Dopamine in Drug Abuse and Addiction

Abstract

Imaging studies have provided new insights on the role of dopamine (DA) in drug abuse and addiction in the human brain. These studies have shown that the reinforcing effects of drugs of abuse in human beings are contingent not just on DA increases per se in the striatum (including the nucleus accumbens) but on the rate of DA increases. The faster the increases, the more intense the reinforcing effects. They have also shown that elevated levels of DA in the dorsal striatum are involved in the motivation to procure the drug when the addicted subject is exposed to stimuli associated with the drug (conditioned stimuli). In contrast, long-term drug use seems to be associated with decreased DA function, as evidenced by reductions in D2 DA receptors and DA release in the striatum in addicted subjects. Moreover, the reductions in D2 DA receptors in the striatum are associated with reduced activity of the orbitofrontal cortex (region involved with salience attribution and motivation and with compulsive behaviors) and of the cingulate gyrus (region involved with inhibitory control and impulsivity), which implicates deregulation of frontal regions by DA in the loss of control and compulsive drug intake that characterizes addiction. Because DA cells fire in response to salient stimuli and facilitate conditioned learning, their activation by drugs will be experienced as highly salient, driving the motivation to take the drug and further strengthening conditioned learning and producing automatic behaviors (compulsions and habits).