COMMENTS: Study is the first to reveal how oxytocin can inhibit addiction mechanisms. It’s well established that oxytocin decreases cravings and drug use in animals addicted to substances. It is also well established that oxytocin is rewarding and activates dopamine in the reward circuitry. This study has oxytocin inhibiting dopamine and addictive behaviors in a very small reward circuitry structure
Department of Psychology, Macquarie University, Sydney, Australia.
The subthalamic nucleus (STh) is increasingly recognised as an important region involved in the motivation for drug reward. It is not yet known if dopamine, the neurotransmitter primarily responsible for reward signaling, is also involved in mediating reward-related activity in the STh. The neuropeptide oxytocin acts within the STh to reduce the rewarding effects of the psychostimulant methamphetamine, through a proposed interaction with dopamine. However, the mechanisms of this interaction are unclear. The current study aimed to determine whether-
(i) dopamine microinjected into the STh would result in a significant place preference following a single-trial conditioning session,
(ii) co-administered dopamine receptor antagonist would block the formation of a conditioned place preference (CPP) for dopamine,
iii) co-administered oxytocin would prevent CPP for dopamine and
(iv) whether the selective oxytocin antagonist desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT, when co-administered with oxytocin and dopamine, would reverse the effects of oxytocin and result in a CPP for dopamine.
Results showed that male Sprague Dawley rats i) formed a preference for the context paired with dopamine (100 nmol/side) administration into the STh, which was prevented by co-administration of ii) the mixed dopamine antagonist fluphenazine (10 nmol/side) or iii) oxytocin (0.6 nmol/side), with the oxytocin effect on dopamine CPP reversed by the co-administration of the oxytocin antagonist (3 nmol/side). These data suggest that dopamine neurotransmission in the STh produces rewarding effects that can be reduced by activation of local oxytocin receptors.