Brain systems in cocaine abstinence-induced anxiety-like behavior in rodents: A review

• Published in: Addiction neuroscience 2022-06, Vol.2, p.100012, Article 100012
• Main Authors: Barbee, Britton R., Gourley, Shannon L.
• Format: Article
• Language: English
• Subjects: abstinence; anxiety-like behavior; cocaine; stimulant; withdrawal
• ISSN: 2772-3925; 2772-3925
• DOI: 10.1016/j.addicn.2022.100012

Cocaine use disorder (CUD) is a significant public health issue that generates substantial personal, familial, and economic burdens. Still, there are no FDA-approved pharmacotherapies for CUD. Cocaine-dependent individuals report anxiety during withdrawal, and alleviation of anxiety and other negative affective states may be critical for maintaining drug abstinence. However, the neurobiological mechanisms underlying abstinence-related anxiety in humans or anxiety-like behavior in rodents are not fully understood. This review summarizes investigations regarding anxiety-like behavior in mice and rats undergoing cocaine abstinence, as assessed using four of the most common anxiety-related assays: the elevated plus (or its derivative, the elevated zero) maze, open field test, light-dark transition test, and defensive burying task. We first summarize available evidence that cocaine abstinence generates anxiety-like behavior that persists throughout protracted abstinence. Then, we examine investigations concerning neuropeptide, neurotransmitter, and neuromodulator systems in cocaine abstinence-induced anxiety-like behavior. Throughout, we discuss how differences in sex, rodent strain, cocaine dose and dosing strategy, and abstinence duration interact to generate anxiety-like behavior.