 and CGS 9896 were examined both alone and also in combination with clonazepam. In doses of 1.25-10.0 mg/kg, neither CGS 9895 nor CGS 9896, when given alone, had a significant effect on the consumption of the palatable diet. Both, however, dose-dependently antagonised the hyperphagic effect of clonazepam. In a test of palatable food consumption, therefore, both compounds can be characterised as benzodiazepine antagonists.

Animals↗

PubMed1986

Benzodiazepine receptor-mediated effect of CGS 8216 on milk consumption in the non-deprived rat.

The pyrazoloquinoline CGS 8216, which binds with high affinity to central benzodiazepine recognition sites, produced a highly significant reduction in the consumption of familiar, sweetened milk by non-deprived male rats, when administered in a dose of 20 mg/kg, IP. The anorectic effect was present during the first 5 min period of a 20-min drinking test, and remained in evidence throughout the remainder of the test. The benzodiazepine receptor antagonist Ro15-1788, administered 15 min before the consumption test, produced a dose-related (10-40 mg/kg, IP) reversal of the anorectic effect of CGS 8216, during the first 10 min of the test. Injection of Ro15-1788 alone had no significant effect on milk ingestion. This experiment shows that the reduction in the consumption of a palatable liquid food by CGS 8216 can be attributed to an action at benzodiazepine receptors. The result is consistent with the characterization of CGS 8216 as a weak benzodiazepine receptor inverse agonist.

Animals↗

PubMed1986

Effects of the beta-carboline FG 7142 on saccharin preference and quinine aversion in water-deprived rats.

Three groups of water-deprived male rats were given the choice of 0.05% sodium saccharin solution and water; 0.0005% quinine solution and water; water in both containers. N'-Methyl-beta-carboline-3-carboxamide (FG 7142), a benzodiazepine receptor inverse agonist, dose-dependently (2.5-10 mg X kg-1 i.p.) reduced intake of fluid in each group. The saccharin-choice group were most sensitive, showing a significant reduction at 2.5 mg X kg-1. Preference for the saccharin solution was reduced by FG 7142 but it did not increase aversion to the quinine solution. Hence, FG 7142 did not generally increase the rejection of flavoured solutions in a two-bottle test. A previously proposed "proconflict" effect of FG 7142 is discussed, in the light of these results.

Animals↗

PubMed1986

Naloxone antagonizes the hyperdipsic effect of sulpiride in a salt-preference test in male and female rats.

The consumption of saline and water in a two-bottle test of salt-preference was measured after the administration of sulpiride, a dopamine receptor antagonist and of naloxone, an antagonist at opiate receptors. The two drugs were injected alone, or in combination. Three concentrations of saline (0.125, 0.6 and 1.7% NaCl solutions) were used and the tests were carried out using both male and female, water-deprived rats. When the rats were allowed the choice between a highly-preferred 0.125% NaCl solution and water, sulpiride (30 mg kg-1, i.p.) produced an increase in the intake of the two fluids. When naloxone (1 mg kg-1, s.c.) was given alone, it had no effect in this test of salt preference, but when given in combination, completely eliminated the hyperdipsic effect of sulpiride, providing behavioural evidence of a significant interaction between sulpiride and naloxone. When choices of either 0.6 or 1.7% NaCl solutions and water were given, the baseline levels of the consumption of the fluids were increased. Under these circumstances, sulpiride did not significantly increase the consumption of fluids; instead, naloxone significantly reduced the level of fluid consumption. In a further experiment, apomorphine, at dose levels which stimulate dopamine autoreceptors, had no effect on either fluid intake or saline preference in water-deprived male rats. Biochemical data showing that dopamine inhibits the release of beta-endorphin in the hypothalamus through the dopamine D-2 receptor, suggests a possible mechanism for a blockade of sulpiride-induced hyperdipsia by naloxone.

Animals↗

PubMed1986

Dose-related response of male rats to apomorphine: snout contact in the open-field.

Apomorphine (0.01 to 5 mg/kg, SC) was administered to male rats observed singly in the open-field. The behavior of each rat was coded using a microprocessor during 3 preinjection and 9 postinjection trials of 6 min duration over a 2 hr session. The behavior categories included grooming, yawning, turning, nodding and gnawing, as well as snout contact and nonsnout contact variants of locomoting, rearing and sitting. Dose-dependent increases in the time spent in snout contact with the field surface were noted throughout the complete dose range. Both the peak and duration of the snout contact epoch increased with the dose of apomorphine. The integrated time spent in all types of snout contact proved to be the best behavioral measure for discriminating between doses of apomorphine even though the topography of snout contact response changed as a function of the dose.

Animals↗

PubMed1986

CGS 8216, a novel anorectic agent, selectively reduces saccharin solution consumption in the rat.

The pyrazoloquinoline CGS 8216, a high-affinity ligand for benzodiazepine recognition sites, significantly reduced the consumption of a preferred 0.05% sodium saccharin solution in a 30 min two-bottle test. A highly significant effect was detected at 5.0 mg/kg, IP and at higher doses. The consumption of water and 0.6% saline, in two-bottle tests, or of quinine solution and water, in a forced-choice test, was not reliably affected by CGS 8216. The results point to a sensitive and selective intrinsic effect of CGS 8216 on ingestional responses in the rat.

Animals↗

PubMed1986

Midazolam-induced hyperphagia and FG 7142-induced anorexia: behavioural characteristics in the rat.

Non-deprived male rats, familiarized with a highly palatable diet, were treated with 0.3-10.0 mg/kg of the imidazobenzodiazepine midazolam. The increases in consumption of the food observed at larger doses of midazolam were due to increases in the duration of feeding, but not in the rate of eating. These, in turn, were due to increases in the duration of eating bouts, but not in their frequency. The beta-carboline FG 7142, a partial benzodiazepine receptor inverse agonist, reduced the consumption of the diet when it was injected at 10.0 and 15.0 mg/kg (IP). The overall duration of feeding was not affected at these doses in the 30 min test, but rate of eating was reduced. However, during the first 5 min interval of the test, when feeding behaviour was most motivated, FG 7142 did significantly reduce the duration of feeding. The effect depended upon a reduction in the duration of eating bouts, but not upon any change in their frequency. Hence, midazolam and FG 7142 had opposite effects on the duration of bouts of feeding. Both midazolam and FG 7142 reduced the frequencies of concurrent grooming, locomotor activity, and rearing in the test of palatable food consumption. Possible explanations for these effects are briefly considered.

Animals↗

PubMed1986

beta-Carboline FG 7142-reduced aggression in male rats: reversed by the benzodiazepine receptor antagonist, Ro15-1788.

The beta-carboline FG 7142 decreases conspecific aggression in male hooded rats. The purpose of this study was to examine the effects of pretreatment with Ro15-1788 or chlordiazepoxide (CDP) in this paradigm. The six groups (n = 8) were saline, FG 7142 (5 mg/kg, immediate, IP), CDP (5 mg/kg, -10 min, IP), CDP (5 mg/kg, -10 min) plus FG 7142 (5 mg/kg, immediate), Ro15-1788 (10 mg/kg, -10 min, IP), and Ro15-1788 (10 mg/kg, -10 min) plus FG 7142 (5 mg/kg, immediate). Following injection of the more aggressive member of a pair of isolation-housed rats, the pair was observed in a living cage over four 6-min trials interpolated over a 40 min session. In the first 20 min after the injection FG 7142 decreased aggression, decreased the pinning of the other animal, and increased avoiding behavior. These effects were the opposite of those seen in the Ro15-1788-injected rats and Ro15-1788 pretreatment reversed the effects of FG 7142. CDP alone caused prolonged aggressive behavior but as a pretreatment only partially reversed the effects of FG 7142.

Aggression↗