About this Research Topic

Background

Substance use disorders have persisted as a major public health issue for decades, but the alarming rise of fatal overdoses in recent years has highlighted a need for improved pharmacological and/or behavioral therapeutic strategies. Substance use disorders are challenging to overcome due in part to the high risk for relapse that can endure over prolonged periods of abstinence. However, the neurobiological mechanisms and neural circuits underlying drug-seeking are not completely understood, nor is the manner by which they are influenced by other environmental or biological variables. In particular, the potential contribution of sex to drug-seeking and its underlying neurobiology has not been thoroughly investigated. Accumulating evidence from both human and animal models indicates that the occurrence of sex differences in drug-seeking behavior depends on a number of factors including the stimulus used to trigger drug-seeking, hormonal status of females, drug class, and drug exposure histories. Preliminary evidence also indicates that the underlying mechanisms of drug-seeking differ between males and females; notably, molecular differences have been reported between the sexes even in the absence of behavioral differences.

The primary purpose of this Research Topic is to enhance our understanding of sex-dependent differences in drug-seeking behavioral output and its underlying neurobiological mechanisms using contemporary animal models of drug relapse. Investigations of the role of sex on drug craving and relapse susceptibility in human populations will also be of interest. While articles that focus solely on the impact of sex on drug-seeking behavior will be considered, those which incorporate exploration into putative molecular, cellular, epigenetic, hormonal, or circuit-level mechanisms that mediate observed sex-dependent effects on behavior will be of particular interest. Secondarily, this Research Topic aims to resolve discrepancies in the literature regarding the role of sex in drug relapse by clarifying experimental conditions and parametric considerations that either enhance or dampen the detection of sex differences in relapse-like behavior. Identification of methodologies that reliably reveal sex differences in drug-seeking would represent a critical contribution to the preclinical addiction field and pave the way for important new discoveries.

Any article type that disseminates new information pertaining to the modulatory impact of sex on drug-seeking behavior will be considered, including (but not limited to) original research, brief research reports, reviews, mini-reviews, methods, and perspectives. The following list of subtopics and themes are especially invited:
• What mechanisms contribute to sex differences in drug-seeking (e.g., molecular, cellular, transcriptional, neural circuits, etc.)?
• Are there specific experimental conditions under which sex differences in drug-seeking are optimally detected?
• Are sex-dependent differences in drug-seeking generalized across drug classes or limited to specific drug classes (e.g., opioids, psychostimulants, alcohol, nicotine, etc.)?
• Are sex-dependent differences in drug-seeking generalized across triggering stimuli or limited to specific stimuli (e.g., drug prime, context, discrete cues, pharmacological and nonpharmacological stressors)?
• Do biological and/or behavioral markers of relapse vulnerability vary by sex?
• Do potential relapse-prevention pharmacotherapeutics show sex-dependent differences in efficacy?
• Is drug-seeking behavioral output dependent on hormonal fluctuations in females?

Keywords: sex differences, substance use disorder, addiction relapse, estrous cycle, drugs of abuse, incubation, craving, reinstatement, self-administration

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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