Pimozide blocks establishment but not expression of cocaine-produced environment-specific conditioning

Two experiments were conducted to examine the effects of pimozide on cocaine-produced conditioning to a specific environmental context. On 8 treatment days, 12 rats were injected with cocaine (10 mg/kg i.p.) and 12 with saline prior to placement for 60 min into a test chamber outfitted with infrared emitters and detectors. Following each treatment session the saline group received cocaine in their home-cages and the cocaine group received saline. Cocaine produced a significant increase in vertical activity on treatment days. On test days all rats received saline. Significantly greater vertical activity was observed in the group previously receiving cocaine in the test environment. All rats then received 8 more treatment sessions. On saline test days, pimozide (0.4 mg/kg i.p.) pretreatment failed to antagonize expression of the conditioned effect. In experiment 2, pimozide was given prior to treatment and no evidence of conditioning was seen on saline test days. Thus, pimozide blocked the establishment but not the expression of cocaine-produced environment-specific conditioning. These results suggest that during conditioning, the effects of cocaine on dopaminergic neurons may have produced a change that subsequently influenced behaviour even when dopaminergic systems were blocked.