Oxytocin enhances the expression of morphine-induced conditioned place preference in rats

Drug addiction is characterized by drug-seeking and drug-taking and has devastating consequences on addicts as well as on society. Environmental contexts previously associated with drug use can elicit continued drug use and facilitate relapse. Accumulating evidence suggests that the neuropeptide oxytocin might be a potential treatment for behavioral disorders, including drug addiction. Here, we investigated the effects of central oxytocin administration on the acquisition and expression of morphine-induced conditioned place preference (CPP), a model for measuring the rewarding effects of drugs of abuse, in male Wistar rats. Intracerebroventricular (ICV) administration of oxytocin (0.2 μg) or the specific oxytocin receptor antagonist (OTA), desGly-NH2, d(CH2)5[Tyr(Me)2, Thr4] OVT, (0.75 μg), on the conditioning days did not affect the acquisition of morphine-induced CPP. By contrast, ICV oxytocin, but not OTA, administration immediately prior to the post-conditioning session enhanced the expression of morphine-induced CPP, possibly by activation of oxytocin receptors in the nucleus accumbens shell (NAcSh). The oxytocin enhancement of morphine-induced CPP was not associated with any changes in the locomotor activity of morphine-conditioned rats. Together, these data suggest that central administration of exogenous oxytocin enhances the expression of morphine-induced CPP, at least in part, via activation of oxytocin receptors within the NAcSh.