Oxytocin treatment for alcoholism: Potential neurocircuitry targets

Oxytocin (OT) has gained considerable interest in recent years as a potential treatment for alcoholism and other substance use disorders. Evidence continues to mount that OT administered either centrally, peripherally or intranasally can decrease ethanol intake in both humans and animal models. The potential mechanisms for the ability of OT to decrease ethanol reward, and importantly, cue- and stress-induced ethanol relapse, are explored by reviewing the specific neuronal circuits involved in mediating these actions and their sensitivity to OT. In addition to dopamine neurons that project from ventral tegmental area (VTA) to nucleus accumbens (NAc) to signal positively reinforcing events, OT receptors (OxTR) are also expressed by dopamine neurons that project from VTA to brain regions that can convey aversive properties of a stimulus. Moreover, OxTR are expressed by non-dopaminergic neurons in the VTA, such as GABA and glutamate neurons, which can both modulate the activity of dopamine VTA neurons locally (in opposite directions) or can project to other brain regions, including the NAc, where it can alter either positive reinforcement or aversion caused by ethanol. The ability of OT to regulate limbic circuitry and the hypothalamic-pituitary-adrenal axis is discussed as a potential mechanism for the ability of OT to inhibit ethanol-induced negative reinforcement. Together, understanding the diversity and complexity of OT regulation of ethanol reward may contribute to more effective use of OT as pharmacotherapy for alcohol use disorder. This article is part of the special issue on Neuropeptides.