Behavioral effects of flunitrazepam: reinforcing and discriminative stimulus effects in rhesus monkeys and prevention of withdrawal signs in pentobarbital-dependent rats

Lisa R. Gerak, William L. Woolverton, Michael A. Nader, Graham A. Patrick, Louis S. Harris, Gail Winger, James H. Woods, Charles P. France

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Flunitrazepam was evaluated in several procedures that have been used extensively to study the behavioral effects and abuse potential of positive GABAA modulators. One group of monkeys (n=3) responded to receive injections of methohexital or saline (i.v.) while other groups (n=2-4/group) discriminated vehicle from either pentobarbital or triazolam. Other monkeys (n=2) received diazepam daily and discriminated flumazenil from vehicle. Finally, the ability of flunitrazepam to prevent the emergence of withdrawal signs in pentobarbital-treated rats was evaluated. Flunitrazepam maintained i.v. self-administration that was, on average, less than that maintained by methohexital and greater than that maintained by saline. In drug discrimination studies, flunitrazepam substituted for pentobarbital and for triazolam and failed to substitute for flumazenil. In rats (n=3-6/group), signs of withdrawal were not evident when flunitrazepam treatment replaced pentobarbital treatment; withdrawal signs emerged when either pentobarbital or flunitrazepam treatment was terminated. Taken together with data from previous studies, these data suggest that the abuse liability of flunitrazepam is comparable to that of other benzodiazepines.

Original languageEnglish (US)
Pages (from-to)39-49
Number of pages11
JournalDrug and Alcohol Dependence
Volume63
Issue number1
DOIs
StatePublished - Jun 1 2001

Keywords

  • Drug discrimination
  • Flunitrazepam
  • Pentobarbital-dependent rats
  • Rhesus monkey
  • Self-administration

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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