Ethanol-chlordiazepoxide interactions in the rat.

One group of rats (n = 9) was trained to discriminate between the effects induced by 600 mg/kg ethanol and saline, whereas another group (n = 5) had to discriminate between 5.0 mg/kg chlordiazepoxide (CDZ) and saline, administered intraperitoneally (IP) 15 min prior to the training sessions. Once trained, decreasing doses of ethanol in ethanol-trained rats produced decreased discriminative performance; the ED50 was 239.4 mg/kg. Likewise, decreasing doses of CDZ in CDZ-trained rats produced decreased discrimination, with an ED50 = 1.5 mg/kg. Substitution of 1.25-10.0 mg/kg CDZ in ethanol-trained rats produced a transfer of the ethanol-induced interoceptive cue in a dose-responsive manner, whereas ethanol did not substitute for CDZ in CDZ-trained rats. Analysis of dose-response curves suggested that CDZ is acting by a similar mechanism/site in both groups of rats but by a site different than ethanol. Co-administration of the ED50's for ethanol and CDZ in ethanol-trained rats did not produce additive effects. The observed one-way asymmetrical generalization of drug effects, as well as the lack of additive effects of co-administration, are discussed.