PubMed Health⌕ Search

Biomedical subjects

S J Cooper

Publications and source records attributed to S J Cooper.

At least 19 recordsLinked to original sources
PubMed1992

The beta-carboline abecarnil, a novel agonist at central benzodiazepine receptors, influences saccharin and salt taste preferences in the rat.

Abecarnil is a recently described beta-carboline which acts at central benzodiazepine receptors (BZR) and has anxioselective/anticonvulsant properties. While it may be classified provisionally as a partial agonist at BZR, there is also evidence that its pharmacological profile may be due to a selective action at BZR subtypes. The general aim of the present series of experiments was to investigate the effects of abecarnil on ingestional behaviour in the rat. The results indicated that abecarnil (0.3-10 mg/kg, i.p.) selectively increased the intake of preferred 0.05% sodium saccharin and 0.9% sodium chloride solutions in two-choice tests using water-deprived rats. These results confirm and extend previous work with the potent BZR agonist clonazepam. Moreover, abecarnil significantly increased the ingestion of sweetened mash and 3% sucrose solution in nondeprived animals. In general, these results indicate that abecarnil is effective in increasing ingestional responses, a characteristic it shares with classical agonists like diazepam. The results could be accounted for in terms of a partial agonist profile for abecarnil, but do not rule out the possibility of selective actions at BZR subtypes.

Animals↗
PubMed1992

5-Hydroxyindoleacetic acid in cerebrospinal fluid and prediction of suicidal behaviour in schizophrenia.

Low concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) are associated with suicidal behaviour in patients with depressive illness, but studies of the relation between CSF 5-HIAA and suicide in schizophrenia have been inconclusive and have not included long-term follow-up. In a prospective study, we measured 5-HIAA in CSF taken from 30 schizophrenic patients in a drug-free state, and followed these patients for 11 years. 10 patients made suicide attempts during follow-up. Suicide attempters had significantly lower concentrations of CSF 5-HIAA at initial evaluation than non-attempters (mean [SE] 6.7 [2.2] vs 23.6 [5.6] ng/ml, p < 0.05). Our findings provide further evidence of the relation between serotoninergic dysfunction and suicide, and suggest a role for drugs with serotoninergic effects in schizophrenia.

Female↗
PubMed1992

A placebo controlled trial of remoxipride in the prevention of relapse in chronic schizophrenia.

Sixty-two DSM III chronic schizophrenic inpatients were selected for a double-blind, placebo controlled, multi-centre, relapse prevention study of remoxipride, a selective dopamine (D2)-receptor antagonist. After a 1 month placebo washout, 23 patients had relapsed and were withdrawn. Of the remaining patients 19 were randomised to remoxipride (150-300 mg daily) and 20 to placebo. Their median age was 58 years, 26 were male, and the median duration of illness was 33 years. After 24 weeks a further total of 8 remoxipride and 17 placebo patients had been withdrawn. Excluding three patients withdrawn for reasons other than relapse, the comparative relapse rates were 37% and 75%, respectively (P = 0.015). Efficacy analyses using clinical global impression (P = 0.04) and change in BPRS scores (P = 0.016) were in favour of remoxipride. Extrapyramidal symptoms were minimal in both groups. Treatment emergent adverse events were similar in the two groups. Remoxipride is therefore of potential value as a safe drug which is both effective and well tolerated in the long term management of chronic schizophrenic patients.

Adult↗
PubMed1992

Behavioural pharmacology of 5-HT3 receptor ligands.

Extensive studies have ascribed a role for the central 5-HT3 receptor in the modulation of behaviour. Much of the work stems from the actions of potent and selective 5-HT3 receptor antagonists; these agents reduce mesolimbic dopamine initiated hyperactivity, release suppressed behaviour, reduce the reinforcing properties and withdrawal symptoms of drugs of abuse, enhance cognitive performance and modulate appetite. This article reviews the preclinical and clinical evidence implicating the 5-HT3 receptor in these indications and discusses the potential neurochemical mechanisms underlying the behavioural changes.

Animals↗
PubMed1992

CCK antagonists and CCK-monoamine interactions in the control of satiety.

The introduction of potent cholecystokinin (CCK) receptor antagonists, selective for either the CCK-A or the CCK-B subtype, has provided a great impetus to the study of activity of endogenous CCK in relation to the control of feeding. This paper reviews experiments in which devazepide (a selective CCK-A receptor antagonist) and L-365,260 (a selective CCK-B-gastrin receptor antagonist) have been used. Both compounds increase food consumption (under certain conditions) and postpone the onset of satiety. L-365,260 is the more potent, suggesting a role for central CCK-B type receptors in satiety. In addition, use of CCK antagonists permits the study of important functional interactions between CCK and other neurochemical factors that serve to control feeding. Thus, devazepide, but not L-365,260, blocked the anorectic effect of either d-fenfluramine or serotonin. Hence, CCK-A type receptors appear to be involved in the anorectic effect of these drugs. This result serves as an example to illustrate a principle of cooperativity in the satiety-inducing effects of diverse neurochemical signals.

Animals↗
PubMed1992

Schizophrenia after prenatal exposure to 1957 A2 influenza epidemic.

"The birth dates of schizophrenic inpatients in eight health regions in England and Wales were reviewed for any effect of the 1957 A2 influenza epidemic. 5 months after the peak infection prevalence, the number of births of individuals who later developed schizophrenia was 88% higher than the average number of such births in the corresponding periods of the 2 previous and the next 2 years. This finding is in accordance with a study from Helsinki and with clinical and neuropathological evidence of aberrant fetal brain development in the pathogenesis of schizophrenia."

Disease Outbreaks↗
PubMed1991

Effects of dopamine D1 and dopamine D2 antagonists on the free feeding and drinking patterns of rats.

In male rats with food and water freely available, the specific dopamine D2 antagonist YM-09151-2 had little effect on total food or water intake across a 24-hr period. However, it produced a substantial dose-related decrease in feeding rate during meals and an enhancement of both meal size and duration. The equivalent parameters for water intake were affected to a much lesser extent. A second dopamine D2 antagonist, remoxipride, had similar effects on feeding patterns and, in addition, raised food intake during the 2 hr after drug administration. A third dopamine D2 antagonist, raclopride, produced a short-lived rise in food intake and a slowing of feeding rate with a nonsignificant increase in meal size at intermediate doses. Higher doses increased the latency to feed and drink. The specific D1 antagonist SCH 23390 had small effects on both total food intake and feeding patterns. Water intake was substantially reduced in the first 2-4 hr after drug administration by an increased latency to drink. The results are interpreted, first of all, in terms of two separate effects of dopamine D2 receptors on feeding behavior: the first mediating positive feedback processes important at meal initiation and the second mediating the preabsorptive effects of food on meal termination. D1 receptors, in contrast, are of greater importance in controlling water intake.

Animals↗
PubMed1991

The clinical correlates of neurological soft signs in chronic schizophrenia.

Among 16 chronic schizophrenic in-patients, all had at least one neurological soft sign (NSS), and 6 (40%) had definite neurodysfunction. NSS and TD scores were highly intercorrelated, and NSS were significantly correlated with neuroleptic drug exposure. NSS correlated positively with both positive and negative symptoms and cognitive impairment but not with cerebral ventricular size on CT. Patients with neurodysfunction had more positive and negative psychopathology, cognitive impairment and TD than those without. Cerebral ventricular sizes and family histories of schizophrenia were similar in both NSS groups. The presence of NSS may be a simple but important way of identifying a subgroup of schizophrenics with neurodevelopmental predisposing abnormalities, and vulnerability to TD.

Adult↗
PubMed1990

The anorectic effect of SK&F 38393, a selective dopamine D1 receptor agonist: a microstructural analysis of feeding and related behaviour.

An observational study was undertaken to provide a microstructural analysis of the effects of the selective dopamine D1 receptor agonist, SK&F 38393, on feeding and associated behaviours in the rat. Adult, male non-deprived rats were adapted to eating a meal of sweetened mash in a 30-min period. SK&F 38393 (3.0 and 10 mg/kg, SC) significantly reduced food consumption). It also reduced the frequency of feeding bouts and the local rate of eating, while there was an increase, at 10 mg/kg, in the mean duration of individual feeding episodes. The D1 receptor agonist also reduced the total duration of locomotor activity, but did not affect the total duration of rearing, grooming, sniffing, oral behaviours (other than feeding), or resting. The frequency of bouts of locomotion, rearing, grooming, and sniffing were reduced by SK&F 38393. Consideration of the time-courses for the several responses suggested that SK&F 38393 did not materially affect the form and sequence of behavioural responses in the test, although some changes occurred.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Multiple cholecystokinin (CCK) receptors and CCK-monoamine interactions are instrumental in the control of feeding.

Almost two decades ago, exogenous cholecystokinin (CCK) was shown to suppress food consumption in rats. Since then, CCK has been detected not only in peripheral tissue but extensively throughout the central nervous system. Furthermore, specific CCK receptors have been described, and a distinction drawn between CCK-A and CCK-B receptors. Recently, potent, orally active CCK antagonists, which show a high degree of selectivity for either CCK-A or CCK-B receptors, have been introduced. The present report reviews recent evidence obtained in studies using devazepide (a selective CCK-A receptor antagonist) and L-365,260 (a selective CCK-B/gastrin receptor antagonist). Both compounds increased food consumption and postponed the onset of satiety in well-satiated rats. L-365,260 was more potent, suggesting that central CCK-B type receptors may mediate the satiety effects of endogenously released CCK. Only devazepide was effective in blocking the feeding-suppressant effect of exogenous CCK, indicating that CCK-A type receptors mediate this effect. In a second series of studies, devazepide but not L-365,260 antagonized the anorectic effect of either d-fenfluramine or systemically administered 5-HT. Hence, CCK-A type receptors appear to be involved in the anorectic effects of these serotonergic drugs. We propose that CCK and 5-HT mechanisms involved in mediating satiety are mutually interdependent. Possible interactions between CCK and catecholaminergic mechanisms are also briefly considered.

Animals↗
PubMed1990

Fluoxetine reduces food intake by a cholecystokinin-independent mechanism.

The selective serotonin uptake inhibitor, fluoxetine (3.0-10 mg/kg), produced a significant dose-related suppression of palatable food consumption in nondeprived rats. The anorectic effect of fluoxetine (10 mg/kg) was not reversed by the potent and highly selective cholecystokinin receptor antagonist MK-329 [1-methyl-3-(2-indolyl) amino-5-phenyl-3H-1,4-benzodiazepin-2-one], administered in doses of 10-100 micrograms/kg. Fluoxetine (10 mg/kg) also significantly reduced the consumption of powdered laboratory chow in a 6-hr nocturnal free-feeding test. The anorectic effect in this paradigm was also not antagonized by MK-329. In contrast to previous data for d-fenfluramine (which enhances serotonin release), these results indicate that fluoxetine may suppress food intake by a mechanism which is independent of endogenous cholecystokinin.

Animals↗
PubMed1990

SCH 23390-induced hypophagia is blocked by the selective CCK-A receptor antagonist devazepide, but not by the CCK-B/gastrin receptor antagonist L-365,260.

The selective dopamine D-1 receptor antagonist SCH 23390 (30 micrograms/kg, SC) significantly reduced palatable food consumption by nondeprived rats in a 30-min test period. Prior administration of the selective CCK-A receptor antagonist devazepide (MK 329; L-364,718) blocked the hypophagic effect of SCH 23390. In contrast, prior administration of the selective CCK-B/gastrin receptor antagonist L-365,260 had no effect. Devazepide did not antagonize a matched hypophagic effect produced by the dopamine D-2 receptor antagonist raclopride (0.1 mg/kg, SC). These data direct attention to possible dopamine-cholecystokinin interactions in relation to the control of ingestional responses, and, more specifically, indicate possible functional relationships between D-1 and CCK-A receptor mechanisms.

Animals↗
PubMed1990

Beta 2-adrenoceptor antagonism in anxiety.

The relative role of beta 1- and beta 2-adrenoceptor antagonism in the management of anxiety symptoms is not clear. We studied the effect of ICI 118,551, a selective beta 2-antagonist, in 51 patients presenting with acute anxiety symptoms and fulfilling DSM-III criteria for anxiety disorder. All patients received placebo during the first week of treatment followed by thrice daily diazepam (2 mg) or ICI 118,551 (50 mg) or placebo for 4 weeks with double-blind, random allocation. Hamilton anxiety scale scores improved on all treatments but there was no significant difference between treatments. Beta 2-adrenoceptor antagonism does not appear to be effective in acute anxiety neurosis. Some earlier literature suggests that beta 1-antagonism may be more important.

Adrenergic beta-Antagonists↗
PubMed1990

Reversal of the anorectic effect of (+)-fenfluramine in the rat by the selective cholecystokinin receptor antagonist MK-329.

1. Experiments were conducted to determine whether or not the effect of (+)-fenfluramine (3.0 mg kg-1, i.p.) on food intake can be antagonized by the selective cholecystokinin receptor antagonist MK-239 (formerly L364,718; (3S(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1-H-1,4-benzodiazepin++ +-3-yl)-1H- indole-2-carboxamide). Two feeding paradigms were employed. In the first, non-deprived rats were familiarized with eating a highly palatable, sweetened mash in a 30 min test. In the second, freely-feeding rats were trained to consume powdered chow in their home-cages, and their intake was monitored over the first 6 h of the night-period. 2. In doses of 30.0 and 100.0 micrograms kg-1, s.c., MK-329 almost completely blocked the anorectic effect of (+)-fenfluramine in the palatable food intake test. These doses of MK-329 have previously been reported to antagonize the anorectic effect produced by exogenous cholecystokinin-octapeptide (CCK8) in rats. Both doses of MK-329 were also effective in significantly attenuating the anorectic effect of (+)-fenfluramine in nocturnal free-feeding animals over a 6 h-period. 3. MK-329 (10.0-100.0 micrograms kg-1, s.c.) failed to antagonize the anorectic effect of either the specific dopamine D2-receptor agonist quinpirole (0.3 mg kg-1, s.c.) or the beta-carboline FG 7142 (10.0 mg kg-1, i.p.) in the palatable food intake test. 4. MK-329 (10.0-300.Opgkg-1, s.c.) had no effect, when administered alone, on the level of palatable food intake in non-deprived rats, even when substantial satiation was produced by a pre-feeding procedure. Furthermore, MK-329 had no effect, when administered alone, on nocturnal food intake in freelyfeeding rats. 5. In conclusion, not only was MK-329 a potent antagonist of the effect of CCK8 on food intake, it also blocked the effect of (+)-fenfluramine to a significant degree. The effect of MK-329 was selective in that the anorectic effects of either quinpirole or FG 7142 remained unaffected. Administered alone, MK-329 did not affect food intake, indicating that its reversal of (+ -fenfluramine-induced anorexia was not secondary to an intrinsic hyperphagic effect. The results provide some evidence that the depressant effect of (+ )-fenfluramine on food intake depends on the activity of endogenous CCK.

Animals↗
PubMed1990

A neuroendocrine view of ECT.

"A neuroendocrine hypothesis to explain the clinical activity of convulsive therapy is described. The hypothesis is based on the diabetes/insulin model and suggests that hypothalamic dysfunction with an insufficiency of a mood-maintaining peptide is the basis for affective disorders. Repeated seizures enhance the production and release of the hypothalamic peptide antidepressin - the active principle that relieves both neuroendocrine and behavioral abnormalities.

Bipolar Disorder↗