Although different drug classes act on distinct cellular substrates, initial drug reward/saliency appears to be primarily encoded by midbrain dopamine neurons projecting into the prefrontal cortex as well as the dorsal and ventral striatum (Volkow, Fowler, Wang, Baler, & Telang, 2009). Human imaging studies indicate the extent to which a drug increases striatal dopamine is proportional to self-reported euphoria (Drevets et al., 2001; Sharma & Brody, 2009; Volkow, et al., 2009). Nonetheless, it is important to note that responding for rewarding stimuli is also encoded by other ascending monoamine fibers such as norepinephrine (Stein & Himwich, 1962) and other non-dopaminergic systems within the medial forebrain bundle (Crow, 1973).
