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Discriminative stimulus effects of gamma-hydroxybutyrate (GHB) and its metabolic precursor, gamma-butyrolactone (GBL) in rats.

Baker LE, Van Tilburg TJ, Brandt AE, Poling A

Department of Psychology, Western Michigan University, Kalamazoo, MI 49008, USA. lisa.baker@wmich.edu

RATIONALE: Gamma-hydroxybutyrate (GHB) is becoming an increasingly popular drug of abuse. Metabolic precursors of GHB, gamma-butyrolactone (GBL) and 1,4-butanediol (BDL), are commercially available industrial solvents that may also present potential health risks. Relatively little is known about the neurobehavioral effects of GHB and its precursors. OBJECTIVE: The aim of the present investigation was to characterize the discriminative stimulus effects of GHB and its precursor, GBL. METHODS: Male Sprague-Dawley rats were trained to discriminate GHB [300 mg/kg, i.g.; n=16] or GBL (150 mg/kg, i.p.; n=8) from vehicle under a fixed ratio 20 (FR 20) schedule of food reinforcement. Stimulus generalization tests were then conducted with several compounds. RESULTS: GHB and GBL produced cross-generalization and BDL was fully substituted for both GHB and GBL. Two benzodiazepines, alprazolam and diazepam, and the 5-HT1A agonist, buspirone, did not substitute for either training drug nor did ethanol or the NMDA antagonists, PCP and ketamine. The GHB antagonist, NCS-382, and the GABA(B) antagonist, CGP-35348, blocked the discriminative stimulus effects of GHB but not those of GBL. CONCLUSIONS: These findings suggest that GHB and its metabolic precursors produce similar subjective effects that differ from those of other sedative-hypnotic drugs. Further investigations into the neurochemical actions underlying the subjective effects of these drugs are warranted.

Published 21 October 2005 in Psychopharmacology (Berl), 181(3): 458-66.
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