Nondeprived male rats were familiarized with 30 min daily access to a highly palatable diet.
Clonazepam,
midazolam and
chlordiazepoxide each produced significant dose-dependent increases in food consumption.
Clonazepam was the most potent, and a significant hyperphagic effect was detected following 0.078 mg/kg (IP). Amongst novel non-
benzodiazepine anxiolytics,
zopiclone and
CL 218,872 also produced significant increases in food intake. The smallest doses to produce significant
hyperphagia for these two drugs were 10.0 and 2.5 mg/kg (IP) respectively. In contrast,
tracazolate caused only a reduction in feeding, evident at 20 and 40 mg/kg (IP). Previous reports indicate that although
benzodiazepines,
zopiclone and
CL 218,872 displace [3H]
flunitrazepam binding in rat cerebral cortex preparations,
tracazolate enhances the binding. Our results are consistent with the
drug-induced
hyperphagia depending upon agonist actions at high-affinity
benzodiazepine sites. They also provide pharmacological evidence for a dissociation between hyperphagic and
anxiolytic drug effects.
Phenobarbital (2.5-40.0 mg/kg), like the
benzodiazepines, produced a strong stimulation of food intake, indicating that
drug action at an alternative site in the
benzodiazepine receptor-
GABA receptor-
chloride channel complex can also lead to
hyperphagia.