Repeated cocaine administration induces behavioral sensitization and corresponding decreased extracellular dopamine responses in caudate and accumbens.

Behavioral and brain regional dopamine responses to cocaine (10 mg/kg) were concurrently monitored using in vivo microdialysis in freely-moving rats pretreated with 4 daily injections of saline or cocaine (10 mg/kg). Repeated cocaine produced a behavioral sensitization characterized by a downward oriented locomotor activation profile. In contrast, both caudate and nucleus accumbens dopamine responses were significantly diminished in the drug-pretreated group. These results, obtained following two days of drug withdrawal, differ from previous reports of an enhanced dopamine response after longer withdrawal intervals. While the duration of withdrawal may play an important role in the quantitative features of the dopamine response to subsequent stimulant administration, these results suggest that an enhanced dopamine response may not be required for the expression of behavioral sensitization. A compensatory increase in the dopamine uptake carrier, resulting from chronic cocaine-induced uptake blockade, is discussed as a possible mechanism underlying the reduced dopamine response.