Benzodiazepine-induced hyperphagia in the nondeprived rat: comparisons with CL 218,872, zopiclone, tracazolate and phenobarbital.
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.
Cooper
S J
SJ
Moores
W R
WR
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds; D001569:Benzodiazepines; D005247:Feeding Behavior / Q000187:drug effects*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats
D014151:Anti-Anxiety Agents; D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; D011720:Pyrazoles; D011724:Pyridazines; C515050:zopiclone; D001569:Benzodiazepines; C021604:CL 218872; C034317:tracazolate; D010634:Phenobarbital