The dopamine D3 receptor antagonist YQA14 that inhibits the expression and drug-primed reactivation of morphine-induced conditioned place preference in rats

Increasing evidence suggests that the mesolimbic dopamine system plays a critical role in opioid addiction. However, there is currently no standard drug treatment for opioid addiction. Growing preclinical evidence indicates that the dopamine D₃ receptor antagonists are the potential anti-addiction pharmacotherapeutic agents based on in animal models of multiple drug addiction. In this study, we investigated the inhibitory effects of YQA14, a novel dopamine D₃ receptor antagonist with a high affinity and selectivity for dopamine D₃ receptor, using morphine-induced conditioned place preference (CPP) in rats. The results suggested that YQA14 (6.25-25mg/kg; intraperitoneal, i.p.) decreased the expression of morphine (10mg/kg, s.c.)-induced CPP in a dose-related manner but did not influence the acquisition of morphine-induced CPP. At a 25mg/kg dose of YQA14, it also notably inhibited the reactivation of morphine-priming CPP. These findings suggest that YQA14 is a potential agent for anti-opioid addiction which warrants further study and development.

Addiction; Conditioned place preference; D(3) receptor; Opioid; YQA14.