{"doi":"10.3389/fpsyt.2023.1252507","title":"Editorial: Molecular aspects of compulsive drug use","abstract":"Drug addiction is a complex psychiatric disorder defined by a compulsion to seek and take the drug, losing control over intake, and continuing to take the drug despite negative consequences.The inability to limit drug consumption leads to relapse and failure in treatment, thus understanding the underlying molecular mechanisms that contribute to compulsive drug seeking and taking is critical to developing efficient treatments. The medical term for drug addiction is substance use disorder (SUD), which is defined by an individual having two or more of the 11 criteria that are outlined in the 5 th edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (American Psychiatric Association, 2013).Several criteria for SUD encompass a wide range of indicators that associate with compulsive drug use. These criteria specifically focus on two key aspects: risky use and social impairment.Risky use is characterized by recurrent substance use in physically unsafe environments and persistent substance use despite awareness of potential physical or psychological harm. Social impairment criteria encompass the inability to fulfill major obligations at work, school, or home; continued use of the substance despite significant social or interpersonal problems; and reduction or discontinuation of recreational, social, or occupational activities due to substance use. Despite significant research efforts, the precise molecular mechanisms underlying compulsive drug use in remain largely unknown. However, gaining a deeper understanding of the neurobiological mechanisms that underly compulsive drug taking could lead to novel pharmacological and psychological tools to treat SUD. The papers in this Research Topic, \"Molecular Aspects of Compulsive Drug Use\" provide new knowledge towards achieving this goal. This collection contains preclinical and clinical studies on three different substances: alcohol, cocaine, and methamphetamine. Three of the papers on this topic also have a secondary emphasis on sex differences in compulsive drug use. Women have historically been underrepresented in behavioral neuroscience research but like men, also suffer from SUD. Understanding differences in neurobiology that contribute to sex differences in compulsive drug use will aid in developing effective treatments for both sexes.As in any type of behavioral neuroscience research, the development of animal models is an essential first step to understanding the underlying molecular neurobiology. The review article by De Oliveira Sergio, Frasier, and Hopf (Thatiane De Oliveira Sergio, Frasier, & Hopf, 2023) compares two commonly used animal models of compulsive-like alcohol drinking (CLAD): foot shock-resistant operant ethanol self-administration and quinine-resistant alcohol drinking in the home cage. In the foot shock procedure, animals must overcome a painful foot shock to obtain an alcohol reward. In the quinine-resistant alcohol drinking procedure, bitter-tasting quinine is added to the alcohol solution; animals exhibit CLAD when they continue to consume alcohol even though it contains quinine. Previous studies by the Hopf lab (T. De Oliveira Sergio et al., 2021;Seif et al., 2013) have demonstrated that prefrontal cortex and anterior insular cortex (AIC) circuits are involved in CLAD using both the foot shock-and quinine-resistant models of alcohol drinking. In the review article (Thatiane De Oliveira Sergio et al., 2023), they argue for the utility of the quinine-resistant alcohol consumption model, given its ease of use, ability to test multiple doses of quinine and perform repeated testing within subjects. The article also describes the current state of the literature on sex differences in aversion-resistant alcohol consumption.They conclude that many, but not all, studies have shown that female rats and mice are more aversion-resistant than males in the quinine-and foot shock-resistant models of CLAD. 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Lasek","orcid":"0000-0002-7099-2442","position":0,"is_corresponding":true}],"reference_count":7,"raw_metadata":null,"created_at":"2026-07-19T01:21:31.144858Z","pmid":"37559919","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}