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

• Type of Material: Article
• Authors: Britton R Barbee, Emory University; Shannon L Gourley, Emory University
• Language: English
• Date: 2022-06-01
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2024 Elsevier B.V.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.addicn.2022.100012
• Title of Journal or Parent Work: Addiction Neuroscience
• Volume: 2
• Keywords: withdrawal; anxiety-like behavior; abstinence; cocaine; stimulant
• Research Categories: Health Sciences, Public Health; Health Sciences, Pharmacology

Abstract

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.