OPPONENT PROCESS MODEL AND PSYCHOSTIMULANT ADDICTION

There are many sources of reinforcement in the spectrum of cocaine dep endence that contribute to the compulsive cocaine self-administration or loss of control of cocaine intake that constitutes the core of mode rn definitions of dependence. The development of withdrawal has long b een considered an integral part of drug addiction but has lost its imp act in the theorization of drug dependence because of new emphasis on the neurobiological substrates for the positive reinforcing properties of drugs. The present treatise reviews the neurobiological substrates for the acute positive reinforcing effects of cocaine and what is beg inning to be known about the neurobiological substrates of cocaine wit hdrawal. The concept of motivational or affective withdrawal is reintr oduced, which reemphasizes opponent process theory us a model for the motivational effects of cocaine dependence. The same neural substrates hypothesized to be involved in the acute reinforcing properties of dr ugs (basal forebrain regions of nucleus accumbens and amygdala) are hy pothesized to be altered during chronic drug treatment to produce the negative motivational states characterizing drug withdrawal. Within th ese brain regions, both the neurochemical system(s) on which the drug has its primary actions and other neurochemical systems may undergo ad aptations to chronic presence of the drug. An understanding of the ada ptations of the motivational systems of the brain accompanying cocaine dependence leads to important predictions not only about the etiology , treatment, and prevention of cocaine addiction but also about the vu lnerability of these motivational systems in non-drug-induced psychopa thology. (C) 1997 Elsevier Science Inc.