Amygdala Mechanisms of Pavlovian Psychostimulant Conditioning and Relapse

Abstract

Psychostimulant addiction often consists of periods of sustained drug abstinence disrupted by periods of relapse and renewed heavy drug use. Prevention of relapse remains the greatest challenge to the successful treatment of drug addiction. Drug-associated cues are a primary trigger for relapse, as they can elicit intense craving for the drug. These cues become associated with the drug reward through Pavlovian learning processes that develop over multiple drug–cue pairings. The amygdala (AMY) is critical for such drug-related learning. Intrinsic and extrinsic circuitry position the AMY to integrate cue and drug-related information and influence drug-seeking and drug-taking behaviors. Animal models of conditioned drug reward, drug use, and relapse have confirmed the necessary role of the AMY for drug conditioned cues to control motivated behavior. Neurons within the AMY are responsive to the primary effects of psychostimulants, and more critically, they also respond to the presentation of drug-associated cues. The mechanisms by which conditioned cues come to influence drug-seeking behavior likely involve long-term plasticity and neuroadaptations within the AMY. A greater understanding of the associative learning mechanisms that depend upon the AMY and related limbic and cortical structures, and the process by which drug cues come to gain control over behavior that maintains the addictive state, will facilitate the development of more effective addiction treatments.