Discriminative stimulus properties of ethanol: effects of cumulative dosing and Ro 15-4513.

A cumulative dose-testing procedure was developed to assess the stimulus control of ethanol (EtOH). This procedure was then used to examine the interaction between EtOH and the imidazobenzo-diazepine Ro 15-4513 in rats trained to discriminate between EtOH (lg/kg) and saline. Rebreathed air was used to assess concentrations of EtOH. When injected as a single dose (lg/kg), the concentration of EtOH in the breath did not differ significantly from the final concentration of the same amount administered cumulatively (0.25 + 0.25+0.5g/kg = lg/kg). Likewise, the generalization gradient of cumulatively administered EtOH did not differ from the gradient obtained when the three doses of EtOH were tested on separate days. The ED(50) values were 0.41g/kg for the cumulative, and 0.5g/kg for the separate administrations. Drug stimulus control was examined after 0.25, 0.5 and 1g/kg of EtOH. In combination with Ro 15-4513 (0.1-30mg/kg), administered 5min prior to the first dose of EtOH, a slight attenuation of the discriminative response to EtOH by Ro 15-4513 was seen with half (0.5g/kg) the training dose of EtOH. However, the slope function of the regression was fairly flat. Ro 15-4513 did not significantly change stimulus control induced by 0.25 and 1g/kg of EtOH. Response-times were significantly longer as a function of Ro 15-4513 dose, particularly during the first test.