Drug and alcohol dependence can be characterized by a dysfunction in learning and memory processes that leads to drug craving and seeking behaviors that involve prefrontal cortical, midbrain (VTA) and hippocampal circuits. G protein-coupled inwardly rectifying potassium (GIRK) channels are known to play a critical role in this process (Crabbe et al., 2006; Tipps and Buck, 2015). GIRK channels are direct targets of alcohol and mediate behaviors associated with alcohol dependence including regulation of VTA dopamine tone during dependence. (Aryal et al., 2009; Blednov et al., 2001; Goldman et al., 2005b; Kozell et al., 2009; Lewohl et al., 1999; Herman et al., 2015). A potassium channel gene variant, KCNJ6 (GIRK2) was associated with alcohol dependence in a study of densely affected families (Kang et al., 2012). The function of this variant mediated alterations in the theta band of event related oscillations, which index the activity of neuronal ensembles while performing a task and are important for processes underlying frontal inhibitory control, conscious awareness, recognition memory and episodic retrieval (Kang et al., 2012). Collectively, potassium/GIRK channels appear to be compelling genetic candidates mediating cognitive and executive function deficits in alcohol dependence.
