Preclinical evidence indicates that oxytocin influences a number of behavioral and physiological effects of alcohol, including tolerance, withdrawal, and motivational effects (Lee and Weerts, 2016). For example, systemic administration of oxytocin reduces alcohol preference and intake in a variety of drinking models in rats (Bowen et al., 2011; MacFadyen et al., 2016; McGregor and Bowen, 2012) and mice (King et al., 2017; Peters et al., 2013). Direct injection of oxytocin into brain ventricles reduced alcohol consumption and alcohol-induced dopamine efflux in the nucleus accumbens in rats (Peters et al., 2016). Few studies have examined the role of oxytocin receptors in mediating the neuropeptide's effects on motivational actions of alcohol. Recent studies involving viral-mediated overexpression of oxytocin receptors in the nucleus accumbens core have implicated a role for these receptors in alcohol drinking and conditioned reward (Bahi, 2015; Bahi et al., 2016). However, it is noteworthy that oxytocin was shown to block alcohol-induced ataxic and sedative/hypnotic effects via an apparent direct interaction with delta-subunit containing GABA-A receptors (Bowen et al., 2015). Thus, there remains some abiguity as to the role of oxytocin receptors in mediating the neuropeptide's effects on physiological effects of alcohol and, in particular, alcohol-related reward and self-administration behavior.
