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S J Cooper

Publications and source records attributed to S J Cooper.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1989

The effects of the enantiomers of the dopamine agonist N-0437 on food consumption and yawning behaviour in rats.

The enantiomers of the potent and selective dopamine (DA) D-2 receptor agonist 2-(N-propyl-N-thienylethyl-amino)-5-hydroxytetralin, N-0437, were tested for their effects on palatable food consumption and yawning behaviour in rats. (-)-N-0437 (1.0 and 5.0 mumols/kg). This confirms the agonistic action of (-)-N-0437 on postsynaptic receptors as food consumption is considered to be related to stimulation of postsynaptic DA receptors. Yawning behaviour was stimulated by (-)-N-0437 (0.5 mumol/kg) and could be antagonized by the autoreceptor-selective antagonist (+)-UH 232 (25 mumols/kg), which suggests an agonistic action on DA autorecptors. (+)-N-0437 (5.0 and 10.0 mumols/kg) also reduced food consumption and the effect could be antagonized by YM 09151-2 (0.03 mumol/kg). The weaker effect of (+)-N-0437 on food intake in comparison to that induced by (-)-N-0437 can be explained if it assumed that (+)-N-0437 is a partial agonist. (+)-N-0437 did not induce yawning behaviour in rats, suggesting that autoreceptors mediating the release of DA may be involved in stimulating yawning by DA agonists.

Animals↗
PubMed1989

Microstructural analysis of the anorectic effect of N-0437, a highly selective dopamine D2 agonist.

Drug actions, mediated by dopamine D2 receptors, have been shown to reduce food consumption in rodents. The present study used a microstructural approach to feeding responses to determine the behavioural changes which underlie the anorectic effect of a selective D2 agonist, N-0437. Non-deprived male rats were trained to consume a palatable, sweetened mash in a 30 min test under familiar test conditions. N-0437 (1.0 and 3.0 mg/kg) significantly reduced food intake, but had no effect on the duration of feeding, the duration and frequency of feeding bouts, or on the time course of feeding. Its anorectic effect depended upon a selective reduction in the rate of eating. Microstructural analysis of other behavioural changes which followed treatments with N-0437 indicated that, at 0.3 mg/kg, the drug may have selective dopamine autoreceptor activity, but at 1.0 and 3.0 mg/kg it acts postsynaptically at D2 receptors. The results show that the anorectic effects of N-0437 can be clearly distinguished from the effects of psychomotor stimulants like D-amphetamine or cocaine, but they overlap in part with the effect of the mixed D1/D2 agonist, apomorphine. The results are discussed in relation to a proposed D2 receptor-mediation of one component of the behavioural changes that underlie feeding satiation.

Animals↗
PubMed1989

Effects of the imidazobenzodiazepine Ro 15-4513 on saccharin choice and acceptance, and on food intake, in the rat.

The general aim of the present series of experiments was to investigate the effects of the imidazobenzodiazepine, Ro 15-4513, on ingestional behavior in the rat. The more specific aims were to test its effects on preference for sweet taste, to determine if it acts as a benzodiazepine-receptor inverse agonist, and if it selectively reduces sweetness preference. The results indicated that Ro 15-4513 (1.0-10 mg/kg, i.p.) abolished the preference for a 0.05% sodium saccharin solution in a two-choice test. Water intake in the same test was unaffected. Second, at 10 mg/kg, it suppressed saccharin ingestion in an acceptance test; this effect was completely reversed by the selective benzodiazepine antagonist, Ro 15-1788 (20 mg/kg). Third, Ro 15-4513 (1.0-10 mg/kg) reduced palatable food consumption in non-deprived rats, an effect which was also antagonized by Ro 15-1788. The results are consistent the bidirectional modulation of ingestional responses to palatable taste stimuli as a consequence of drug actions at benzodiazepine receptors. Furthermore, they emphasize that any reduction in consummatory responses produced by Ro 15-4513 is likely to reflect inverse agonist characteristics, as distinct from any putative ethanol antagonist property.

Animals↗
PubMed1989

Evidence that d-fenfluramine anorexia is mediated by 5-HT1 receptors.

The effects of eight serotonin (5-HT) receptor antagonists on the anorectic effect of d-fenfluramine (3.0 mg/kg, IP) were examined in a test of sweet mash consumption, using non-deprived male rats. d-Fenfluramine's effect was attenuated by the mixed 5-HT1/5-HT2 receptor antagonists, methiothepin and metergoline; by the 5-HT2 receptor antagonist ritanserin; and by (+/-)cyanopindolol, a mixed 5-HT1A/5-HT1B receptor antagonist. In contrast, d-fenfluramine's effect was not antagonised by the 5-HT2 receptor antagonists ketanserin and ICI 169 369; the 5-HT3 receptor antagonist ICS 205 930; or by xylamidine, a peripheral 5-HT receptor antagonist. In this feeding model, none of the 5-HT antagonists, when tested alone, had any effect to increase palatable food consumption. The pattern of results obtained strongly suggest that central 5-HT1 receptors play an important role in the mediation of d-fenfluramine-induced anorexia.

Amidines↗
PubMed1989

Selective reduction by serotonergic agents of hypertonic saline consumption in rats: evidence for possible 5-HT1C receptor mediation.

Previously, it has been shown that, in small doses, putative 5-HT1A receptor agonists selectively increase ingestion of hypertonic saline without affecting either water or isotonic saline intake. Evidence was obtained in the present series of experiments for selective reduction in hypertonic saline following the administration of a variety of serotonergic directly- and indirectly-acting agonists. Water, isotonic saline (0.9%), or hypertonic saline (1.8%) were made available to separate groups of water-deprived rats. The results indicated some selectivity with the 5-HT-uptake inhibitor and releaser d-fenfluramine and the 5-HT uptake inhibitor fluoxetine, and with the 5-HT agonists mCPP [1-3-chlorophenyl)piperazine] and MK 212 [6-chloro-2-(1-piperazinyl)pyrazine]. In each case, hypertonic intake was significantly suppressed. Distinct from these compounds were TFMPP [1-(3-(trifluoromethyl)phenyl)piperazine], RU 24969 [5-methoxy-3-(1,2,3,6-tetrahydropyridinyl)1H-indole], and quipazine. This second group either reduced fluid intake indiscriminately or reduced water and isotonic saline drinking. Selective reduction in the intake of hypertonic saline did not occur. Finally, peripheral-administration of 5-HT or the 5-HT1B agonist CGS 12066B [7-trifluoromethyl-4(4-methyl-1-piperazinyl-pyrolo) (1,2-a) 1:2 maleate], had no significant effect on fluid intake in any fluid condition. The results are discussed in terms of a possible serotonergic mechanism which may underlie inhibition of hypertonic salt drinking, and which involves mediation through a subtype of the 5-HT1 receptor.

Animals↗
PubMed1989

Yawning induced by the selective dopamine D2 agonist N-0437 is blocked by the selective dopamine autoreceptor antagonist (+)-UH 232.

Yawning and stretching responses were elicited in rats by a small dose (0.3 mg/kg) of the highly selective dopamine D2 agonist, N-0437. The responses were blocked by the highly selective dopamine autoreceptor antagonist, (+)-UH 232 (3.0 mg/kg), but not by raclopride at a dose which selectively blocks postsynaptic D2 receptors. The results strongly confirm the view that yawning and stretching are behavioral responses elicited by stimulation of presynaptic D2 receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Effects of 5-hydroxytryptamine and d-fenfluramine on sham feeding and sham drinking in the gastric-fistulated rat.

Previous experiments indicated that drug treatments which increase serotonergic activity produce dose-related reductions in sucrose sham feeding. In the present studies, 5-hydroxytryptamine (5-HT, 2 mg/kg, IP) significantly reduced sham feeding; its effect was reversed by the peripheral 5-HT receptor antagonist, xylamidine (3 mg/kg, IP). At the same dose, 5-HT did not affect water sham drinking. These are the first data to implicate serotonergic activity at peripherally located 5-HT receptors in the modulation of sucrose sham feeding. d-Fenfluramine (3 mg/kg, IP) also reduced sham feeding, an effect that was weakly attenuated by xylamidine, suggesting substantial mediation of its effect by centrally located 5-HT receptors. Sham drinking was reduced by d-fenfluramine (3 mg/kg), although to a lesser degree. In comparison with the previous studies, the present data suggest that in smaller doses d-fenfluramine is relatively selective in its effect on sham feeding, but that, in larger doses, the selectivity may be lost.

Amidines↗