**3. β-endorphin and alcohol**

POMC is the precursor to all endorphins, including -endorphin, which is synthesized in both the hypothalamus and the anterior pituitary. Endorphin producing neurons are located primarily in the arcuate nucleus of the hypothalamus, and project to other areas of the hypothalamus (supraoptic nucleus, paraventricular nucleus, and lateral hypothalamus) as well as to the amygdala, ventral tegmental area (VTA), periaqueductal gray, and bed nucleus of the stria terminalis (King & Hentges, 2011; McGinty & Bloom, 1983). Thus, βendorphin is well situated to influence reward, stress and pain (see Kreek & Koob, 1998 for review). Moreover, EtOH-initiated dopamine release in the nucleus accumbens (NAC; de Waele & Gianoulakis, 1993; Koob & Le Moal, 1997) is thought to involve endorphin, which hyperpolarizes GABAergic neurons, and thereby disinhibits dopaminergic firing in the VTA (Johnson & North, 1992). Thus, the effects of acute alcohol administration on β-endorphin in the hypothalamus (Gianoulakis, 1990; Sakar et al. 2007) contribute to the positive reinforcing effects of alcohol. Additionally, acute administration of alcohol initiates synthesis and release of β-endorphin into the bloodstream (de Waele & Gianoulakis, 1993; Keith et al., 1986).

The relationship between β-endorphin and alcohol suggests at least two fundamental ways by which this peptide may be contributing to alcoholism. The first may underlie the heritable liability to develop an alcohol use disorder while the second comes into play as βendorphin synthesis is down-regulated following chronic exposure.
