We view the age-varying genotypic effect of the CHRM2 SNPs as an instance of a gene-environment interaction. In our case the immediate genotypic effects are upon the activation level of the type 2 muscarinic receptors and the environment is the neuroanatomic and neurophysiological context in which the action of the muscarinic receptors is taking place. This environment undergoes significant changes as the brain develops from the early teens into the early twenties, as we have noted above. In the transition from alcohol non-use to regular use of alcohol to alcohol dependence, we note that alcohol consumption has significant effects on the development of addiction in adolescent animals (Guerri and Pascual, 2010; Philpot and Kirstein, 2004; Maldonado-Devincci et al., 2010; Pascual et al., 2009; Coleman et al., 2011) and humans (Alfonso-Loeches and Guerri, 2011; Koob and Volkow, 2010; Guerri and Pascual, 2010; Bava and Tapert, 2010; Bava et al., 2009; Squeglia et al., 2009). The cholinergic M2 receptor gene belongs to a family of muscarinic acetylcholine G-protein coupled receptors with five known subtypes (M1–M5). The M2 receptors in the mesolimbic dopaminergic
