Neurobehavioral aspects of the pharmacotherapy of alcohol dependence.

A neurobehavioral basis for the pharmacologic treatment of alcoholism is beginning to emerge. Preclinical and clinical findings have provided valuable information on which to build bridges of understanding regarding the biological causes and treatment of alcoholism. Reinforcement and stress reduction are prominent in the initiation of alcohol use, while neuroadaptation to chronic alcohol exposure and Pavlovian conditioning of alcohol-like effects appear to be involved in the development of alcohol dependence. Impulsivity may play a crucial role in the rapidity with which alcohol dependence develops. This article presents a model that attempts to integrate these neurobehavioral phenomena with neurochemical systems. The pharmacological agents that have been studied for the treatment of alcoholism are reviewed in the context of this model. While medications that affect the serotonin system have been the most widely studied for the treatment of alcoholism, their clinical effects have been modest or inconsistent. Medications that affect dopaminergic neurotransmission have received less research attention, and their potential clinical utility may be limited by their side effect profile. The most efficacious agents for the treatment of alcoholism have been the opiate antagonists, including naltrexone. Naltrexone recently received approval from the U.S. Food and Drug Administration for relapse prevention in alcoholism. A number of recent clinical and animal studies suggest potential mechanisms of action for opiate antagonists in the treatment of alcoholism. Knowledge in this field is advancing rapidly. Developments in neurobiology, coupled with improvements in both animal models of alcohol self-administration and clinical trial methodology will surely further our understanding of the pathophysiology and pharmacotherapy of alcohol dependence.