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S J Cooper

Publications and source records attributed to S J Cooper.

At least 55 records · Page 3Linked to original sources
PubMed1996

Hyperphagia induced by direct administration of midazolam into the parabrachial nucleus of the rat.

Benzodiazepine receptor agonists increase food intake in many different species, yet there has been little investigation of the central site of actions of these drugs on ingestive behaviour. In the present experiments, direct administration of the benzodiazepine receptor agonist midazolam (3-30 micrograms/microliter) into the parabrachial nucleus of the pons significantly increased the consumption of a wet mash diet and a 3% sucrose solution in adult non-deprived rats. The hyperphagic response was blocked by pre-treatment with the selective benzodiazepine receptor antagonist flumazenil. Injection of midazolam into the parabrachial nucleus had no effect on locomotor activity, despite the fact that in the same animals an increase in mash intake was observed following intra-parabrachial midazolam. These data suggest that benzodiazepine receptors located in the parabrachial nucleus may be an important site of action for the effects of benzodiazepines specifically on ingestive behaviour.

Analysis of Variance↗
PubMed1996

d-fenfluramine's effects on normal ingestion assessed with taste reactivity measures.

The effects of d-fenfluramine on intake and on hedonic responses to taste stimuli in rats were investigated using a modified taste reactivity paradigm. Subjects (n = 15) were first trained to consume a 3% sucrose solution. They were then pretreated with d-fenfluramine (0.3-3.0 mg/kg, i.p.), and tested with access to either 3% sucrose, or a 0.01% quinine HCl solution. In the modified taste reactivity test, chronic oral cannulation was not used; instead, taste reactivity measures were scored during periods of noningestion in a voluntary intake test. d-Fenfluramine reliably reduced both sucrose and quinine consumption, and increased latency to drink at the highest dose. d-Fenfluramine also spared aversive responses to quinine, but reduced positive ingestive responses to sucrose. These results are consistent with an effect of d-fenfluramine to reduce taste palatability, which may, in turn, be an important factor in the effect of this drug on feeding motivation.

Animals↗
PubMed1996

Increased food intake following injection of the benzodiazepine receptor agonist midazolam into the IVth ventricle.

Despite a prolonged period of research with benzodiazepines, the central site(s) of action for the hyperphagic effects of these compounds remains to be determined. The aim of the present studies was to examine the effect of direct administration of the benzodiazepine receptor agonist midazolam into the IVth ventricle on ingestive behavior in nondeprived rats. In Experiment 1, microinjection of midazolam (3 and 30 micrograms/microliter) into the IVth ventricle was sufficient to increase consumption of a palatable mash. In Experiment 2, the hyperphagic effect was blocked by systemic administration of the selective benzodiazepine receptor antagonist flumazenil (20 mg/kg). The results indicate that a brainstem site of action may be important for the effects of benzodiazepine receptor agonists on ingestive behavior.

Animals↗
PubMed1996

Lack of interaction between devazepide and 8-OH-DPAT-induced hyperphagia in the rat.

Recently, a number of studies have provided evidence suggesting that CCK and 5-HT interact in the control of food intake. However, the majority of these studies have relied on the administration of exogenous CCK to investigate potential interactions. The aim of the present study was to focus on the potential role of endogenous CCK in 5-HT-CCK interactions. Our prediction was that the CCKA antagonist, devazepide, alone would potentiate the hyperphagic effect of the 5-HT1A agonist, 8-OH-DPAT, in free-feeding rats. The results showed that devazepide, at a dose that had no intrinsic effect (1.0 mg/kg), did not enhance the hyperphagic effect of 8-OH-DPAT (100 and 300 micrograms/kg). This suggests that when serotonergic inhibitory activity is reduced by 5-HT1A-receptor stimulation, there is no compensatory increase of endogenous CCK activity to excite 5-HT neurons and thereby inhibit food intake.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Membrane fatty acids, niacin flushing and clinical parameters.

Clinical definitions of schizophrenia are unreliable and difficult to use. The niacin flush test, which involves prostaglandin-induced vasodilatation, offers a method of exploring essential fatty acid metabolism in schizophrenic patients and may serve to define a subgroup of patients. In a multicentre study of schizophrenic patients with negative symptoms, we have examined the clinical accompaniments of the niacin response. Patients failing to flush with niacin showed significantly reduced levels of arachidonic and docosahexaenoic acids. Conversion from non-flushing to flushing during the 6 month supplementation period was predicted by an increase in arachidonic acid levels in red blood cell membranes irrespective of nature of supplementation. In this study, patients were selected for their negative symptoms and, therefore, it was not surprising that further measures of negative or positive symptoms did not predict flushing. However, an increased score for affective symptoms was significantly associated with a positive flush response. The stability of the niacin test needs to be examined in relation to the periodicity of symptoms in schizophrenia and manic depressive illness. New information on the anandamide system suggests that it may be associated with periodic phenomena and should be investigated in relation to the niacin test.

Adult↗
PubMed1996

Effects of the benzodiazepine receptor inverse agonist Ro 15-4513 on the ingestion of sucrose and sodium saccharin solutions: a microstructural analysis of licking behavior.

The effects of the benzodiazepine receptor partial inverse agonist Ro 15-4513 on consumption of either a 1% sucrose solution or a 0.1% sodium saccharin solution in nondeprived male rats was examined. A video-recording approach was adopted in which licks were counted in a frame-by-frame analysis. Ro 15-4513 (1-10 mg/kg) caused a significant decrease in the intake of both sucrose and saccharin solutions that was associated with a reduction in the initial rate of licking. There was a decrease in the total duration of drinking, total licks, and number of bouts for both sucrose and saccharin. For sucrose, mean bout duration was significantly reduced, although this was not so for saccharin. Intrabout lick rate, the latency to engage in drinking, and the postdrinking time were not affected for either sucrose or saccharin. These data are consistent with previous evidence that strongly suggests that benzodiazepines influence palatability.

Animals↗
PubMed1996

A molecular and evolutionary study of the beta-globin gene family of the Australian marsupial Sminthopsis crassicaudata.

Beta-globin gene families in eutherians (placental mammals) consist of a set of four or more developmentally regulated genes which are closely linked and, in general, arranged in the order 5'-embryonic/fetal genes-adult genes-3'. This cluster of genes is proposed to have arisen by tandem duplication of ancestral beta-globin genes, with the first duplication occurring 200 to 155 MYBP just prior to a period in mammalian evolution when eutherians and marsupials diverged from a common ancestor. In this paper we trace the evolutionary history of the beta-globin gene family back to the origins of these mammals by molecular characterization of the beta-globin gene family of the Australian marsupial Sminthopsis crassicaudata. Using Southern and restriction analysis of total genomic DNA and bacteriophage clones of beta-like globin genes, we provide evidence that just two functional beta-like globin genes exist in this marsupial, including one embryonic-expressed gene (S.c-epsilon) and one adult-expressed gene (S.c-beta), linked in the order 5'-epsilon-beta-3'. The entire DNA sequence of the adult beta-globin gene is reported and shown to be orthologous to the adult beta-globin genes of the North American marsupial Didelphis virginiana and eutherian mammals. These results, together with results from a phylogenetic analysis of mammalian beta-like globin genes, confirm the hypothesis that a two-gene cluster, containing an embryonic- and an adult-expressed beta-like globin gene, existed in the most recent common ancester of marsupials and eutherians. Northern analysis of total RNA isolated from embryos and neonatals indicates that a switch from embryonic to adult gene expression occurs at the time of birth, coinciding with the transfer of the marsupial from a uterus to a pouch environment.

Age Factors↗
PubMed1995

The putative dopamine D3 agonist, 7-OH-DPAT, reduces dopamine release in the nucleus accumbens and electrical self-stimulation to the ventral tegmentum.

The present experiments were designed to test further the idea that 7-OH-DPAT (7-hydroxy-N,N-di-n-propyl-2-aminotetralin), a putative dopamine (DA) D3 agonist, has effects at DA autoreceptors to reduce intracranial DA levels and to reduce behaviours that are DA-dependent. Rats were trained to respond on a self-stimulation protocol for electrical stimulation to the ventral tegmental area (VTA). Each press of a lever delivered a 0.5 s train of square wave, 1.5 ms duration, 100 Hz, 90-120 mA stimulation. Systemic administration of 7-OH-DPAT at 0.01-0.3 mg/kg i.p., quickly dose-dependently reduced responding. Electrical stimulation using similar parameters to those that supported self-stimulation were then applied to the VTA of anaesthetized rats. Fast cyclic voltammetry (FCV) revealed that this stimulation released DA in the nucleus accumbens (NAC). 7-OH-DPAT i.p. (0.1-3.0 mg/kg) quickly and potently reduced the size of the DA-generated voltammetric signal. This effect of 0.3 mg/kg 7-OH-DPAT was not blocked by sulpiride (60 mg/kg, i.p.) a D2-specific antagonist that may preferentially block D2 autoreceptors. These data are discussed with reference to the possibility that 7-OH-DPAT reduces the release of dopamine in the NAC, at D3, but not at D2, autoreceptors and that this in turn may reduce the rewarding effect of VTA stimulation.

Animals↗
PubMed1995

Dopamine receptor subtype agonists and feeding behavior.

Stimulation or blockade of various dopamine receptor subtypes is associated with reduced feeding. For example, D2 receptor agonists suppress feeding in food-deprived and free-feeding rats, and in rats given access to a highly palatable diet. Similarly, reduced food intake is associated with the actions of diverse D1 receptor agonists, and these compounds can interact synergistically with D2 receptor agonists to potentiate reductions in feeding. Using microstructural analysis to compare D1 and D2 agonist effects, specific differences emerge in their modes of action. D1 agonists reduce the duration of feeding, primarily by decreasing the frequency of feeding bouts, whereas D2 agonists reduce the local rate of eating. However, since D1 agonists uniquely reduce feeding in the absence of other behavioral impairments and are less disruptive of the pattern of feeding behavior, it has been suggested that D1 agonists are more likely than D2 agonists to act on central mechanisms regulating food intake. Moreover, only D1 agonists are effective in suppressing sucrose sham-feeding, suggesting that D1 receptor stimulation may promote satiety. Nevertheless, many questions remain. For example, antagonist studies have implicated 5-HT receptor stimulation in the anorectic effects of D1 agonists, suggesting that further pharmacological and behavioral analyses of receptor-subtype agonist effects are required. Above all, recent developments in the classification of dopamine receptor subtypes reveal the need for new studies examining the involvement of D3, D4 and D5 receptors in feeding.

Animals↗
PubMed1995

Benzodiazepines and palatability: taste reactivity in normal ingestion.

The taste reactivity (TR) test was devised as a method to obtain behavioural data in response to gustatory stimuli in neurologically impaired rats, incapable of voluntary feeding. Sapid solutions were infused through surgically implanted intraoral cannulae. Facial and motor responses corresponded well to known hedonic and aversive properties of tastes (e.g., sweet, bitter). TR testing has since proved effective as an adjunct to intake-based methods, in the psychopharmacology of ingestion in the normal rat. We developed a nonsurgical modification of the TR test, in which intact rats sampled stimuli voluntarily. The benzodiazepine receptor agonist midazolam (3.0 mg/kg, IP) was administered to rats first trained to consume a sweet 3% sucrose solution, and later tested with access to a bitter 0.01% quinine solution. Response were videotaped, and TR measures were scored during periods of noningestion using a frame-by-frame playback. Treatment increased ingestion and facilitated ingestive responses in accordance with published data for cannulated rats. Results support a two-component view of response palatability, in which treatment alters feeding motivation, increasing positive palatability and facilitating ingestion of both palatable and unpalatable stimuli.

Animals↗
PubMed1995

Opioid modulation of sucrose intake in CD-1 mice: effects of gender and housing conditions.

The effects of naltrexone (1 mg/kg, sc.) on consumption of a 5% sucrose solution were observed in nondeprived adult female CD-1 mice and in male mice. Males were either individually housed or were housed in pairs. Naltrexone significantly reduced the consumption of the sucrose in both female and male mice; in the case of the males the administration of naltrexone produced an intake pattern identical to that obtained for a less palatable (1.5%) sucrose solution in control conditions. There was no difference between subordinate and dominant males, neither in sucrose intake nor in the response to the naltrexone treatment. In a second experiment, it was shown that switching from a 5% to a 10% solution was sufficient to overcome naltrexone's suppressant effect in female mice, conversely this was not seen in the males. In general, the data are consistent with the view that opioid antagonists reduce effective palatability of sweet sucrose solutions in mice. There was no evidence that social isolation and stress related to subordination affected male mice's sucrose intake and response to the naltrexone challenge.

Animals↗
PubMed1995

Comparisons between the effects of 5-HT and DL-fenfluramine on food intake and gastric emptying in the rat.

5-Hydroxytryptamine (5-HT) dose-dependently increased gastric emptying in rats, whereas DL-fenfluramine produced a biphasic dose response curve for gastric emptying. Thus, fenfluramine increased gastric emptying at a dose of 0.1 mg/kg but decreased it at doses of 1 and 3 mg/kg. Both 5-HT and DL-fenfluramine produced significant decreases in food intake. As 5-HT produced opposing effects on gastric emptying and food intake, it appears that the anorectic effect of 5-HT may not depend on changes in the rate of gastric emptying. In contrast, doses of DL-fenfluramine that decreased feeding also decreased gastric emptying, which suggests that reduced food intake may at least partly result from decreased gastric emptying. Taken together, these results suggest that the effects of 5-HT and DL-fenfluramine on feeding and gastric emptying may be mediated by different mechanisms.

Animals↗
PubMed1995

7-OH-DPAT injected into the accumbens reduces locomotion and sucrose ingestion: D3 autoreceptor-mediated effects?

7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) injected bilaterally in the nucleus accumbens (NAC) resulted in profound, noncatatonic, dose-dependent (0.3-3 mg total dose) hypolocomotion but without inducing yawning. It also decreased intake of a highly preferred 3% sucrose solution (1 microgram total dose). Systemic injection of 7-OH-DPAT (0.1-3.0 mg/kg, i.p.) similarly induced hypolocomotion while failing to induce yawning. In none of these studies did rats show any signs of hyperlocomotion or any stereotyped responses normally associated with D2 or mixed D1/D2 receptor stimulation. These data suggest that hypolocomotion elicited by 7-OH-DPAT in the NAC may be mediated at the D3 receptor as distinct from the D2 dopamine receptor. We discuss the possibility that the behavioural effects we observed are mediated at D3 autoreceptors.

Animals↗
PubMed1995

Postglacial expansion and genome subdivision in the European grasshopper Chorthippus parallelus.

A noncoding nuclear DNA marker sequence (Cpn1-1) was used to investigate subdivision in the grasshopper Chorthippus parallelus and deduce postglacial expansion patterns across its species range in Europe. Investigation of the spatial distribution of 71 Cpn1-1 haplotypes and estimation of levels of genetic differentiation (KST values) between populations and geographic regions provided evidence for subdivision of C. parallelus into at least five major geographic regions and indicated that the French form of C. parallelus originated after range expansion from a Balkan refugium. Further evidence for subdivision of C. parallelus between Italy and northern Europe suggests that the Alps may have formed a significant barrier to gene flow in this grasshopper.

Animals↗
PubMed1994

Ondansetron, a selective 5-HT3 receptor antagonist, reduces palatable food consumption in the nondeprived rat.

This study investigated the effects of ondansetron, a selective 5-HT3 receptor antagonist, on palatable food consumption in nondeprived male rats, under conditions of familiarity. The results showed that ondansetron (3.0-30 micrograms/kg, i.p.) significantly reduced food intake at each dose tested. The reduction in food intake was due not to a change in the rate of eating but to a reduction in the time spent eating. This, in turn, was due to a reduction in the mean duration of feeding bouts but not due to a change in the frequency of feeding bouts. Hence, the feeding-suppressant effect of ondansetron resulted from a quite specific alteration in the microstructural characteristics of feeding behaviour. In the 60-min observation period, ondansetron did not affect either locomotor activity or rearing, indicating that it did not have general excitatory or behavioural-suppressant effects. Following ondansetron, animals continued to show a typical decline in feeding over time, indicative of the development of within-meal satiety, but the level of feeding was reduced in such a way as to suggest that ondansetron enhances satiety. As a result, as feeding declined, the level of grooming which typically follows the end of feeding, was increased in ondansetron-treated animals. In a supplementary experiment, ondansetron had no effect on deprivation-induced feeding. Present evidence does not allow these data for a 5-HT3 receptor antagonist to be easily accommodated into the major current hypothesis dealing with serotonergic control of feeding responses. Therefore, the role of 5-HT3 receptor-mediated changes in ingestive behaviour requires further investigation.

Animals↗
PubMed1994

Evidence for serotonergic involvement in saccharin preference in a two-choice test in rehydrating rats.

Adult male rats were adapted to a 20-h water-deprivation schedule and trained to drink a 0.1% sodium saccharin and water in a two-choice test (30 min). Several direct acting serotonergic receptor agonists (putatively agonists at the 5-HT2C receptor), MK212, mCPP, and TFMPP, respectively, blocked the saccharin taste preference normally exhibited in this test. Water intake was unaffected. Taken with earlier evidence that these drugs reduce salt taste preference in rehydrating rats, it appears that they may inhibit taste preferences more generally, and that this effect may be closely related to their well-documented anorectic effect. At 3.0 mg/kg, d-fenfluramine almost completely blocked the saccharin taste preference, although l-fenfluramine (0.3 and 1.0 mg/kg) exhibited only hyperdipsic effects. 5-HT creatinine sulphate (0.3-3.0 mg/kg) also produced hyperdipsic effects, but showed no sign of blocking sweet taste preference. As a positive control, it was also shown that the opioid receptor antagonist, naloxone, reduced saccharin taste preference.

Animals↗
PubMed1994

The selective dopamine uptake inhibitor GBR 12909: its effects on the microstructure of feeding in rats.

Previous experiments have investigated the anorectic effects of mazindol and cocaine, both of which can inhibit dopamine (DA) uptake into presynaptic terminals but do not do so selectively. GBR 12909, however, is an example of a potent and selective inhibitor of DA uptake and, therefore, the present study was concerned with investigating its possible effects on feeding behavior in nondeprived rats given access to a sweetened palatable diet. GBR 12909 (5-20 mg/kg, IP) was injected 2 h before a 60 min observation test. It produced a significant reduction in food intake, as a consequence of a reduction in the duration of feeding, without reducing the rate of eating. This anorectic profile is consistent with earlier findings for mazindol and cocaine. The other main behavioral effect of GBR 12909, observed in the present study, was to induce intense sniffing activity, but, unlike cocaine, it did not suppress grooming or induce hyperlocomotion. This selective behavioral effect of GBR 12909 indicates that sniffing can be isolated as one component of a broader array of components typically associated with DA-related stereotyped behavior.

Animals↗