Effects of combining ethanol (EtOH) with gamma-hydroxybutyrate (GHB) on the discriminative stimulus, locomotor, and motor-impairing functions of GHB in mice

Abstract

Gamma-hydroxybutyrate (GHB) is a drug of abuse that is often coabused with ethanol (EtOH) and has been implicated as a date rape agent in conjunction with EtOH. Much information is lacking regarding the manner in which GHB interacts with EtOH. This study was designed to further characterize the behavioral effects of GHB alone and in combination with EtOH in male Swiss-Webster mice. The effects of GHB (0.1-1.0 g/kg) and EtOH (2.0-5.0 g/kg) alone, as well as the effects of GHB in combination with EtOH, were examined using an automated locomotor activity procedure, a functional observational battery (FOB) and a GHB drug discrimination procedure. GHB decreased, whereas EtOH had little effect on locomotor activity. In the FOB, EtOH dose-dependently decreased activity in combination with 0.3 g/kg GHB. Alone, each drug had little effect on the righting reflex, but combining ineffective doses of GHB and EtOH significantly impaired righting. GHB and EtOH decreased forelimb grip strength. Combinations of ineffective doses of GHB and EtOH decreased forelimb grip strength when given together. GHB and EtOH impaired inverted screen performance, and EtOH increased the impairing effects of low, but not high, doses of GHB. GHB and EtOH increased hind limb splay, and EtOH increased the effects of 0.1 and 0.3 g/kg GHB on splay. GHB and EtOH decreased body temperature, and EtOH augmented the temperature-decreasing effects of GHB. EtOH produced less than 50% GHB-like discriminative stimulus effects, and GHB failed to alter the GHB-like discriminative stimulus effects of EtOH. Overall, EtOH increased the effects of GHB on several gross measures of behavior and only partially occasioned the discriminative stimulus properties of GHB.