Alcohol use is a major cause of disability worldwide 1, but available treatments have limited efficacy 2. Development of novel, mechanism-based pharmacotherapies will require an improved understanding of the neurobiology that underlies addictive properties of alcohol 3. Compared to other addictive drugs, alcohol has a complex pharmacology. Sedative, ataxic and anxiolytic alcohol effects are primarily mediated through GABA- and glutamate signaling. In contrast, rewarding properties of alcohol such as euphoria and psychomotor stimulation are thought to involve endogenous opioids and mesolimbic dopamine (DA). In response to alcohol, µ-opioid receptor (OPRM1) activation in the ventral tegmental area (VTA) suppresses the activity of inhibitory GABA-ergic interneurons, resulting in disinhibition of DA-neurons and DA release from their terminals in the ventral striatum 4. Accordingly, OPRM1 blockade is a treatment for alcohol dependence 3.
