Busse and Riley [Biol. Psychiatry 26 (2002) 1373] have recently reported that alcohol dose dependently attenuated cocaine-induced place preferences. Although the mechanism for this effect is not known, it is possible that it is due to alcohol potentiating the aversive properties of cocaine, a potentiation that masks or abates cocaine's rewarding effects in this preparation. Given that the affective properties of cocaine (both aversive and rewarding) have been reported to be dose dependent, it might be expected that alcohol's ability to affect cocaine-induced place preferences would be influenced by changes in cocaine dose. To address this possibility, the following experiments assessed the effects of alcohol (0.5 g/kg) on place preferences induced by high (20, 30 and 40 mg/kg: Experiment 1) and low (2.5 and 5 mg/kg; Experiment 2) doses of cocaine. Specifically, every other day for four cycles male Sprague-Dawley rats were injected with cocaine, alcohol or one of several cocaine/alcohol combinations immediately before being placed on one side of a two-compartment place preference chamber. On alternate days, they were placed on the other side of the chamber after being injected with the drug vehicle(s). In Experiment 1, all doses of cocaine (20, 30 and 40 mg/kg) produced a significant preference for the drug-paired compartment, whereas alcohol alone produced no effect. When given in combination, alcohol attenuated the cocaine-induced place preference (at 30 and 40 mg/kg cocaine). In Experiment 2, neither cocaine (2.5 or 5 mg/kg) nor alcohol produced a significant effect when given alone. However, animals receiving the combination of alcohol and cocaine (5 mg/kg) displayed a significant place preference. These findings indicate that alcohol can both weaken and strengthen cocaine-induced place preferences, possibly via its effects on the rewarding and aversive properties of cocaine. The effect of alcohol is dependent on the dose of cocaine.
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