The oxytocin receptor impairs ethanol reward in mice.

It is well established that oxytocin, and its receptor (OxtR), play a crucial role in addiction and that the stimulation of oxytocin neurotransmission reduces addictive behaviors to ethanol in laboratory animals. However, the impact of OxtR modulation on acquisition, extinction and reinstatement of drug-elicited ethanol-conditioned place preference (EtOH-CPP) has not yet been investigated. In this study, we evaluated the effects of OxtR pharmacological modulation, using the oxytocin analog Carbetocin, and genetic overexpression in the nucleus accumbens (NAcc), using lentiviral-mediated gene transfer technology, of the OxtR on acquisition, extinction and reinstatement of drug-elicited EtOH-CPP in mice. In the first experiment, results showed that Carbetocin administration and NAcc OxtR-overexpression (LV-OxtR) reduced EtOH-CPP establishment. In the second experiment, systemic Carbetocin treatment and OxtR overexpression resulted in decreased time spent in the ethanol-paired compartment following completion of a 7-day extinction protocol. Finally, the third experiment showed that Carbetocin and LV-OxtR suppressed primed reinstatement of EtOH-CPP. It is concluded that pharmacological and genetic modulation of the OxtR can modulate the acquisition, extinction, and reinstatement of conditioned reinforcing effects of ethanol. Taken together, the current findings add to the growing literature on oxytocin neurotransmission modulation in the pharmacotherapy of ethanol addiction and alcoholism.