The novel dopamine D3 receptor antagonist, SR 21502, reduces cocaine conditioned place preference in rats

Abstract

Research has shown that dopamine (DA) D3 receptors play a crucial role in cocaine addiction. Recently, there has been a strong focus on the development of DA D3 receptor antagonists as potential pharmacological treatments for cocaine addiction. We investigated the ability of a novel selective D3 receptor antagonist SR 21502 to block the expression of cocaine-induced conditioned place preference (CPP) in rats. CPP was determined using a two-chamber apparatus. All of the animals had free access to both chambers on day 1, followed by 4 alternating conditioning days of cocaine injection (paired chamber) and 4 alternating non-conditioning days with saline (non-paired chamber). On the test day, animals were systemically treated with 0, 3.75, 7.5 or 15mg/kg of SR 21502, 10min prior to being placed in the CPP apparatus, and the time spent in each chamber was recorded for 15min. The amount of time spent in the cocaine-paired chamber on the test and pre-exposure days was analyzed. Vehicle-treated animals spent significantly more time in the cocaine-paired side during the test than during the pre-exposure session, indicating a cocaine CPP. SR 21502 produced a dose-related significant reduction in the time spent in the cocaine-paired side compared to vehicle. The DA D3 receptor antagonist SR 21502 blocks the rat's preference for the cocaine-paired chamber, thereby attenuating the rewarding effect of the cocaine cues. This suggests that this compound may be an effective pharmacological treatment against cocaine addiction.