Serotonin neurobiology in cocaine use disorder

Abstract Cocaine misuse can escalate, leading to compulsive drug-taking and drug-seeking which characterizes the development of cocaine use disorder (CUD), an acquired brain disorder with clinically significant impairment. Cocaine binds to the serotonin (5-hydroxytryptamine; 5-HT) transporter, inhibits reuptake, and increases extracellular 5-HT efflux within limbic-corticostriatal circuitry involved in CUD neurobiology. The role of 5-HT in the in vivo effects of cocaine depends upon the 5-HT receptors and downstream signaling webs triggered. Multiple 5-HT receptor mechanisms and perturbations in the balance of serotonergic control contribute to basal states of vulnerability to CUD processes as well as the altered neurobiological states that drive the transition toward CUD and promote relapse. This review emphasizes the role of 5-HT and its receptor proteins and the implications of current findings to the future of therapeutics to enhance recovery and extend abstinence from CUD.