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Sunday, July 20, 2008

Gamma-hydroxybutyric acid in male and female cynomolgus monkeys trained to discriminate 1.0 or 2.0 g/kg ethanol.
Behavioural Pharmacology. 19(4):317-324, July 2008.


Gamma-hydroxybutyric acid has been proposed as a pharmacotherapy for alcoholism in part based on similar discriminative stimulus effects as ethanol. To date, drug discrimination studies with [gamma]-hydroxybutyric acid and ethanol have exclusively used rodents or pigeons as subjects.

To evaluate possible differences between species, sex, and route of administration, this study investigated the substitution of [gamma]-hydroxybutyric acid (intragastrically or intramuscularly) for ethanol 30 or 60 min after administration in male (n=6) and female (n=7) cynomolgus monkeys trained to discriminate 1.0 and 2.0 g/kg ethanol. At least one dose of [gamma]-hydroxybutyric acid completely or partially substituted for ethanol in three of the 13 monkeys tested, with each case occurring in female monkeys.

Ethanol-appropriate responding did not increase with [gamma]-hydroxybutyric acid dose. Monkeys were more sensitive to the response rate decreasing effects of [gamma]-hydroxybutyric acid administered intramuscularly compared with intragastrically.

The lack of [gamma]-hydroxybutyric acid substitution for ethanol suggests that these drugs have different receptor bases for discrimination.

Furthermore, the data do not strongly support shared discriminative stimulus effects as the rationale for [gamma]-hydroxybutyric acid pharmacotherapy for alcoholism.


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