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.
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.
Authors: Lance R McMahon; Andrew Coop; Charles P France; Gail Winger; William L Woolverton Journal: Eur J Pharmacol Date: 2003-04-11 Impact factor: 4.432
Authors: Huifang Wu; Nick Zink; Lawrence P Carter; Ashok K Mehta; R Jason Hernandez; Maharaj K Ticku; Richard Lamb; Charles P France; Andrew Coop Journal: J Pharmacol Exp Ther Date: 2003-01-21 Impact factor: 4.030
Authors: L Gallimberti; M Cibin; P Pagnin; R Sabbion; P P Pani; R Pirastu; S D Ferrara; G L Gessa Journal: Neuropsychopharmacology Date: 1993-08 Impact factor: 7.853
Authors: Amy K Goodwin; Roland R Griffiths; P Rand Brown; Wolfgang Froestl; Cornelis Jakobs; K Michael Gibson; Elise M Weerts Journal: Psychopharmacology (Berl) Date: 2006-09-20 Impact factor: 4.530
Authors: A K Goodwin; P R Brown; E E W Jansen; C Jakobs; K M Gibson; E M Weerts Journal: Psychopharmacology (Berl) Date: 2009-02-06 Impact factor: 4.530