Genes coding for glutamate receptors and genes coding for proteins that regulate glutamate receptor function are very important in addiction biology and are therefore promising candidates as addiction risk genes. The N-methyl-D-aspartate (NMDA) glutamate receptor, for example, is one of the most potent brain targets for ethanol (Grant and Lovinger, 1995; Manolio et al., 2009). Ethanol’s blockade of glutamate receptors contributes to features of human ethanol intoxication (Girard et al., 2011). Similarly, neuroadaptations in NMDA, AMPA, and several metabotropic glutamate receptors contribute to features of tolerance, sensitization, and withdrawal from ethanol, opiates, nicotine, and cocaine (Kalivas, 2009; Krystal et al., 2003b; Liechti and Markou, 2008; Manolio et al., 2009; Siggins et al., 2003). Some of these neuroadaptations may be downstream consequences of the capacity of drugs of abuse to stimulate the release of dopamine and, as a downstream consequence of dopamine-related signaling mechanisms, to regulate NMDA receptors (Rasmussen et al., 1991).
