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BEHAVIORAL PHARMACOLOGY

Discriminative Stimulus Effects of -Hydroxybutyrate (GHB) in Rats Discriminating GHB from Baclofen and Diazepam

Departments of Psychiatry (W.K., R.J.L., C.P.F.) and Pharmacology (W.K., L.P.C., R.J.L., C.P.F.), University of Texas Health Science Center at San Antonio, San Antonio, Texas; and Department of Pharmaceutical Sciences (W.C., H.W., A.C.), University of Maryland, Baltimore, Maryland

-Hydroxybutyrate (GHB) is a drug of abuse with actions at GHB and GABA receptors. This study tried to increase the selectivity of the discriminative stimulus effects of GHB by training animals to discriminate GHB from compounds that share pharmacological mechanisms with GHB. In comparison with a previous GHB versus saline discrimination (group 1), rats were trained to discriminate GHB (200 mg/kg) either from saline and the GABA_B agonist baclofen (3.2 mg/kg) (group 2) or from saline, baclofen, and the positive GABA_A modulator diazepam (1 mg/kg) (group 3). In all groups, GHB produced more than 80% GHB-appropriate responding. Baclofen produced 84% GHB-appropriate responding in group 1 but less than 30% in groups 2 and 3. Diazepam produced 68% GHB-appropriate responding in group 1, 30% in group 2, and only 5% in group 3. The GABA_B receptor antagonists CGP35348[3-[aminopropyl(diethoxymethyl)phosphinic acid] and CGP52432[3-[[[((3,4-dichlorophenyl)methyl]amino]propyl]diethoxymethyl)phosphinic acid] attenuated the discriminative stimulus effects of GHB; CGP35348did so with similar potency in all groups, but CGP52432was significantly less potent in groups 2 and 3 than in group 1. In all groups, the GHB antagonist NCS-382 [(2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene ethanoic acid] partially attenuated the discriminative stimulus effects of GHB. The selective GHB receptor ligand UMB86 (4-hydroxy-4-napthylbutanoic acid sodium) tended to attenuate the discriminative stimulus effects of GHB more in group 3 than in the other groups. The finding that animals can discriminate GHB from baclofen is further evidence that the effects of GHB and baclofen are not identical. Effects that GHB does not share with baclofen may involve GHB receptors or differential interactions with GABA_B receptors.

Address correspondence to: Dr. Wouter Koek, Departments of Psychiatry and Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., Mail Code 7792, San Antonio, TX 78229-3900. E-mail: koek{at}uthscsa.edu

This article has been cited by other articles:

				W. Koek, W. Chen, S. L. Mercer, A. Coop, and C. P. France Discriminative Stimulus Effects of {gamma}-Hydroxybutyrate: Role of Training Dose J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 409 - 417. [Abstract] [Full Text] [PDF]