Figure 13.

Possible mechanisms underlying the reinforcing and analgesic effects of alcohol exposure. (A) Acute alcohol exposure induces eOP release but inhibits Glu release from Glu_ergic neurons, resulting in suppression of GABA_ergic neurons. Downregulation of GABA_ergic neurons disinhibits DA_ergic neurons, resulting in an increase in DA release and ensuing reinforcement. Opioid exposure induces analgesia via cAMP/CREB signaling. (B) In addicted subjects consuming alcohol, OP_ergic, Glu_ergic and GABA_ergic neurons respond like the non-addicted subjects, but DA_ergic neurons and the analgesic pathway are less responsive. Cumulatively, addicted subjects drinking alcohol exhibited poor opioid-induced analgesia and euphoria. (C) Alcohol abstinence in addicted subjects result in hyperactivity of Glu_ergic but downregulation of GABA_ergic neurons, causing neuronal excitation and the withdrawal symptoms. Alcohol resumption restores opioid’s analgesic potency but to a lesser degree, but eOP release is restored.