Cross-sensitization between the locomotor stimulant effects of ethanol and those of morphine and cocaine in mice

Background: Drugs of abuse may share some common mechanisms of action. We examined this idea by determining whether cross-sensitization would occur between the locomotor stimulant effects of ethanol (EtOH) and those of morphine and cocaine. Methods: Genetically heterogeneous adult female mice were repeatedly treated with 2.5 g/kg EtOH, then challenged 24 hr later with one of four doses of morphine or cocaine (0, 5, 10, or 20 mg/kg for both drugs). Under the reciprocal conditions, mice were repeatedly injected with cocaine or morphine (10 or 20 mg/kg), then challenged 24 hr later with 2.0 g/kg EtOH. In all cases, locomotor responses were compared to those of repeatedly saline-treated control groups. Results: Behavioral sensitization was seen to the stimulant effects of EtOH, and to the effects of the higher, 20 mg/kg dose of both morphine and cocaine. EtOH-sensitized mice did not show cross-sensitization to morphine or cocaine. However, both single and multiple morphine pre-exposures induced enhanced activation to an EtOH challenge. Mice repeatedly injected with 10 or 20 mg/kg cocaine also exhibited increased sensitivity to the stimulant effects of EtOH. Conclusions: There is some overlap in the neural mechanisms underlying behavioral sensitization to the locomotor stimulant effects of EtOH and those mediating sensitization to the locomotor stimulant effects of morphine and cocaine. Differences seen under reciprocal treatments may be associated with conditioning factors, or reflect differences in the neurobiological specificity of the effects of these drugs.