Characterization of the discriminative stimulus effects of gamma-hydroxybutyric acid as a means for unraveling the neurochemical basis of gamma-hydroxybutyric acid actions and its similarities to those of ethanol

Colombo, Giancarlo; Agabio, Roberta; Carai, Mauro A.M; Lobina, Carla; Pani, Marialaura; Reali, Roberta; Gessa, Gian Luigi

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Volume 20, Issue 3 , Pages 237-245, April 2000

Characterization of the discriminative stimulus effects of gamma-hydroxybutyric acid as a means for unraveling the neurochemical basis of gamma-hydroxybutyric acid actions and its similarities to those of ethanol☆

Giancarlo Colombo
- C. N. R. Center for Neuropharmacology, University of Cagliari, Via Porcell 4, I-09124, Cagliari, Italy
- Corresponding author. Tel.: +39-070-675-8422; fax: +39-070-657-237.(G. Colombo)
Roberta Agabio
- Bernard B. Brodie Department of Neuroscience, University of Cagliari, Via Porcell 4, I-09124, Cagliari, Italy
Mauro A.M Carai
- Bernard B. Brodie Department of Neuroscience, University of Cagliari, Via Porcell 4, I-09124, Cagliari, Italy
- Neuroscienze S.c.a. r.l., Via Palabanda 9, I-09123 Cagliari, Italy
Carla Lobina
- Bernard B. Brodie Department of Neuroscience, University of Cagliari, Via Porcell 4, I-09124, Cagliari, Italy
- Neuroscienze S.c.a. r.l., Via Palabanda 9, I-09123 Cagliari, Italy
Marialaura Pani
- Bernard B. Brodie Department of Neuroscience, University of Cagliari, Via Porcell 4, I-09124, Cagliari, Italy
Roberta Reali
- Neuroscienze S.c.a. r.l., Via Palabanda 9, I-09123 Cagliari, Italy
Gian Luigi Gessa
- C. N. R. Center for Neuropharmacology, University of Cagliari, Via Porcell 4, I-09124, Cagliari, Italy
- Bernard B. Brodie Department of Neuroscience, University of Cagliari, Via Porcell 4, I-09124, Cagliari, Italy
- Neuroscienze S.c.a. r.l., Via Palabanda 9, I-09123 Cagliari, Italy

Received 7 May 1998; received in revised form 9 June 1998; accepted 16 June 1998.

Abstract

The present paper reviews the drug discrimination studies, both from the literature and from this laboratory, conducted to investigate the pharmacological profile of the discriminative stimulus effects of gamma-hydroxybutyric acid. Collectively, the results of these studies suggest that: (1) the discriminative stimulus effects of gamma-hydroxybutyric acid are composed of different cues, each one being the effect of gamma-hydroxybutyric acid on a specific receptor system; (2) the proportion of each component cue varies as the training dose of gamma-hydroxybutyric acid is increased; (3) the gamma-aminobutyric acid B-mediated cue is a major ingredient of the mixed stimulus of gamma-hydroxybutyric acid, but it is more prominent at high training doses than at low training doses of gamma-hydroxybutyric acid; and (4) positive modulation of the gamma-aminobutyric acid A receptor is a relevant part of the discriminative stimulus effects of low gamma-hydroxybutyric acid doses. Finally, data indicating symmetrical generalization between the discriminative stimulus effects of a specific range of doses of gamma-hydroxybutyric acid and those of ethanol are discussed in regard to their further support of the hypothesis that gamma-hydroxybutyric acid may exert its antialcohol effects through a substitution mechanism.

Keywords: Gamma-hydroxybutyric acid, Discriminative stimulus effects, Compound stimulus, GABA_A- and GABA_B-mediated component, Ethanol, Symmetrical generalization, Substitution mechanism