Figure 1.

Neural circuitry implicated in reward and underlying addiction. Several brain regions are directly involved in modulating reward and are associated with the pathology of substance abuse disorders. Dopaminergic VTA projection neurons (dotted purple lines) innervate the NAc and mPFC, as well as the hippocampus and amygdala. GABAergic afferents from the NAc (some direct and some indirect) (solid blue line) provide inhibitory feedback to dopaminergic VTA neurons. Excitory glutamatergic afferents (solid red lines) project to the NAc from the mPFC, hippocampus, and amygdala, as well as glutamatergic innervation of the VTA by the amygdala and hippocampus. Each region contains specialized cell types believed to play crucial roles in both natural reward phenomena and addiction-related phenotypes. These cell types, color-coded in the key, include amygdala (green) and NAc (purple) medium spiny neurons, mPFC (pink) and hippocampal CA3 (blue) pyramidal neurons, and VTA dopamine neurons (orange). Not shown are serotonergic projections from the DR and noradrenergic projections from the LC. Psychostimulants, as well as other drugs of abuse, robustly modulate the structural plasticity of individual neurons within these regions. Nissl-stained coronal sections of the (A) mPFC, and (B) NAc, with the left hemisphere of each marked schematically to represent subregions of interest. mPFC, Medial prefrontal cortex; NAc, nucleus accumbens; C-P, caudate-putamen; VP, ventral pallidum; LH, lateral hypothalamus; VTA, ventral tegmental area; SNr, substantia nigra; DR, dorsal raphe; LC, locus coeruleus; ACA, anterior cingulated; PL, prelimbic cortex; IL, infralimbic cortex; NAcc, nucleus accumbens core; NAcs, nucleus accumbens shell. (Adapted, with permission, from Russo et al. 2009.)