Brain reward circuitry: Four circuit elements "wired" in apparent series

Activation of a variety of anatomically distinct sites in the central nervous system can produce rewarding states. Four central reward phenomena are amphetamine injections into nucleus accumbens, morphine injections into the ventral tegmental area, electrical stimulation of the ventral tegmental area, and electrical stimulation of the lateral hypothalamic medial forebrain bundle. Current evidence suggests that these four rewarding events trigger activity in elements of a common reward circuit and that the elements are connected in series. The four partially identified elements in this circuit are 1. (1) descending, fast-recovering, short refractory period fibers of the medial forebrain bundle, 2. (2) separate, opioid peptide-containing afferents to the ventral tegmental area, 3. (3) the dopaminergic cells projecting from the ventral tegmental area to nucleus accumbens, and 4. (4) the dopaminoceptive cells of nucleus accumbens.