Action of drugs of abuse on brain reward systems: An update with specific attention to opiates

In addressing the role that the substrate of brain stimulation reward might play in drug abuse, Wise [47] reviewed evidence relating brain stimulation and psychomotor stimulant reward to dopaminergic but not noradrenergic elements identified with brain reward circuitry. He then speculated that one possible mechanism of opiate, ethanol, barbiturate or benzodiazepine reward might involve a specified disinhibition of the dopaminergic element. He suggested that these drugs might have inhibitory actions on locus coeruleus, which in turn might send an inhibitory projection to the dopaminergic link in reward circuitry. This speculation is challenged with respect to ethanol in the companion article [1] and with respect to opiates in the present article. Recent evidence indicates that the rewarding action of opiates is mediated in the region of the dopaminergic cells of the ventral tegmentum and not in the region of the noradrenergic cells of locus coeruleus. Rewarding opiate injections appear to activate the same or a similar dopaminergic link in brain reward circuitry as that thought to be activated through its afferent inputs in the case of brain stimulation reward and activated at its synaptic terminals in the case of psychomotor stimulant reward. Whether other drugs of abuse activate links in brain reward circuitry which function in parallel or in series with the dopaminergic link identified with opiates and stimulants remains an open question.