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Biomedical subjects

S J Cooper

Publications and source records attributed to S J Cooper.

At least 109 records · Page 6Linked to original sources
PubMed1989

Opposite effects of SK&F 38393, a dopamine D-1 agonist, and SCH 23390, a dopamine D-1 antagonist, in tests of salt preference/aversion in the rehydrating rat.

Male rats were adapted to a 22-hr water-deprivation schedule, and to a 15-min choice test, in which water was available in one drinking tube, and water, 0.064%, 0.16%, 0.4%, 1.0%, or 2.5% NaCl solution, respectively, was available in a second. A typical saline preference-aversion function was obtained. The selective dopamine D-1 agonist, SK&F 38393 (3.0 mg/kg, IP), significantly depressed choice of hypertonic saline solutions (1.0% and 2.5% NaCl solutions), without affecting preference for hypotonic saline solutions. In contrast, the selective dopamine D-1 antagonist, SCH 23390 (0.1 mg/kg, SC), significantly increased the preference measure in the case of hypertonic solutions. These data indicate a role for D-1 receptors in dopaminergic mediation of the descending limb of the saline preference-aversion function.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Sucrose sham-feeding in the rat after administration of the selective dopamine D2 receptor agonist N-0437, d-amphetamine or cocaine.

Drugs which act as agonists at dopamine receptors, or which increase dopamine release (e.g., d-amphetamine, cocaine) are known to reduce food intake. The present experiments investigated, for the first time, the effects of a highly selective dopamine D2 receptor agonist, N-0437 (0.3-3.0 mg/kg, IP), on 5% sucrose sham-feeding in gastric fistulated rats, and compared these results with those of d-amphetamine (0.1-3.0 mg/kg, IP) and cocaine (3.0-10.0 mg/kg, IP). The results showed that sucrose sham-feeding was resistant to the effects of N-0437, even though the D2 agonist dose-relatedly reduced sucrose real-feeding in intact animals. The two psychomotor stimulants, d-amphetamine and cocaine, produced some reductions in sham-feeding, although in the case of the highest dose of d-amphetamine, the pronounced reduction in the consumption of sucrose was probably secondary to induced behavioral stereotypy. The results suggest that D2 receptor stimulation may interact with satiety cues to reduce ingestion of sucrose, but that in the absence of potent satiety stimuli D2 receptor stimulation is ineffective. Furthermore, N-0437 appeared not to be equivalent to either d-amphetamine or cocaine in their effects to reduce sucrose sham-feeding.

Animals↗
PubMed1989

The selective dopamine D1 receptor agonist SK&F 38393: its effects on palatability- and deprivation-induced feeding, and operant responding for food.

A series of experiments investigated the involvement of the dopamine D1 receptor subtype in relation to feeding responses. The selective D1 agonists, SK&F 38393 (1.0-20 mg/kg) and SK&F 75760 (5 mg/kg), significantly reduced palatable food consumption in nondeprived rats. The anorectic effect of SK&F 38393 (10 mg/kg) was additive with that of the selective D2 receptor agonist, N-0437 (0.3 mg/kg). In nondeprived mice, SK&F 38393 had a stereoselective effect to reduce palatable food intake. At a peripherally-selective dose (3.0 mg/kg), the peripheral dopamine D1 receptor agonist, fenoldopam, had no effect on food intake. At 10 mg/kg, however, it exhibited anorectic properties, although this may have been due to some penetration of the blood-brain barrier. In rats adapted to a food-deprivation schedule, SK&F 38393 (3.0-30 mg/kg) produced significant dose-dependent reductions in consumption of powdered chow and in lever-pressing for food pellets on a FR8 schedule of reinforcement. In rats adapted to a water-deprivation schedule, SK&F 38393 (3.0-30 mg/kg) was substantially less effective in reducing water intake. The results are discussed in terms of a possible selective effect of D1 agonist activity on feeding behaviour.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Pharmacological manipulations of sucrose consumption in the Syrian hamster.

Nondeprived, male Syrian hamsters (Mesocricetus auratus) were adapted to a daily schedule of 2-hr access to a 10% sucrose solution. Two benzodiazepines, midazolam (1.0-10 mg/kg) and flurazepam (1.0-10 mg/kg), produced dose-dependent increases in sucrose consumption. In contrast, the alpha 2-adrenergic agonist, clonidine (0.01-0.3 mg/kg), had no effect on sucrose intake. Neither d-fenfluramine nor d-amphetamine affected sucrose ingestion in the hamsters, except at a large dose (10 mg/kg). Nevertheless, significant, dose-dependent reductions in sucrose consumption were observed after the administration of either opiate antagonists (naltrexone; nalmefene) or selective dopamine D2 receptor agonists (N-0437; quinpirole). The results are compared and contrasted with previously reported data for rats.

Amphetamine↗
PubMed1989

Effects of naltrexone on food preference and concurrent behavioral responses in food-deprived rats.

Naltrexone (0.05-5.0 mg/kg, SC) was administered to food-deprived rats prior to a 15-min food-preference test. Total food intake and feeding duration was reduced following administration of the opiate antagonist. However, while naltrexone reduced the consumption of the initially-preferred chocolate-coated cookies, the ingestion of the nonpreferred standard laboratory chow pellets was significantly enhanced. These data cannot be explained in terms of a general anorexic effect and nonspecific suppression of feeding responses. Instead, they indicate that naltrexone reduced preference for the highly palatable cookies, so that a feeding response to the chow pellets emerged. Under the conditions of test-familiarity, naltrexone did not reduce grooming, locomotion or rearing duration. An increase in locomotion may have been secondary to the reduction in feeding. The results agree with previous data from animal and human studies in suggesting that endogenous opioid peptide activity is involved in the palatability of preferred foods.

Animals↗
PubMed1989

Stimulation and inhibition of food intake by the selective dopamine D2 agonist, N-0437: a meal pattern analysis.

Feeding and drinking responses were recorded in home-caged rats over 24-hour periods, and the data were analysed in terms of meal patterns. The highly selective dopamine D2 receptor agonist, N-0437, was injected IP at the start of the night phase. At the smallest dose (0.3 mg/kg), N-0437 increased food intake as a result of increases in meal size and duration. The rate of feeding during meals was not increased. This effect lasted 1-2 hours in the night phase. At higher doses (1.0 and 3.0 mg/kg), N-0437 inhibited food intake for 3-6 hours. The inhibition was due to a substantial reduction in meal size, with no change in meal frequency. Rate of feeding during meals tended to be reduced. A biphasic dose-effect relationship was not apparent in the drinking data, and there was not a significant effect of N-0437 on drinking responses. The meal pattern analysis results indicate the stimulation of D2 receptors produces increases and decreases in food intake and meal size. These results are discussed in terms of dose-dependent stimulation of presynaptic (autoreceptor) and postsynaptic D2 receptors, and the relationship to satiety within meals.

Animals↗
PubMed1989

Novel benzodiazepine receptor ligands: palatable food intake following zolpidem, CGS 17867A, or Ro23-0364, in the rat.

The potent imidazopyridine hypnotic, zolpidem, binds to central benzodiazepine receptors and has predominantly sedative properties, as determine in animal models. In tests of palatable food consumption in nondeprived male rats, the present results indicate that zolpidem (0.3-3.0 mg/kg) had no effect on food intake. Its lack of effect contrasts sharply with other benzodiazepine agonists which strongly stimulate palatable food intake. Two other novel compounds, both of which bind to benzodiazepine receptors, and which have reduced propensity to induce sedative effects, increased palatable food consumption, although in differing ways. The imidazobenzodiazepine Ro23-0364 (0.3-10.0 mg/kg) dose-dependently increased feeding in the standard procedure, but failed to stimulate food intake in presatiated animals. The pyrazoloquinoline CGS 17867A (1.0-30.0 mg/kg) increased food intake in both test procedures, although the dose-effect relationship was nonmonotonic. Taken together, the data indicate a probable separation between hyperphagic and sedating effects of benzodiazepine receptor agonists. If zolpidem's sedative effect is linked to an action at a receptor subtype (benzodiazepine Type 1 or omega 1), then the hyperphagic effect of benzodiazepines may depend more on the alternative subtype.

Animals↗
PubMed1989

Tardive dystonia. The benefits of time.

Tardive dystonia is a rare movement disorder. We outline the development of tardive dystonia in a young schizophrenic, and demonstrate the importance of applying a double-blind, placebo-controlled, cross-over trial of any putative successful treatment.

Adult↗
PubMed1988

Clonazepam selectively increases saccharin ingestion in a two-choice test.

Twenty-two-hour water-deprived rats were trained with a choice between a sodium saccharin solution (0.01% or 0.05%) and water in a 30-min drinking test. The potent benzodiazepine agonist, clonazepam, produced highly significant dose-related (0.1-1.0 mg/kg, i.p.) increases in total fluid consumption. The most important finding was that clonazepam selectively enhanced ingestion of the preferred 0.05% solution, while producing no change in the consumption of water. It did not selectively affect ingestion of the marginally preferred 0.01% solution. These data can be linked to recent evidence that benzodiazepines facilitate positive ingestive reactions elicited by palatable tastes. Together, the evidence indicates that benzodiazepines can selectively affect consumption of preferred solutions through enhancement of positive reactions to palatable tastes. In contrast to the results with clonazepam, the novel compound zolpidem, which binds preferentially to cerebellar-type benzodiazepine sites, failed to affect fluid intake or sweet taste preference. This suggests that hippocampal-type, as distinct from cerebellar-type receptors, may be necessary in the mediation of effects of benzodiazepines on taste-palatability processing and ingestion.

Administration, Oral↗
PubMed1988

MDL 72832, a selective 5-HT1A receptor ligand, stereospecifically increases food intake.

Effects of the enantiomers of MDL 72832, a novel, potent and selective ligand for 5-HT1A sites, were investigated in a test of platable food consumption in partially pre-satiated male rats. (-)-MDL 72832 significantly increased feeding at 0.03 mg/kg s.c., whereas 1.0 mg/kg (+)-MDL 72832 was required to stimulate food intake. The stereospecificity of the effect provides support for a functional role of 5-HT1A receptors in feeding responses.

Animals↗
PubMed1988

Observational analysis of the effects of kappa opioid agonists an open field behaviour in the rat.

An observational analysis of the effects of four kappa-opioid agonists on forward locomotion, rearing and grooming displayed by rats in a novel open field was undertaken. The doses of agonists used corresponded to those previously found to produce changes in food consumption. Ethylketocyclazocine (0.1 and 1 mg/kg), bremazocine (0.01 and 0.1 mg/kg) and tifluadom (0.3 and 3 mg/kg) exerted suppressant effects on all the activities monitored. Grooming behaviour appeared to be particularly sensitive to this action, being virtually abolished by the larger doses of these compounds. In contrast, the selective kappa agonist U-50,488H (0.1-3 mg/kg) only attenuated grooming at the two highest doses tested (1 and 3 mg/kg). None of the agonists tested produced stimulation of open field activity during the 1-h study. Reductions in activity occurred at doses previously found to increase and decrease food intake. It was therefore concluded that the hyperphagia induced by kappa agonists was not part of a more general behavioural activation, whilst reductions in food consumption probably result from a non-specific behavioural depression.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1988

The 5-HT1A agonist 8-OH-DPAT increases consumption of palatable wet mash and liquid diets in the rat.

The 5-HT1A agonist 8-OH-DPAT, at a dose of 30 micrograms/kg, enhanced the consumption of sweetened wet mash and sweetened milk in non-deprived rats. In partially satiated rats, sensitivity to the hyperphagic effect of 8-OH-DPAT on wet mash intake was substantially increased, so that the minimally effective dose was reduced to 3 micrograms/kg. Similarly, 8-OH-DPAT was more efficacious in increasing milk intake in satiated rats. Thus, 30 and 40 micrograms/kg 8-OH-DPAT produced a 4-fold increase of milk intake in completely satiated rats compared to a 2-fold increase in partially satiated animals at a dose of 30 micrograms/kg. The increased intake of liquid and wet mash diets observed after treatment with low doses of 8-OH-DPAT argues against the involvement of non-specific gnawing in the increased consumption of solid food produced by the drug. Rather, the data suggest that 8-OH-DPAT may specifically stimulate appetite by counteracting a tonic serotonergic inhibition of feeding. The present experiments also showed that 8-OH-DPAT attenuates fenfluramine-induced anorexia which is thought to depend on increased serotonergic neurotransmission.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

Bi-directional changes in sham feeding in the rat produced by benzodiazepine receptor ligands.

Both the real and sham intake of a 5% sucrose solution were increased by midazolam (3 mg/kg IP), a benzodiazepine agonist. In contrast, both the real and sham intakes of a 20% sucrose solution were reduced by Ro15-3505 (a benzodiazepine antagonist with weak inverse agonist properties) and by FG 7142 (a beta-carboline inverse agonist). These data demonstrate that drugs acting at benzodiazepine receptors can bi-directionally alter ingestional responses, probably by modulation of the oropharyngeal control of consumption.

Animals↗
PubMed1988

Specific effect of putative 5-HT1A agonists, 8-OH-DPAT and gepirone, to increase hypertonic saline consumption in the rat: evidence against a general hyperdipsic action.

Previous reports indicate that 5-HT1A agonists, in addition to benzodiazepines, increase the consumption of hypertonic saline in rehydrating rats. Experiment 1 investigated the effects of 8-OH-DPAT (10-100 micrograms/kg) and gepirone (0.1-3.0 mg/kg) on consumption of water and of saline over a range of concentrations (0.45%-2.8%) in a 30 min drinking test. The two 5-HT1A agonists dose-dependently increased ingestion of two hypertonic salt solutions, but produced little or no increase in the drinking of water, hypotonic or isotonic saline. Experiment 2 demonstrated that 8-OH-DPAT and gepirone did not enhance water consumption in animals given a water preload, or markedly increase drinking quinine-adulterated water. Taken together, the results indicate a selective dose-related effect of the two drugs to increase hypertonic saline drinking; they did not have a general hyperdipsic effect across all salt and water conditions, and they did not increase intake simply because of a low baseline level of consumption. Hence, 5-HT1A agonist act much more selectively than benzodiazepines in their effects on drinking responses.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

Evidence for serotonergic modulation of sucrose sham-feeding in the gastric-fistulated rat.

Both the real and sham intakes of a 5% sucrose solution were reduced by d-fenfluramine, quipazine (a 5-HT receptor agonist), and fluoxetine (a selective 5-HT reuptake inhibitor). These data demonstrate a serotonergic inhibitory component in the control of sham-feeding. In support of this, 8-OH-DPAT (a selective 5-HT1A agonist), which inhibits serotonergic activity at small doses via an autoreceptor mechanism, enhanced sucrose sham-feeding and reversed the suppressant effect of d-fenfluramine. Together, the results indicate a serotonergic influence on ingestional responses which is probably closely related to the oropharyngeal control of consumption.

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