The specific circuitry that is associated with drug reward has been broadened to include many neural inputs and outputs that interact with the basal forebrain. As the understanding of the relevant circuits has evolved, so too has the understanding of the relevant neurotransmitters and neuromodulators, which include not only dopamine and opioid peptides but also γ-aminobutyric acid (GABA), glutamate, serotonin, acetylcholine, and endocannabinoid systems that act at the level of either the ventral tegmental area or nucleus accumbens (figure 1; tables 1, 2 for neurotransmitter systems and specific neurocircuits involved). Balanced circuits result in proper inhibitory control and decision making and normal functioning of reward, motivation, stress, and memory circuits. These circuits also interact with circuits that are involved in mood regulation, including stress reactivity (which involves the amygdala, hypothalamus, and habenula) and interoception (which involves the insula and anterior cingulate cortex and contributes to the awareness of negative emotional states). Drugs of abuse usurp executive function circuits, motivational circuits, and stress circuits via multiple neurotransmitter-specific neuroplasticity circuits (tables 1, 2). Key neurotransmitters that are implicated in these neuroadaptations include dopamine, enkephalins, glutamate, γ-aminobutyric acid, norepinephrine, corticotropin-releasing factor (CRF), dynorphin, neuropeptide Y, and endocannabinoids (tables 1, 2).
