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S J Cooper

Publications and source records attributed to S J Cooper.

At least 181 records · Page 10Linked to original sources

Effects of kappa opiate agonists on palatable food consumption in non-deprived rats, with and without food preloads.

There is increasing evidence to suggest that kappa opiate receptors may be importantly involved in the mediation of feeding responses in the rat. A series of experiments is reported in which the effects of four kappa receptor agonists (ethylketocyclazocine, U-50,488H, tifluadom, bremazocine) on the consumption of a highly palatable diet were investigated. Under one condition, non-deprived male rats were administered drug treatments before a 30 min feeding test. Bremazocine (0.1 mg/kg) and ethylketocyclazocine (3.0 mg/kg) both significantly decreased the level of food consumption. In contrast, U-50,488H and tifluadom each produced significant increases in food intake. In a second condition, non-deprived male rats were first allowed to consume some of the palatable diet to achieve partial satiation, prior to the administration of the drug treatments. In this case, evidence for hyperphagic effects of all four kappa agonists was obtained, within the first 30 min access to the palatable diet. Thus, hyperphagia occurred with 0.01 mg/kg bremazocine and 0.1 mg/kg ethylketocyclazocine. We conclude that some kappa agonists have mixed stimulant/inhibitory effects on food intake, whereas others are more consistent in producing hyperphagia. In neither condition did morphine (0.3-10.0 mg/kg) show any hyperphagic effect. Our data support an involvement of kappa opiate receptors in mechanisms which control palatable food consumption in non-deprived rats.

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

Bidirectional control of palatable food consumption through a common benzodiazepine receptor: theory and evidence.

A classical approach to the control of food consumption has been to assume separate mechanisms for the arousal to eat, on the one hand, and the satiation of feeding responses, on the other. The present paper is concerned with a single, and a comparatively simple, neuronal mechanism which is endowed with properties to allow the complete determination of the level of feeding, from hyperphagia to anorexia. The model for the control of feeding, which is presented here, draws attention to the benzodiazepine receptor found distributed through the brain, and present in certain hypothalamic nuclei. Recent evidence which characterizes the receptor is reviewed, and the various categories of benzodiazepine receptor ligands are described. Pharmacological data, collected in a palatable food consumption model using non-food-deprived rats, demonstrate that benzodiazepine receptor agonists produce hyperphagia, benzodiazepine receptor inverse agonists produce anorexia, and benzodiazepine receptor antagonists block both effects. Hence, bidirectional control of food intake can be achieved through differential ligand action at a common set of receptors. Speculatively, these data can be extended, if it is assumed that two endogenous ligands exist in the brain which act like benzodiazepine agonist and inverse agonist, respectively. Evidence for the presence in hypothalamic nuclei of endogenous ligands of the latter kind is discussed. Benzodiazepine withdrawal-induced anorexia is also described, and is taken as evidence for the part played by feeding mechanisms in the development of benzodiazepine physical dependence.

Animals↗

Alphavirus neurovirulence: monoclonal antibodies discriminating wild-type from neuroadapted Sindbis virus.

Wild-type Sindbis virus strain AR339 (SV) and a neurovirulent mutant (NSV), derived by neonatal and weanling mouse brain passage, both cause acute fatal encephalitis in neonatal mice, but NSV alone kills adult mice. NSV cannot be distinguished from SV by immune sera or simple biochemical tests. To localize the molecular changes associated with neuroadaptation, we used a new array of 30 anti-SV monoclonal antibodies to probe for differences between SV and NSV in four tests: immunoprecipitation, enzyme-linked immunosorbent assay binding, neutralization, and hemagglutination inhibition. Seventeen monoclonal antibodies detected differences. Both E1 and E2 glycoprotein gene products were altered during neuroadaptation, but the preponderance of changes was clustered on E2. The capsid protein C was not measurably altered. Mapping of both viruses with these monoclonal antibodies showed that during neuroadaptation SV topography substantially shifted, masking and unmasking biologically important neutralization and hemagglutination inhibition sites. These conformational rearrangements, predominantly on E2, coincided with the acquisition of increased neurovirulence and new lethality for adult mice.

Antibodies, Monoclonal↗

Adrenergic receptors in depression. Effects of electroconvulsive therapy.

Platelet alpha 2-and lymphocyte beta 2-adrenoceptor densities, plasma noradrenaline and serum cortisol were measured before, during and one week after a course of EEG-monitored electroconvulsive therapy, in nine depressed patients. A 50% fall in Hamilton Depression Rating scores occurred after a fairly consistent total seizure time, regardless of the amount of ECT given. Platelet alpha 2-adrenoceptor densities showed a statistically significant fall after three ECTs, but were unchanged after the full course of ECT and were independent of clinical change. Lymphocyte beta 2-adrenoceptor densities were unaltered. Plasma noradrenaline concentrations were initially high, and fell with ECT in a manner paralleling clinical recovery. Plasma noradrenaline may be a more useful index of central changes during antidepressant treatment than peripheral blood cell receptor densities.

Adult↗

A survey of serum antibodies to eight common viruses in psychiatric patients.

Serum antibody titres to eight neurotropic viruses were measured by enzyme immunoassay in 450 psychiatric in-patients and 143 controls. A seasonal variation in schizophrenic births was observed, with a peak incidence between March and April. Both herpes simplex virus and cytomegalovirus antibody titres correlated with age and, when this was controlled for, no significant differences emerged between any patient group and the controls. Mumps antibody titres were significantly lower in patients with mental subnormal and neurosis or personality disorder; measles and rubella antibody titres were lower in male but not female mentally handicapped patients; males had lower antibody titres to mumps, cytomegalovirus and Epstein-Barr virus than females in all groups. A decrease in mumps antibody titres was also found in schizophrenics if the medication factor was excluded. These low antibody titres may indicate an impaired immune response. Thus perinatal or childhood subclinical viral infections of the central nervous system, particularly of mumps, might lead to a range of possible psychiatric outcomes in later life.

Adolescent↗

Serum and CSF antibody titres to seven common viruses in schizophrenic patients.

CSF and matched serum antibody titres to seven common viruses were measured in 20 chronic schizophrenic patients, and 17 of these were age and sex-matched with orthopaedic controls. CT scans were carried out in patients and age and sex-matched radiological controls. There was a trend for CSF viral antibody titres (except CMV, HSV and VZV) to be decreased in the patients compared to controls, statistically significant for mumps and IgG. The CSF/serum ratios showed a reduction in the patients, compared to controls, statistically significant for measles and rubella as well as mumps and IgG. Cerebral ventricular size was significantly increased in the patients compared to controls, but did not correlate with any of the antibody data. These findings suggest that there is a reduced immune response to certain common viruses in the CNS of schizophrenic patients, but possible effects of institutionalisation or current medication could only be adequately excluded by further prospective studies.

Adult↗

Environmental experience produces qualitative changes in the stimulant effects of beta-phenylethylamine in rats.

The effects of beta-phenylethylamine (PEA 6.25, 12.5, and 25.0 mg/kg IP) on spontaneous motor activity were examined in rats before (novel situation) and after (familiar situation) they had experience of the test environment, in an undrugged state. In a novel cage, 12.5 mg/kg PEA stimulated rearing and locomotion. A dose of 25.0 mg/kg PEA also increased rearing and produced stereotyped head movements, but did not increase locomotion, in a novel environment. In a familiar cage, both 12.5 and 25.0 mg/kg PEA stimulated locomotion and sniffing, whereas rearing was unaffected by PEA treatment under these conditions. These data provide a striking instance of a qualitative change in the behavioural response to a psychostimulant compound which is associated with the relative familiarity of the animal with the test environment. In addition, the results show that PEA induces stereotypy at high doses and increases locomotor activity at moderate doses, which is a further illustration of the similarity in the unconditioned behavioural effects of PEA and amphetamine.

Animals↗

Naloxone suppresses fluid consumption in tests of choice between sodium chloride solutions and water in male and female water-deprived rats.

The effects of naloxone on fluid consumption by water-deprived rats trained to choose between a saline solution and water in a 15-min drinking test were examined. Rats of each sex were allocated to three groups and given access to 0.125% NaCl, 0.6% NaCl, and 1.7% NaCl, respectively, as the alternative to water. Under control conditions they drank substantially more of the hypotonic salt solutions than water, but drank slightly more water than hypertonic salt solution. Naloxone generally reduced fluid consumption, dose-dependently (0.01-10 mg/kg). In the cases of the two hypotonic solutions, the suppressant effect of naloxone was limited to saline solution. The usually low levels of water consumption were unaffected. In the case of the hypertonic solution, naloxone suppressed salt and water intakes by equivalent amounts. The effects of naloxone in the tests with the two higher salt concentrations depended upon sex. There was on example of a significant naloxone-induced reduction in saline preference (females; 0.125% NaCl v H2O). In other instances, saline preferences were not significantly modified. The results are briefly discussed in relation to current suggestions that naloxone may affect fluid consumption in ways which are taste-dependent (e.g., taste sensitivity, palatability, reward). An alternative view is also considered, that the effects of naloxone may be taste-independent, at least in the particular case of drinking in a two-choice test with saline and water.

Animals↗

Neurotransmitter receptors and monoamine metabolites in the brains of patients with Alzheimer-type dementia and depression, and suicides.

In patients with Alzheimer-type dementia, in addition to the well-known losses of cholinergic neurones, there is evidence of degeneration of the noradrenergic and serotonergic innervation of the cerebral cortex. While noradrenergic and cholinergic receptors are preserved there is a loss of serotonin S1 and S2 receptors, particularly in the temporal lobe. The loss of serotonin S2 receptors may occur at an early stage of the disease and, in temporal and frontal cortex, is correlated with the loss of somatostatin immunoreactivity. In patients dying in hospital with depression, and in individuals committing suicide, there are no consistent changes in monoamine metabolites. Noradrenergic, serotonergic, and other neurotransmitter receptors were found to be unchanged, although there was a moderate decrease in imipramine binding in a small group (n = 6) of subjects with a history of depression, who had committed suicide.

Aged↗

Potentiation of total horizontal activity and ambulation in rats treated with combinations of beta-phenylethylamine and naloxone.

The effects of beta-phenylethylamine (PEA) (6.25-50 mg kg-1) and of naloxone (1-10 mg kg-1), administered alone and in combination, were studied in the rat. Adult, male rats were individually tested in a novel enclosure over a 30 min period, after administration of drugs. Measures of total horizontal activity, ambulation and rearing activity were counted automatically on the basis of interruptions of photobeams. In addition, observational data were collected, using behavioural categories which have previously been used to characterize the behavioural stereotypy syndrome induced by phenylethylamine in large doses. The results showed that certain combinations of phenylethylamine and naloxone produced striking increases in total horizontal activity and ambulation scores, but not in vertical activity scores. Furthermore, naloxone antagonized hyperreactivity and splayed-hindlimb components of the stereotypy syndrome induced by phenylethylamine, but not the head-weaving component. The behavioural specificity of the potentiation of total horizontal activity and ambulation by phenylethylamine in combination with naloxone is emphasized, and the enhancement of activity is contrasted with previous reports of the effects of naloxone administered in conjunction with d-amphetamine.

Amphetamine↗

Microstructural analysis of chlordiazepoxide's effects on food preference behavior in roman high-, control- and low-avoidance rats.

The effects of chlordiazepoxide (CDP) on feeding performance and on rearing activity were investigated using a food preference test in three Roman strains: Roman Low Avoidance (RLA), Roman Control Avoidance (RCA), and Roman High Avoidance (RHA). The aims of the study were to assess the responses of the three strains to a free choice of familiar and novel foods following a period of food deprivation, and to answer the important psychopharmacogenetic question of whether or not the strains would display differential responsivity to CDP challenges. No strain differences were discovered in relation to the latency to begin feeding, the response to familiar food, or the frequency of rearing in the 10 min food preference test. However, clear differences did emerge in relation to the animals' responses to novel foods. In contrast to the RCA and RHA lines, RLA rats sampled a greater variety of the available foodstuffs, and devoted a greater duration to the consumption of novel foods. Despite previous reports that under conditions of mild stress, RLA animals display greater emotionality, there was no evidence from the present study to show that RLA animals were more neophobic (a possible index of emotionality) than the other two Roman lines. Indeed, the evidence clearly suggests that RLA animals may under certain circumstances pay greater attention to novel cues. CDP treatments produced reductions in rearing, reductions in eating latency, and strongly potentiated the time devoted to feeding. Effects of CDP treatments on familiar and novel foods were dissociable. CDP at 10 mg/kg reliably increased the novel food feeding duration, an effect occurring mainly within the first 5 min of the test.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cellular immune responses during complicated and uncomplicated measles virus infections of man.

Lymphocytes from patients with measles showed profound and prolonged suppression of proliferative responses to mitogens. The degree of suppression was similar in patients with uncomplicated measles virus infection and in those with pneumonia or postinfectious encephalitis. Despite this suppression, lymphocyte responses to measles antigen and PPD were demonstrated in patients with encephalitis and uncomplicated disease, even early in infection. Most patients with pneumonia did not have demonstrable antigen-specific responses. The proportions of T helper (OKT 4) and T suppressor (OKT 8) cells and functional tests of Con A suppressor cell activity showed no significant difference between control and measles patients but, in contrast to controls, cells from measles patients cultured in the absence of any stimulant significantly suppressed the proliferation of allogeneic responder cells. Nine of 20 supernatant fluids from these cultures possessed a soluble suppressor factor. These studies indicate varied disruptions of immune reactivity during measles.

Adolescent↗

Enhancement of saline consumption by chlordiazepoxide in thirsty rats: antagonism by Ro15-1788.

Water-deprived rats were given access to either water or a highly preferred 0.9% NaCl solution in a 30 min drinking test. The animals consumed substantially more saline than water. Chlordiazepoxide (2.5-20.0 mg/kg) was administered IP before the drinking test. Analysis of the results revealed a significant drug treatment X fluid condition interaction. Chlordiazepoxide produced a preferential enhancement of saline intake, achieving a peak effect at 5.0 mg/kg. Consideration of the time-course of drinking showed some complexity in the way in which chlordiazepoxide affected the saline drinking. During the first 6 min of the drinking period, the drug treatments tended to depress consumption, reaching a significant effect at 20.0 mg/kg. However, in the following 16 min interval of the drinking test, chlordiazepoxide significantly elevated saline consumption. The mechanism for this second effect may have been a retardation in the development of satiety. Finally, at the end of the drinking test, when saline consumption had become satiated, chlordiazepoxide exerted no discernible effect. The enhancement of saline consumption by chlordiazepoxide appears to have been benzodiazepine-receptor mediated, since the effect was reversed by treatment with Ro15-1788, a benzodiazepine receptor antagonist. The implications of a benzodiazepine-induced increase in salt intake are briefly considered. The over consumption of salt is contraindicated in certain clinical conditions. Both stress and hypertension are associated with elevated salt appetite. Treatment of these conditions using benzodiazepines may require due consideration of the possible stimulant effect of these drugs on salt appetite.

Animals↗

Hypodipsia, stereotypy and hyperactivity induced by beta-phenylethylamine in the water-deprived rat.

beta-Phenylethylamine (PEA) is an endogenous constituent of human, rat and other mammalian brain tissue. It is rapidly metabolised by type B monoamine oxidase, and there is evidence for specific binding sites for PEA in rat brain. In the first experiment, the effects of systemically-administered PEA (3.125-50.0 mg/kg) on water consumption in water deprived male rats were investigated. PEA produced a depression of drinking within the first 15 min following its administration, with a strong linear relation between drug dose and the degree of depression. In the following 45 min, there was evidence of a dose-related recovery in the drinking. In the second experiment, the effects of PEA on activity in water-deprived rats were investigated. PEA at 12.5 m/kg produced behavioral stimulation, which was particularly evident in measures of total horizontal activity. At higher doses, 25.0 and 50.0 mg/kg, PEA induced a behavioral stereotypy syndrome, associated with a depression of horizontal and vertical activities. Relationships between the hypodipsic effect of PEA and its ability to produce psychomotor stimulation at a moderate dose level, and stereotypy at higher dose levels are considered.

Animals↗

Effects of a kappa receptor agonist, ethylketocyclazocine, on water consumption in water-deprived and nondeprived rats in diurnal and nocturnal tests.

In 24 hr water-deprived male hooded rats, ethylketocyclazocine (EKC), 0.1-3.0 mg/kg, dose-dependently suppressed water intake. Within the first 30 min access to water, drinking was virtually abolished by 1.0 and 3.0 mg/kg EKC. Significant reductions in the level of water intake were found after 0.1 mg/kg EKC. After 2 hr access to water, the suppressant effect was attenuated indicating some recovery. The antidipsogenic action of EKC in water-deprived rats was comparable in its effect for both daytime and nocturnal testing. Circadian variation may not be an important modulator of the antidipsogenic action. Naloxone, an opiate receptor antagonist, when administered in a dose of 0.3 mg/kg also significantly reduced drinking in deprived animals. EKC (0.3 mg/kg) and naloxone (0.3 mg/kg) when administered together displayed mutual antagonism. Drinking was at control levels. In nondeprived male rats, EKC exerted some dipsogenic action, most noticeably during diurnal testing. Within 30 min access to water, 0.1 mg/kg EKC significantly elevated the level of water intake. This effect did not occur during nocturnal testing, when the only immediate effect of EKC was a suppression of drinking at 1.0 and 3.0 mg/kg dose levels. After 2 hr access to water, there was a significant peak effect to enhance drinking at the 0.3 mg/kg dose level during the daytime. Effects of EKC during the night were less pronounced. The dipsogenic action of EKC (0.3 and 1.0 mg/kg) in satiated animals during the day was abolished by naloxone and Mr-2266BS, also an opiate receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of piribedil and of d-amphetamine on locomotor activity in immature rats.

The effects of piribedil, a direct dopamine (DA) agonist, and of d-amphetamine, an indirect DA agonist, on locomotor activity in 28-day old rats have been investigated. d-Amphetamine (1,2 and 4 mg/kg) increased activity in a dose dependent manner whereas only a 40 mg/kg dose of piribedil significantly increased activity; low doses of piribedil (1.25-10.0 mg/kg) had no effect on activity. Since hyperactivity induced by a direct DA agonist, such as piribedil, is thought to reflect post-synaptic DA receptor activation, the results appear to indicate that post-synaptic DA receptor mechanisms are fully developed in 28-day old rats. In contrast, as low doses of piribedil which cause sedation in adult animals failed to decrease locomotor activity under the present experimental conditions, it seems that DA autoreceptors may not be well developed in 28-day old rats.

Aging↗

Pharmacodynamics and pharmacokinetics of digoxin in the presence of lithium.

Previous biochemical and clinical data suggest there may be an interaction between digoxin and lithium. The pharmacodynamics and pharmacokinetics of an intravenous infusion of digoxin were studied in six male subjects before and after 2 weeks treatment with lithium carbonate. The effects of lithium on sodium pump activity, intracellular electrolytes and extracellular electrolytes were studied. No significant interaction between digoxin and lithium was found. No significant effects of lithium on sodium pump activity or electrolyte concentrations were found.

Adolescent↗