ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2018
17β-Estradiol Potentiates the Reinstatement of Cocaine Seeking in Female Rats: Role of the Prelimbic Prefrontal Cortex and Cannabinoid Type-1 Receptors.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.
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Who cites it
29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 39 citations in OpenAlex.
- The influence of sex and reproductive cycle on cocaine-induced behavioral and neurobiological alterations: a review.Experimental brain research · 2022Pooled it
- Sex Differences in Opioid and Psychostimulant Craving and Relapse: A Critical Review.Pharmacological reviews · 2022Pooled it
- Synaptic Actions of Estradiol in the Brain's Reward System: Linking Mechanisms to Behavior and Disease.Biological psychiatry global open science · 2026Review
- Drug self-administration in head-fixed mice.Nature protocols · 2026Review
- Threat Conditioning Prior to Cocaine or Sucrose Exposure Alters Reward-Seeking Behavior in a Sex-Dependent Manner.Psychiatry international · 2026Article
- A rat model of oral hormonal contraception: Effects on drug preference and gonadal function.Behavioral neuroscience · 2026Article
- Effect of acute treatment with the glucagon-like peptide-1 receptor agonist, liraglutide, and estrus phase on cue- and drug-induced fentanyl seeking in female rats.Behavioural pharmacology · 2025Article
- Estrogen receptor beta signaling enhances extinction memory recall for heroin-conditioned cues in a sex- and region-specific manner.Translational psychiatry · 2024Article
- Role of estrogen in sex differences in memory, emotion and neuropsychiatric disorders.Molecular biology reports · 2024Review
- Circulating ovarian hormones interact with protein interacting with C kinase (PICK1) within the medial prefrontal cortex to influence cocaine seeking in female mice.Hormones and behavior · 2023Article
- Learning processes in relapse to alcohol use: lessons from animal models.Psychopharmacology · 2023Review
- Sex differences and hormonal regulation of metabotropic glutamate receptor synaptic plasticity.International review of neurobiology · 2023Review
- Neural Mechanisms Mediating Sex Differences in Motivation for Reward: Cognitive Bias, Food, Gambling, and Drugs of Abuse.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- 5-HTFrontiers in behavioral neuroscience · 2022Article
- Consideration of sex as a biological variable in the translation of pharmacotherapy for stress-associated drug seeking.Neurobiology of stress · 2021Review
- Behavioral sex differences in cocaine and opioid use disorders: The role of gonadal hormones.Neuroscience and biobehavioral reviews · 2021Review
- Activation of G protein-coupled estradiol receptor 1 in the dorsolateral striatum enhances motivation for cocaine and drug-induced reinstatement in female but not male rats.Biology of sex differences · 2021Article
- Estradiol Regulation of the Prelimbic Cortex and the Reinstatement of Cocaine Seeking in Female Rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Neurochemical mechanisms and neurocircuitry underlying the contribution of stress to cocaine seeking.Journal of neurochemistry · 2021Review
- Sex differences in vulnerability to addiction.Neuropharmacology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Clinical observations imply that female cocaine addicts experience enhanced relapse vulnerability compared with males, an effect tied to elevated estrogen phases of the ovarian hormone cycle. Although estrogens can enhance drug-seeking behavior, they do not directly induce reinstatement on their own. To model this phenomenon, we tested whether an estrogen could augment drug-seeking behavior in response to an ordinarily subthreshold reinstatement trigger. Following cocaine self-administration and extinction, female rats were ovariectomized to isolate estrogen effects on reinstatement. Although neither peak proestrus levels of the primary estrogen 17β-estradiol (E2; 10 μg/kg, i.p., 1-h pretreatment) nor a subthreshold cocaine dose (1.25 mg/kg, i.p.) alone were sufficient to reinstate drug-seeking behavior, pretreatment with E2 potentiated reinstatement to the ordinarily subthreshold cocaine dose. Furthermore, E2 microinfusions revealed that E2 (5 μg/0.3 μl, 15-min pretreatment) acts directly within the prelimbic prefrontal cortex (PrL-PFC) to potentiate reinstatement. As E2 has been implicated in endocannabinoid mobilization, which can disinhibit PrL-PFC projection neurons, we investigated whether cannabinoid type-1 receptor (CB1R) activation is necessary for E2 to potentiate reinstatement. The CB1R antagonist AM251 (1 or 3 mg/kg, i.p., 30-min pretreatment) administered prior to E2 and cocaine suppressed reinstatement in a dose-dependent manner. Finally, PrL-PFC AM251 microinfusions (300 ng/side, 15-min pretreatment) also suppressed E2-potentiated reinstatement. Together, these results suggest that E2 can augment reactivity to an ordinarily subthreshold relapse trigger in a PrL-PFC CB1R activation-dependent manner.
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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.