The glutamatergic system, the major excitatory system in the central nervous system, is of particular relevance to addiction through the network of interactions with dopaminergic and GABAergic transmission that underlie alcohol and drug craving and relapse. Glutamate receptors work in synergy with dopamine receptors in dendritic spines of medium-sized spiny neurons in the striatum (Cahill, Salery, Vanhoutte, & Caboche, 2014). Epi-static interactions of glutamatergic and dopaminergic genes have been claimed in alcoholics (Puls et al., 2008). Acute and chronic exposure to alcohol affects glutamate transmission (Ding, Engleman, Rodd, & McBride, 2012) and hyperfunctioning of glutamate transmission has been observed during ethanol or drug withdrawal (Hermann et al., 2012; Prior & Galduroz, 2011). Conditional knockout of the NMDA receptor GluN2B subunit in mice eliminates LTP in the bed nucleus of the stria terminalis (Wills et al., 2012) and makes the animals more sensitive to the locomotor effects of ethanol (Badanich et al., 2011). Pharmacological manipulations have demonstrated that activation of group II metabotropic glutamate receptors decreases alcohol (Rodd et al., 2006; Zhao et al., 2006) and cocaine (Jin et al., 2010) seeking and decreases alcohol-induced neurodegeneration (Cippitelli et al., 2010) in rats.
