The intrinsic and interactive effects of RO 15-4513 and ethanol on locomotor activity, body temperature, and blood...

The ability of the putative ethanol antagonist RO 15-4513 to antagonize ethanol - induced hypoactivity, hypothermia and hyperglycemia was investigated in rats. Although RO 15-4513 produced hypoactivity by itself, it attenuated ethanol - induced hypoactivity. This antagonism suggests that ethanol - induced hypoactivity is mediated by the GABA-benzodiazepine receptor complex which is thought to be the site of action of RO 15-4513. In contrast, although RO 15-4513 produced hypothermia by itself, it had no significant effect on ethanol - induced hypothermia. This suggests that the hypothermic effect of ethanol is not mediated by the GABA-benzodiazepine receptor complex. The fact that RO 15-4513, ethanol and the vehicle all produced hyperglycemia suggests a common stress effect and does not permit any firm conclusions to be drawn as to the interaction between ethanol and RO 15-4513 in modulating glycemic responses. These data indicate that the ethanol antagonism of RO 15-4513 is primarily confined to ethanol's behavioural effects and that ethanol's behavioural and physiological effects are mediated by neurochemically distinct mechanisms.