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.
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.
Colombo
G
G
C. N. R. Center for Neuropharmacology, University of Cagliari, Via Porcell 4, I-09124, Cagliari, Italy. colomb@unica.it
Agabio
R
R
Carai
M A
MA
Lobina
C
C
Pani
M
M
Reali
R
R
Gessa
G L
GL
D000818:Animals; D004192:Discrimination, Psychological; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D006885:Hydroxybutyrates / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D006885:Hydroxybutyrates; C111420:4-hydroxybutyric acid; D000431:Ethanol; D005680:gamma-Aminobutyric Acid