Diagram of the brain-reward circuitry of the mammalian (laboratory rat) brain, with sites at which various addictive drugs act to enhance brain reward mechanisms and thus to produce drug-seeking behavior, drug-taking behavior, drug-craving, and relapse to drug-seeking behavior. ABN, anterior bed nuclei of the medial forebrain bundle; Acc, nucleus accumbens; AMYG, amygdala; DA, subcomponent of the ascending mesocorticolimbic dopaminergic system that appears to be preferentially activated by addictive drugs; DYN, dynorphinergic neuronal fiber bundle outflow from the nucleus accumbens; ENK, enkephalinergic neuronal fiber bundle outflow from the nucleus accumbens; FCX, frontal cortex; GABA, GABAergic inhibitory fiber systems synapsing in the ventral tegmental area, the nucleus accumbens, and into the vicinity of the locus coeruleus, as well as the GABAergic neuronal fiber bundle outflow from the nucleus accumbens; GLU, glutamatergic neural systems originating in frontal cortex and synapsing in both the ventral tegmental area and the nucleus accumbens; 5HT, serotonergic (5-hydroxytryptamine) fibers, which originate in the anterior raphé nuclei and project to both the cell body region (ventral tegmental area) and terminal projection field (nucleus accumbens) of the DA reward neurons; ICSS, the descending, myelinated, moderately fast conducting component of the brain-reward circuitry that is preferentially activated by electrical intracranial self-stimulation (electrical brain-stimulation reward); LC, locus coeruleus; NE, noradrenergic fibers, which originate in the locus coeruleus and synapse into the general vicinity of the ventral mesencephalic neuronal cell fields of the ventral tegmental area; Opioid, endogenous opioid peptide neural systems synapsing into both the ventral tegmental DA cell fields and the nucleus accumbens DA terminal projection loci; Raphé, brainstem serotonergic raphé nuclei; VP, ventral pallidum; VTA, ventral tegmental area. After [1].