Chapter 4 - Endogenous Opiates, Addiction, and the Stress Response

Abstract

Endogenous opioids are peptides produced in a variety of organs but principally by the pituitary and brain. The endogenous opioid system regulates mesolimbic dopamine (DA) and the cortisol response to stress, both of which are implicated in drug and alcohol reward. A considerable body of research has highlighted the relationship between this system and alcohol addiction, and experiments have clearly demonstrated that alcohol affects endogenous opioid activity and receptors. Moreover, differences in the endogenous opioid system appear to be related to differences in alcohol and possibly cocaine consumption. Underscoring the role of this system in addiction, opioid antagonists have efficacy in reducing alcohol and, to some extent, cocaine consumption. Given that alcohol and drug use disorders have high heritability, it is possible that genetic differences in endogenous opioid tone are associated with differing vulnerabilities to alcohol and drug abuse. β-endorphin activity and hypothalamic–pituitary–adrenal (HPA) axis response to opioid receptor antagonists and stress have been shown to differ as a function of family history of alcoholism. Individuals at increased familial risk for alcohol abuse might have altered opioid tone that may modulate mesolimbic DA in ways that enhance reinforcement and reward, and thus addictive behaviors.