Despite the lack of understanding of alcohol’s impact on human neurons, rodent studies have provided us with invaluable information. Ethanol, also known as ethyl alcohol, produces its clearest presynaptic effects at GABAergic synapses in several brain regions in rodents (Lovinger, 2018) Specifically, early electrophysiological studies established that ethanol consistently and reproducibly potentiated GABA-mediated inhibitory transmission, and this was described as one of the clearest synaptic effects of the drug (Wan, Berton, Madamba, Francesconi, & Siggins, 1996; Weiner, Gu, & Dunwiddie, 1997). This effect was observed at GABAergic synapses in many brain regions, including the hippocampus (Ariwodola & Weiner, 2004; Sanna et al., 2004), basolateral amygdala (Butler, Chapell, & Weiner, 2014; Karkhanis, Alexander, McCool, Weiner, & Jones, 2015; Talani & Lovinger, 2015), central amygdala (Bajo, Cruz, Siggins, Messing, & Roberto, 2008), cerebellum (Kelm, Criswell, & Breese, 2008), dorsal striatum (Wilcox et al., 2014), nucleus (Hyytiä & Koob, 1995), spinal cord (Ziskind-Conhaim, Gao, & Hinckley, 2003), and ventral tegmental area (VTA) (Theile, Morikawa, Gonzales, & Morrisett, 2008). It was hypothesized that one mechanism of the rewarding properties of ethanol could be a result of a disinhibitory mechanism involving opioid receptors that are expressed on VTA interneurons (Xiao, Zhang, Krnjević, & Ye, 2007).
