POMC-derived peptides also actively regulate alcohol- and drug-related behaviors. A significant inverse correlation was observed between baseline cortisol levels and craving for alcohol in alcohol-dependent subjects, and treatment with naltrexone (an antagonist at μ-, δ- and κ-opioid receptors) increased plasma cortisol and ACTH levels and decreased alcohol craving and consumption (15). Moreover, enhanced ACTH and cortisol may contribute to alcohol withdrawal symptoms such as stress and depression. Plasma levels of these hormones were elevated immediately after alcohol withdrawal, but normalized over the following two weeks as the severity of withdrawal symptoms decreased (16). In addition, lower cortisol levels were associated with an increased risk of alcoholic relapse (17). Plasma levels of β-endorphin were also reduced during alcohol withdrawal but remained low even when withdrawal symptoms subsided (18). This implies that the reduced level of β-endorphin in alcoholics is unlikely due to alcohol withdrawal, but may be a trait contributing to alcohol craving and consumption. Therefore, a baseline deficiency of β-endorphin is of potential importance in the initiation and maintenance of drug-taking behaviors (19).
