The dopamine D3 receptor antagonist, SR 21502, facilitates extinction of cocaine conditioned place preference

Pharmacotherapeutic agents that could facilitate extinction of cocaine cues would be useful in the treatment of cocaine addiction. We tested whether SR 21502, a selective dopamine (DA) D3 receptor antagonist, can facilitate extinction of cocaine conditioned place preference (CPP) in rats.

In experiment 1, cocaine (10mg/kg) CPP was first established and then extinguished. During the extinction phase the rats were injected with SR 21502 and placed in the previously cocaine-paired compartment for four sessions and vehicle in the other compartment on four alternating sessions. The rats were then tested again for cocaine CPP. In experiment 2, different groups of rats were trained to associate SR 21502 with one compartment and saline with the other.

In experiment 1, the animals spent significantly more time in the cocaine-paired compartment after cocaine conditioning than they did before conditioning. Subsequently, the animals treated with SR 21502 during the extinction phase spent significantly less time in the cocaine-paired compartment than the vehicle group. In experiment 2, animals conditioned with SR 21502 preferred neither side of the CPP apparatus, indicating that SR 21502 produced no effects of its own.

These findings suggest that treatment with SR 21502, a DA D3 receptor antagonist, in the presence of cocaine cues can facilitate extinction of cocaine CPP and further suggest that this compound might be an effective cocaine addiction treatment.