Evaluation of the reinforcing and discriminative stimulus effects of 1,4-butanediol and γ-butyrolactone in rhesus monkeys

Lance R. McMahon, Andrew Coop, Charles P. France, Gail Winger, William L. Woolverton

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Metabolic precursors and prodrugs of γ-hydroxybutyrate (GHB), including 1,4-butanediol (BDL) and γ-butyrolactone (GBL), have sedative and anesthetic effects and might have positive reinforcing effects. BDL and GBL were evaluated using behavioral procedures that measure positive reinforcing effects and discriminative stimulus effects of drugs that modulate γ-aminobutyric acid (GABA) at the GABAA receptor complex. One group of rhesus monkeys could respond for saline or the barbiturate methohexital (i.v.) in a self-administration paradigm. Two other groups of monkeys discriminated the barbiturate pentobarbital (i.g.) or the benzodiazepine midazolam (s.c.) from saline in a drug discrimination paradigm; another group of monkeys was treated with the benzodiazepine diazepam (5.6 mg/kg/day, p.o.) and discriminated the benzodiazepine antagonist flumazenil (s.c.) from vehicle. In self-administration experiments, methohexital and not BDL (0.1-3.2 mg/kg/injection) or GBL (0.1-3.2 mg/kg/injection) reliably maintained responding above saline levels. BDL and GBL, up to doses that suppressed responding, did not substitute for pentobarbital, midazolam or flumazenil. The onset of action for both drugs to decrease response rate was delayed (90 min for GBL and 150 min for BDL). These results suggest that any abuse-related effects of BDL and GBL are qualitatively different from the abuse-related effects of GABAA receptor modulators and further indicate that BDL and GBL do not have positive reinforcing effects in rhesus monkeys experienced with self-administration of a short-acting sedative-hypnotic.

Original languageEnglish (US)
Pages (from-to)113-120
Number of pages8
JournalEuropean Journal of Pharmacology
Volume466
Issue number1-2
DOIs
StatePublished - Apr 11 2003

Keywords

  • 1,4-Butanediol
  • Barbiturate
  • Benzodiazepine
  • Drug discrimination
  • Self-administration
  • γ-Butyrolactone

ASJC Scopus subject areas

  • Pharmacology

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