ReviewFrontiers in behavioral neuroscience2020
Sex Differences and the Role of Estradiol in Mesolimbic Reward Circuits and Vulnerability to Cocaine and Opiate Addiction.
Review in Frontiers in behavioral neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.
- The association between age at menarche and depression: A systematic review and meta-analysis with meta-regression.Clinics (Sao Paulo, Brazil) · 2025Pooled it
- The Role of Kappa-Opioid Receptor/Dynorphin System in Modulating Neural-Circuits of Depression and Anxiety-A Review.Journal of cellular and molecular medicine · 2026Review
- Adolescent social isolation promotes oxycodone consumption and augments mu opioid receptor responsiveness in the ventral pallidum.Addiction neuroscience · 2026Article
- The Endogenous Opioid System in Compulsive Eating.Brain sciences · 2026Review
- Impulse control disorders and their relationship with psychopathology in patients treated with cabergoline for hyperprolactinaemia.Pituitary · 2026Article
- Sex and ovarian hormone cycles alter effects of stimulant drugs on mouse dopaminergic signaling.The Journal of clinical investigation · 2026Article
- Affective Sensitivity to Ovarian Steroid Hormone Flux Across the Menstrual Cycle: Manifestations and Biopsychosocial Risk Factors.Annual review of clinical psychology · 2026Review
- The role of nucleus accumbens Fos expression in sex-dependent cocaine-induced locomotion, cocaine self-administration, and primed cocaine seeking in rats.Behavioural brain research · 2026Article
- Not just neurons: glial mechanisms driving sex-specific vulnerability to withdrawal and relapse in substance use disorder.Frontiers in neuroendocrinology · 2026Review
- Remifentanil self-administration promotes circuit- and sex-specific adaptations within the prefrontal-accumbens pathways.bioRxiv : the preprint server for biology · 2026Article
- Beyond dopamine: Broader neuromodulatory contributions in sign- and goal-tracking.Psychopharmacology · 2026Review
- Electrophysiological sexual dimorphism as an early risk marker of alcohol use in adolescence: A longitudinal neuroimaging study.Addiction (Abingdon, England) · 2026Article
- Sex, social rank, and nicotine co-administration shape cocaine- and cocaethylene-induced reinstatement in monkeys.Frontiers in behavioral neuroscience · 2026Article
- Remifentanil self-administration promotes circuit- and sex-specific adaptations within the prefrontal-accumbens pathways.Frontiers in cellular neuroscience · 2026Article
- Cocaine sensitization and accumbens shell plasticity depend on biological sex and gonadal hormones in C57BL/6J mice.bioRxiv : the preprint server for biology · 2025Article
- Oxycodone self-administration and drug-primed responding in male and female squirrel monkeys: Effects of alternative reinforcer availability.The Journal of pharmacology and experimental therapeutics · 2025Article
- Prior adolescent oxycodone exposure enhances pain sensitivity following chronic intermittent ethanol in adult female mice.Physiology & behavior · 2025Article
- Estradiol, via estrogen receptor β signaling, mediates stress-susceptibility in the male brain.Molecular psychiatry · 2025Article
- Assessment of abuse potential of furanylfentanyl and tetrahydrofuranylfentanyl.Psychopharmacology · 2025Article
- Social rank modulates methamphetamine-seeking in dominant and subordinate male rodents via distinct dopaminergic pathways.Nature neuroscience · 2025Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Although both men and women become addicted to drugs of abuse, women transition to addiction faster, experience greater difficulties remaining abstinent, and relapse more often than men. In both humans and rodents, hormonal cycles are associated with females' faster progression to addiction. Higher concentrations and fluctuating levels of ovarian hormones in females modulate the mesolimbic reward system and influence reward-directed behavior. For example, in female rodents, estradiol (E2) influences dopamine activity within the mesolimbic reward system such that drug-directed behaviors that are normally rewarding and reinforcing become enhanced when circulating levels of E2 are high. Therefore, neuroendocrine interactions, in part, explain sex differences in behaviors motivated by drug reward. Here, we review sex differences in the physiology and function of the mesolimbic reward system in order to explore the notion that sex differences in response to drugs of abuse, specifically cocaine and opiates, are the result of molecular neuroadaptations that differentially develop depending upon the hormonal state of the animal. We also reconsider the notion that ovarian hormones, specifically estrogen/estradiol, sensitize target neurons thereby increasing responsivity when under the influence of either cocaine or opiates or in response to exposure to drug-associated cues. These adaptations may ultimately serve to guide the motivational behaviors that underlie the factors that cause women to be more vulnerable to cocaine and opiate addiction than men.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.