Ro15-4513 enhances and attenuates motor stimulant effects of ethanol in rats

Abstract

The actions of the imidazobenzodiazepine, Ro15-4513 (2.5 mg/kg IP), ethanol (0.50 g/kg, 0.75 g/kg, 1.25 g/kg), and Ro15-4513 in combination with ethanol were assessed using low activity male Charles River (CD) rats. Horizontal (ambulatory) and nonhorizontal (rearing, grooming, etc.) activity were measured in the open field with a Digiscan activity system. When Ro15-4513 was given alone, animals responded in a manner similar to that of the control animals. Ethanol alone, however, resulted in a significant enhancement of activity, with the effect being most pronounced at 0.50 g/kg for horizontal activity and 1.25 g/kg for nonhorizontal activity. A potentiation of the ethanol-induced stimulant effect was observed following pretreatment with Ro15-4513 on the horizontal activity measure for the 1.25 g/kg ethanol group. An attenuation of activity was observed for this group on the nonhorizontal activity measure. Ro15-4513, however, did not affect the stimulation produced by the other doses of ethanol on the nonhorizontal measure. The results suggest that possibility of distinct neurochemical mechanisms in the mediation of horizontal and nonhorizontal activity and that, perhaps, GABA-benzodiazepine mechanisms may play different roles in mediating their ETOH-induced stimulant effect.