Oxytocin also appears to directly interact with the GABAergic system, which may be of particular significance for alcohol addiction. Oxytocin receptors have been localized on GABAergic interneurons in the NAc (Dolen et al., 2013), central amygdala (Huber et al., 2005), hippocampus (Zaninetti and Raggenbass, 2000) and PFC (Li et al., 2016, Nakajima et al., 2014). There is also some evidence that OXTR-expressing cells contain GABA (Yoshida et al., 2009), implicating a role for OXT in the modulation of inhibitory tone. Indeed, OXT administration has been shown to effect GABAergic transmission in multiple brain regions critical to the addiction process and may regulate both drug-seeking and anxiety-related behaviors through interactions with its own receptor or by binding directly to GABA receptors (Bowen et al., 2015). For instance, OXT administration blocked the faciliatory effects of acute alcohol on GABA in the central amygdala of alcohol dependent, but not nondependent rats (Tunstall et al., 2019). Additionally, there is some evidence to suggest that OXT may also modulate GABAergic transmission via direct interaction with GABAA receptors (Bowen et al., 2015, Dong et al., 2017).
