Discriminative stimulus effects of gamma-hydroxybutyrate (GHB) and its metabolic precursor, gamma-butyrolactone (GBL) in rats.
BACKGROUND
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.
Department of Psychology, Western Michigan University, Kalamazoo, MI 49008, USA. lisa.baker@wmich.edu
Lisa E
LE
Baker
Timothy J
TJ
Van Tilburg
Andrew E
AE
Brandt
Alan
A
Poling
D015107:4-Butyrolactone / Q000494:pharmacology*; D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D005795:Generalization, Stimulus / Q000187:drug effects; D013287:Illicit Drugs / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000819:agonists; D010622:Phencyclidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012978:Sodium Oxybate / Q000494:pharmacology*
D013287:Illicit Drugs; D000431:Ethanol; D016202:N-Methylaspartate; D007649:Ketamine; D012978:Sodium Oxybate; D010622:Phencyclidine; D015107:4-Butyrolactone