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Benzodiazepine-induced hyperphagia in the nondeprived rat: comparisons with CL 218,872, zopiclone, tracazolate and phenobarbital.

Abstract
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.
AuthorsS J Cooper, W R Moores
JournalPharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 23 Issue 2 Pg. 169-72 (Aug 1985) ISSN: 0091-3057 [Print] United States
PMID2865747 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Anti-Anxiety Agents
  • Azabicyclo Compounds
  • Hypnotics and Sedatives
  • Piperazines
  • Pyrazoles
  • Pyridazines
  • zopiclone
  • Benzodiazepines
  • CL 218872
  • tracazolate
  • Phenobarbital
Topics
  • Animals
  • Anti-Anxiety Agents (pharmacology)
  • Azabicyclo Compounds
  • Benzodiazepines
  • Feeding Behavior (drug effects)
  • Hypnotics and Sedatives (pharmacology)
  • Male
  • Phenobarbital (pharmacology)
  • Piperazines (pharmacology)
  • Pyrazoles (pharmacology)
  • Pyridazines (pharmacology)
  • Rats

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