Fig. 1: Diagramatic representation of the possible interactions between the endogenous opioid system and the brain nuclei responsible for mediating the positive reinforcing effects of ethanol. A10 dopaminergic (DA) neurons, whose cell bodies are located in the ventral tegmental area (VTA) and whose axonal terminals are in the nucleus accumbens, are under tonic GABAergic inhibition. This inhibition may be removed when μ opioid receptors (located in the cell body of the GABA interneuron) are stimulated either by β -endorphin (originating in the arcuate nucleus and projecting to the VTA) or by enkephalins. In addition, DA release may be increased by stimulation of δ or μ opioid receptors in the nucleus accumbens. Ethanol stimulates β -endorphin or enkephalin release, and this may lead to increased DA release in the nucleus accumbens. In contrast, stimulation of κ opioid receptors in the nucleus accumbens by dynorphin peptides decreases DA release and may produce aversive states. GABA, γ-aminobutyric acid; β -EP, β -endorphin, ENK, enkephalin; DYN, dynorphin; (–) indicates inhibition; (+) indicates stimulation. Reproduced from Jamensky and Gianoulakis,36 with permission of the publisher.