Chronic unpredictable stress enhances cocaine-conditioned place preference in type 1 cannabinoid receptor knockout mice.

Cannabinoid signaling via the type 1 cannabinoid (CB1) receptor modulates the effects of drugs of abuse and the response to exposure to stressors. In addition, exposure to stressors can alter the effects of drugs of abuse. This study examined the effects of exposure to chronic unpredictable stress (CUS) in CB1 receptor knockout (CB1 KO) mice and their wild-type (WT) littermates, using cocaine-conditioned place preference (CPP) to compare their response to cocaine. Mice were untreated or exposed to 2 weeks of CUS. After this period, the acquisition of a cocaine CPP was examined with one of three doses (3.2, 10.0, or 17.0 mg/kg) of cocaine. Untreated CB1 KO and WT mice both acquired the cocaine CPP; however, exposure to CUS enhanced the acquisition of the cocaine CPP in CB1 KO mice, but did not significantly alter the effects of cocaine in WT mice. Taken together, these findings support earlier evidence suggesting a role for the CB1 receptor in the response to stress as well as in the effects of cocaine.