Possible Mechanisms Underlying the Effects of Glucagon-Like Peptide-1 Receptor Agonist on Cocaine Use Disorder

Changliang Zhu; Hailiang Li; Xuerui Kong; Yezhong Wang; Tao Sun; Feng Wang

doi:10.3389/fphar.2022.819470

Possible Mechanisms Underlying the Effects of Glucagon-Like Peptide-1 Receptor Agonist on Cocaine Use Disorder

Front Pharmacol. 2022 Mar 1:13:819470. doi: 10.3389/fphar.2022.819470. eCollection 2022.

Authors

Changliang Zhu^{1

2

3}, Hailiang Li^{1

2

3}, Xuerui Kong^{2

3}, Yezhong Wang⁴, Tao Sun^{1

2

3}, Feng Wang^{2

3

5}

Affiliations

¹ Department of Neurosurgery, General Hospital of Ningxia Medical University, Yinchuan, China.
² Ningxia Key Laboratory of Cerebrocranial Disease, Yinchuan, China.
³ Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, China.
⁴ Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
⁵ Department of Neurosurgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Abstract

Cocaine use disorder (CUD) is a major public health challenge with a high relapse rate and lack of effective pharmacotherapies; therefore, there is a substantial need to identify novel medications to treat this epidemic. Since the advent of glucagon-like peptide-1 (GLP-1) receptors (GLP-1Rs) agonists (GLP-1RAs), their potential has been extensively explored and expanded. In this review, we first summarized the biological effects of GLP-1, GLP-1Rs, and GLP-1RAs. Subsequently, the recent literature examining the behavioral effects and the possible pharmacological mechanisms of GLP-1RAs on CUD was reviewed. Increasing preclinical evidence suggests that GLP-1RAs are promising in regulating dopamine release, dopamine transporter (DAT) surface expression and function, mesolimbic reward system and GABAergic neurons, and maladaptive behaviors in animal models of self-administration and conditioned place preference. In addition, the emerging role of GLP-1RAs in inhibiting inflammatory cytokines was reported. These findings indicate that GLP-1RAs perform essential functions in the modulation of cocaine-seeking and cocaine-taking behaviors likely through multifaceted mechanisms. Although the current preclinical evidence provides convincing evidence to support GLP-1RA as a promising pharmacotherapy for CUD, other questions concerning clinical availability, impact and specific mechanisms remain to be addressed in further studies.

Keywords: GABA; arachidonic acid; cocaine; dopamine; glucagon-like peptide-1 receptor agonist; glutamate; neuroinflammation.

Publication types

Review