Neurobiology of relapse to alcohol in rats.

Relapse to alcohol use after prolonged withdrawal periods is the major problem in the treatment of alcohol dependence in humans. However, until recently, relatively few preclinical studies concentrated on the elucidation of the neurochemical events underlying relapse to alcohol. In this article we will review recent data from studies in which alcohol-deprivation and reinstatement models were used to determine the mechanisms underlying relapse to alcohol in rats. In the alcohol-deprivation model, the intake of alcohol is determined after prolonged periods of forced abstinence in drug-experienced rats. In the reinstatement model, the ability of acute non-contingent exposure to drug or non-drug stimuli to reinstate drug seeking is determined following training for drug self-administration and subsequent extinction of the drug-reinforced behavior. We will review studies, which used these preclinical models, on the effect of specific pharmacological agents on relapse to alcohol seeking induced by re-exposure to alcohol and to alcohol-associated cues and by exposure to stress. Subsequently, we will describe potential neuronal circuits that may underlie relapse to alcohol. Finally, future directions and clinical implications of the study of relapse to alcohol in laboratory animals will be discussed briefly.