Molecular Mechanisms of Opiate Addiction in the Nucleus Accumbens: Morphine Regulation of G Proteins

Addiction exacts enormous costs on society in terms of both its clinical and social ramifications. Addiction, defined as the compulsive use of a drug despite adverse consequences, is thought to develop as a result of adaptive changes in specific brain areas. The persistence of these progressively developing adaptations in brain function suggests that long-lasting changes in the brain are important in mediating addictive phenomena. The adaptations associated with compulsive drug use are defined by the terms tolerance, sensitization, dependence, and withdrawal. Tolerance develops when repeated administration of a drug produces a decreased effect or when increasing doses must be administered to obtain the effect observed with the original dose. Sensitization describes the opposite situation, wherein repeated drug administration elicits increasing effects. Dependence refers to an altered physiological state that necessitates the continued administration of the abused drug to prevent the appearance of a withdrawal syndrome. Withdrawal is characterized by psychological and perhaps physical disturbances when the abused drug is withdrawn. The goal of this chapter is to review the evidence for a role of G proteins in these phenomena.