Stimuli associated with cocaine injections acquire the ability to enhance the behavioral actions of cocaine during subsequent administrations. We have found that such conditioned cocaine sensitization can be prevented by administering haloperidol together with cocaine during the conditioning session. We have extended these findings by showing that both D1 antagonists (SCH-23390) as well as D2 antagonists (raclopride and sulpiride) administered together with cocaine on the conditioning day will prevent the development of conditioned sensitization. Neither the D1 nor the D2 antagonist is able to prevent the expression of conditioned sensitization when administered on the test day. Rats trained under cocaine show conditioned cross-sensitization to quinpirole (D2 agonist) and apo- morphine (mixed D1 and D2 agonist). On the other hand, when animals are trained under either a D2 agonist (quinpirole) or a D1 agonist (6-chloro-APB), they do not show cross-sensitization to cocaine. Cross- sensitization is found, however, when rats are injected with both D1 and D2 agonists on day 1. Cross-sensitization was also found between MK-801 and cocaine, suggesting involvement at a glutamatergic mechanism in cocaine-induced sensitization. Lesions of the amygdala and nucleus accumbens disrupt cocaine-induced conditioned sensitization when one day of training is employed, but not when animals are trained for three days.
