Discriminative and reinforcing effects of brotizolam in rhesus monkeys

Michael A. Nader, Gail Winger, James H. Woods, William L. Woolverton

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The reinforcing and discriminative stimulus effects of brotizolam, a benzodiazepine-hypnotic, were evaluated in rhesus monkeys. In one experiment, separate groups of monkeys (N=3/group) were trained to discriminate pentobarbital (10 mg/kg, IG) or d-amphetamine (0.56-1.0 mg/kg, IG) from saline, in a discrete-trials avoidance/escape paradigm. Pentobarbital (5.6-10 mg/kg), diazepam (1.0-1.7 mg/kg), and brotizolam (0.3-1.7 mg/kg) resulted in 100% drug-lever responding in all three pentobarbital-trained monkeys. In d-amphetamine-trained monkeys brotizolam administration resulted only in saline-lever responding. In another experiment, monkeys were surgically prepared with indwelling intravenous catheters and lever pressing resulted in an injection of 0.1 mg/kg/injection sodium methohexital under a fixed-ratio 10 (FR 10) schedule. Pentobarbital (0.01-0.3 mg/kg/injection) and diazepam (0.003-0.10 mg/kg/injection) maintained responding above saline control levels when substituted for methohexital. Brotizolam (0.001-0.01 mg/kg/injection) resulted in more injections received compared to saline, but fewer injections compared to pentobarbital or diazepam. Thus, results from the present experiment suggest that brotizolam would have pentobarbital-like subjective effects. However, the abuse liability of brotizolam may be lower than that for diazepam.

Original languageEnglish (US)
Pages (from-to)166-171
Number of pages6
JournalPsychopharmacology
Volume103
Issue number2
DOIs
StatePublished - Feb 1991

Keywords

  • Brotizolam
  • Drug discrimination
  • Pentobarbital
  • Rhesus monkeys
  • Self-administration

ASJC Scopus subject areas

  • Pharmacology

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