Recent evidence indicates that many other neurotransmitter and cytokines may be involved in ethanol-mediated alteration in GABAA receptor function and expression. For example, the mGluR5 antagonist 2-methyl-6-(2-phenyl-ethynyl)pyridine (MPEP) modulates the GABAergic effects of ethanol (Besheer and Hodge 2005). Furthermore, the mGluR5 receptor selective agonist (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG) enhances GABA-gated currents via post-synaptic effects in amacrine cells (Hoffpauir and Gleason 2002). Likewise, cytokines may be involved in ethanol-mediated alterations in GABAA receptor function and expression. Tumor necrosis factor α (TNF-α) concentrations in the brain are elevated by ethanol administration (Crews et al. 2006; Kiefer et al. 2002) and this may contribute to a decrease in GABAA receptor α1 subunit expression (Stellwagen et al. 2005) following chronic ethanol exposure. Understanding of the mechanisms of ethanol dependence has been complicated by the multiple actions of ethanol at various neurotransmitters and/or intracellular signaling pathways. Hence, understanding of these interactions between neurotransmitter systems is essential to the development of novel therapeutic targets for alcoholism.
