Ligand-gated ion channels, including the N-methyl-D-aspartate (NMDA) and GABAA receptors are targets for the actions of alcohol (Vengeliene et al., 2008) and these may play a role in the development of alcohol use disorders. In the central nervous system (CNS), NMDA receptors play important roles in synaptic transmission, synaptic plasticity (such as long-term potentiation), and excitotoxicity (Nagy, 2004). The conventional NMDA receptor is a tetrameric structure consisting of two NR1 and two NR2 (NR2A-D) subunits (Bigge, 1999) that surround a cation channel with a high permeability to calcium (Cavara and Hollmann, 2008). Under normal resting conditions the NMDA receptor is blocked by magnesium (Mg2+) ions, which reside inside the channel pore. This blockade is removed upon membrane depolarization in conjunction with the combined binding of the agonist glutamate and the co-agonist glycine. Because these channels are activated only when electrical and chemical signals are present simultaneously, NMDA receptors are thought to act as coincidence detectors (Nagy, 2008b).
