Brain mechanisms of drug reward and euphoria

Abstract

Drugs of abuse have in common the fact that they serve as biological rewards. They presumably do so because of their ability to activate endogenous brain circuitry. By determining the brain circuitry activated by rewarding drug injections, much can be learned about the degree to which there is a common basis for the abuse liability of seemingly different drugs. The brain circuitry activated by two classes of abused drugs, psychomotor stimulants and opiates, is now partially understood; the current evidence suggests a shared mechanism of stimulant reward and opiate reward. The identified portion of the circuitry involves dopamine-containing cells of the ventral tegmental area and their fiber projections to the cells of the nucleus accumbens. Morphine activates these cells in the region of the cell bodies; it may have direct actions on receptors imbedded in the dopaminergic cell membrane, or it may act on afferent terminals that synapse on the dopaminergic cell bodies or dendrites. Cocaine and amphetamine act at the terminals of the dopaminergic fibers to nucleus accumbens and perhaps other structures. The shared activation of the dopaminergic input to nucleus accumbens accounts for the behaviorally activating and the rewarding effects of both stimulants and opiates (the opiate stimulant action is not widely known because it is usually masked by depressant actions of opiates in other, antagonistic, brain circuits). The activation of dopaminergic systems also accounts for amphetamine euphoria; it almost certainly accounts for cocaine euphoria and it probably accounts for opiate euphoria as well. Opiates and psychomotor stimulants clearly have many other actions which are not shared; nonshared actions must account for the well-known differences in the subjective effects of opiates and stimulants. One of the major nonshared actions is physical dependence. Opiates gain access to a major component of the circuitry mediating opiate physical dependence through opiate receptors in the periaqueductal gray matter. This receptor population is anatomically distinct from the population mediating the rewarding effects of opiates in nondependent animals. While both opiates and stimulants can activate (though by quite different mechanisms and at quite different loci) the dopaminergic circuitry underlying reward phenomena, only opiates activate the separate circuitry underlying dependence phenomena.(ABSTRACT TRUNCATED AT 400 WORDS)