Discrimination of ethanol-nicotine drug mixtures in mice: Dual interactive mechanisms of overshadowing and potentiation

Rationale: One possible basis for the proclivity of ethanol and nicotine co-abuse is an interaction between the discriminative stimulus (S^D) effects of each drug. Objectives: The current work sought to assess the discriminative control of ethanol and nicotine cues in mice trained with drug mixtures and to determine whether interactive mechanisms of overshadowing and potentiation occur. Methods: Male C57BL/6J mice were trained to discriminate ethanol (1.5 g/kg) alone or ethanol plus nicotine (0.4, 0.8, or 1.2 mg/kg base) in experiment 1 and nicotine (0.8 mg/kg) alone or nicotine plus ethanol (0.5, 1.0, or 2.0 g/kg) in experiment 2. Stimulus generalizations of the training mixtures to ethanol, nicotine, and the drug combination were assessed. Results: Ethanol (1.5 g/kg) retained discriminative control despite the inclusion of a progressively larger nicotine dose within the training mixtures in experiment 1. Although the nicotine S^D was overshadowed by ethanol training doses > 0.5 g/kg in experiment 2, nicotine did potentiate the effects of low-dose ethanol. Conclusions: These findings are suggestive of dual mechanisms whereby ethanol (>0.5 g/kg) overshadows the S^D effects of nicotine, and at lower doses (<1 g/kg) the salience of ethanol's S^D effects is potentiated by nicotine. These mechanisms may contribute to the escalation of concurrent drinking and smoking in a binge-like fashion.