Chlordiazepoxide-induced hyperphagia in rats: lack of effect of GABA agonists and antagonists

Because of the evidence that benzodiazepine binding sites are associated with GABA receptors in the central nervous system, it has been suggested that the behavioural effects of benzodiazepines may be mediated by GABAergic mechanisms. In order to investigate this hypothesis in relation to the hyperphagia produced by benzodiazepines, the effects of chlordiazepoxide were compared with those of the GABA agonists progabide and muscimol and the GABA antagonists picrotoxin and bicuculline. In rats adapted to a 22 h/day food deprivation schedule chlordiazepoxide produced a dose-related increase in food intake. Neither progabide nor muscimol produced a similar effect after IP injection, nor did these drugs potentiate the effects of a dose of chlordiazepoxide. Picrotoxin and bicuculline, each given at a sub-convulsant dose, did not affect quantities of food consumed and also did not antagonise the effect of chlordiazepoxide. These results provide no evidence for the hypothesis that chlordiazepoxide-induced hyperphagia in rats is mediated by GABAergic mechanisms.