Cocaine-Induced Behavioral Sensitization in Mice: Effects of Microinjection of Dopamine D2 Receptor Antagonist into the Nucleus Accumbens

To determine the role of dopamine D2 receptor (D2R) in the nucleus accumbens (NAc) core in cocaine-induced behavioral sensitization, D2R antagonist, raclopride was bilaterally microinjected (2.5 or 5 nmol) into the NAc core of WT and D2R(-/-) mice and the initiation and expression phase of cocaine-mediated locomotor sensitization were analyzed. WT and D2R knockout (D2R(-/-)) mice received bilateral injections of either saline, or raclopride at the NAc core 30 min before each of five daily repeated injections of saline or cocaine (15 mg/kg i.p.). Following 2 weeks of withdrawal after repeated exposure to cocaine, the animals were pre-treated with an intra-accumbal injection of vehicle or raclopride before receiving a systemic cocaine challenge for the expression of sensitization. Animals which had been microinjected raclopride into NAc core displayed the enhancement of cocaine-induced behavioral response for the initiation but also for the expression of sensitization in WT as well as in D2R(-/-) mice, which was thus unaltered as compared to vehicle-injected control group. These results suggest that D2R in NAc core is not involved in cocaine-induced behavioral sensitization.