Biomedical subjects

T C Kirkham

Publications and source records attributed to T C Kirkham.

25 records · Page 2Linked to original sources

PubMed1987

The pyrazoloquinoline, CGS 8216, reduces sham feeding in the rat.

The pyrazoloquinoline CGS 8216, a benzodiazepine receptor ligand, produced a dose-related (2.5-10.0 mg/kg, IP) attenuation of sham feeding a 30% sucrose solution by rats with open gastric fistulas. Ingestion was reduced by over 50% following the largest dose of CGS 8216 in a 60 min test. The initiation of sham feeding was not delayed by CGS 8216, but sham feeding was subsequently slowed over an extended test period. The suppressant effect of CGS 8216 was reversed by the specific benzodiazepine receptor antagonist Ro15-1788 (20 and 40 mg/kg, IP). Hence the effect of CGS 8216 on sham feeding may be mediated by benzodiazepine receptors, and is consistent therefore with the characterization of CGS 8216 as a benzodiazepine partial inverse agonist. In contrast to sham feeding, CGS 8216 (10.0 mg/kg, IP) did not affect sham drinking in 17 hr water-deprived rats. The results are discussed in relation to possible benzodiazepine receptor involvement in the neurochemical mediation of food palatability.

Animals↗

PubMed1987

Effects of naloxone and naltrexone on meal patterns of freely-feeding rats.

The effects of naloxone and naltrexone on the night-time meal patterning of freely-feeding male rats were investigated using a Kissileff-type eatometer. Naloxone (5.0 mg/kg) and naltrexone (2.5 mg/kg) reduced intake for two hours after IP injection. This effect resulted from a shortening of duration of meals and an extension of postmeal intervals. Unlike other anorexic agents neither drug affected meal frequency or the eating rate within meals. These particular opioid antagonists therefore appear to produce anorexia by advancing meal termination and extending the inhibition of feeding which follows a meal. These specific changes in the structure of the meal pattern consolidate previous findings and support the hypothesis that naloxone and naltrexone reduce food intake in rats by promoting satiation and prolonging satiety.

Animals↗

PubMed1987

Differential effects of CGS 8216 and naltrexone on ingestional behaviour.

Effects of the pyrazoloquinoline CGS 8216 (a partial benzodiazepine receptor inverse agonist) and the opiate antagonist, naltrexone, were compared in several tests of ingestion in non-deprived and deprived male rats. Both naltrexone (0.1-10.0 mg/kg, SC) and CGS 8216 (1.25-10.0 mg/kg, IP) significantly reduced the consumption of a highly palatable saccharin-glucose solution by non-deprived rats. Both compounds were also effective in reducing, dose-dependently, the intake of palatable sweet or oily mash by non-deprived animals. Hence, naltrexone and CGS 8216 attenuated palatability-induced ingestional responses, and sweet taste was not necessary for this effect to occur. The two drugs also reduced the intake of the saccharin-glucose solution in food-deprived rats, but their effects diverged in water-deprived animals. CGS 8216 had relatively little effect in the thirsty animals, whereas the effect of naltrexone was enhanced. This difference was underscored in a final test of deprivation-induced consumption of water. Naltrexone reduced the drinking, but CGS 8216 had no effect. Taken together, these data indicate that CGS 8216 was more selective in its effects on ingestion.

Animals↗

PubMed1986

CGS 8216, a novel anorectic agent, selectively reduces saccharin solution consumption in the rat.

The pyrazoloquinoline CGS 8216, a high-affinity ligand for benzodiazepine recognition sites, significantly reduced the consumption of a preferred 0.05% sodium saccharin solution in a 30 min two-bottle test. A highly significant effect was detected at 5.0 mg/kg, IP and at higher doses. The consumption of water and 0.6% saline, in two-bottle tests, or of quinine solution and water, in a forced-choice test, was not reliably affected by CGS 8216. The results point to a sensitive and selective intrinsic effect of CGS 8216 on ingestional responses in the rat.

Animals↗

PubMed1986

Effect of naloxone and naltrexone on the development of satiation measured in the runway: comparisons with d-amphetamine and d-fenfluramine.

A straight runway was used to monitor changes in measures of food motivation and food consumption in order to track and to characterise the development of satiation following administration of equianorectic doses of naloxone (5.0 mgkg-1), naltrexone (2.5 mgkg-1), dexfenfluramine (1.5 mgkg-1) and d-amphetamine (1.0 mgkg-1). Naloxone and naltrexone did not reduce motivational measures or block food consumption during the early trials. These drugs brought about a prompt cessation of intake only after some food had been consumed. Dexfenfluramine displayed an early effect on motivation and hastened the onset of satiation. The anorexic activity of d-amphetamine was virtually abolished. These results indicate that the runway is a useful device for analysing the effects of drugs on eating motivation. This study has further characterised the anorexic actions of naloxone and naltrexone; the profiles of these agents can be distinguished from both dexfenfluramine and d-amphetamine. The suppressive action on food intake exerted by these particular opioid antagonists appears to arise from an intensification of the feedback from food ingestion. The mechanisms through which this effect is achieved are not known.

Animals↗

PubMed1985

Endorphins and food intake: kappa opioid receptor agonists and hyperphagia.

Evidence from studies which utilise either opiate receptor agonists and antagonists strongly indicate a role for endorphinergic mechanisms in the control of feeding responses. Two means by which these compounds may exert an effect on feeding can be singled-out. Firstly, emerging evidence suggests that the process of achieving satiety (terminating a meal, or choice of a commodity) may be accelerated following treatments with opiate receptor antagonists. Secondly, the preference for highly palatable solutions (sweet solutions have received most attention) in two-bottle tests is blocked after injection of opiate receptor antagonists. This finding has been interpreted in terms of the abolition of the reward or incentive quality associated with the particularly attractive flavour. These two mechanisms of action may represent two aspects of a single, fundamental process. Following an introduction to rat urination model of in vivo kappa agonist activity, the consistent effect of several kappa agonists (including the highly selective U-50,488H) to stimulate food consumption is described. Recognising that members of the dynorphin group of endogenous opioid peptides are kappa receptor ligands, some with a high degree of selectivity, and the evidence the dynorphins and neo-endorphins produce hyperphagia in rats is particularly interesting. Such lines of evidence lead to the hypothesis that peptides of the dynorphin group may act endogenously to promote the expression of normal feeding behaviour.

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

PubMed1984

Dual action of naloxone on feeding revealed by behavioural analysis: separate effects on initiation and termination of eating.

In two experiments observational analyses have been made of eating and other behaviours following naloxone administration. Naloxone produced a clearly defined profile of behavioural changes. Although rats became became more inactive it was demonstrated that this was not responsible for the inhibition of food intake. The drug reduced the latency to approach food and to initiate eating bouts. In addition, naloxone hastened the termination of eating in the test period. Therefore naloxone simultaneously increases one aspect of motivation for food, yet also promotes the onset of satiation. This profile of naloxone's anorexic action is quite different to that of traditional anorexic drugs such as amphetamine of fenfluramine. This dual action of naloxone, disclosed by these studies, may account for certain curious features of naloxone's effect on food intake.

Animals↗