Abstract

Heightened anxiety and sensitivity to stress following chronic cocaine use are likely to increase an individual's susceptibility for relapse to drug-seeking behavior. Thus, it is important to investigate the neural mechanisms responsible for the regulation of anxiety during cocaine withdrawal and stress-induced relapse in order to identify potential targets for pharmacological intervention. This chapter will address the involvement of several neurotransmitter systems in regulating anxiety during cocaine withdrawal and stress-induced relapse mechanisms. The distinct roles of the dopamine, serotonin, corticotropin releasing factor, norepinephrine, and opioid systems in regulating the negative consequences of cocaine withdrawal and the effects of stress in eliciting relapse to drug use will be discussed. In addition, a section detailing the potential role of other neuropeptides like cholecystokinin and neuropeptide Y in cocaine withdrawal-induced anxiety and stress-induced relapse is included. It is important to consider the roles of these brain-signaling systems separately, as well as integrated in a network that functions in regulating anxiety during cocaine withdrawal and the effects of stress on drug abuse and relapse to drug use. By targeting these regulatory mechanisms, potential pharmacological targets may be identified in support of the prevention of relapse to drug use.

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