Oxytocin attenuates stress-induced reinstatement of alcohol seeking behavior in male and female mice
Open accessAbstract
Rationale The neuropeptide oxytocin (OXT) has emerged as a potential therapeutic intervention in the treatment of both alcohol use disorder (AUD) and stress-related psychiatric illnesses. Objectives The present study evaluates the effects of systemically administered (intraperitoneal (i.p.)) OXT treatment on alcohol relapse-like behavior in male and female mice. Methods Adult male and female C57BL/6J mice were trained to lever respond in operant conditioning chambers for alcohol in daily self-administration sessions. Once lever responding and alcohol intake stabilized, mice were tested under extinction conditions for 14 days before reinstatement testing. All mice underwent stress-induced reinstatement testing using either predator odor (2,3,5-trimethyl-3-thiazoline (TMT)) or the α-2 adrenergic receptor agonist yohimbine. In study 1, mice were exposed to TMT for 15 min and then immediately placed into operant conditioning chambers to examine alcohol-seeking behavior under extinction conditions. At 30 min prior to test session, separate groups of mice were injected with vehicle or OXT (0.1, 0.5, 1 mg/kg). In study 2, mice were injected with yohimbine (0.3, 0.625 mg/kg) 1 h prior to reinstatement testing. At 30 min post-yohimbine injection, mice are injected (i.p.) with vehicle or OXT (1 mg/kg). Results OXT attenuated alcohol-seeking behavior in a dose-related manner in male and female mice in response to acute challenge with a predator odor. Additionally, OXT administration produced a similar decrease in alcohol relapse-like behavior triggered by the pharmacological stressor yohimbine in both sexes. Conclusions Systemic oxytocin administration attenuates stress-induced reinstatement of alcohol seeking in male and female mice.
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- Authors
- King, C. E., & Becker, H. C.
- Affiliations
- Medical University of South Carolina (US)
- Corresponding author
- Becker, Howard C.
- Venue
- Psychopharmacology
- Published
- 2019-03-28
- Volume
- 236
- Issue
- 9
- Pages
- 2613-2622
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC6697557
- OpenAlex
- W2926109020
- Cited by
- 53
- References
- 70
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 8 · 2023: 8 · 2022: 12 · 2021: 10 · 2020: 9
- FWCI
- 9.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (F31 AA026483, U01 AA014095, U24 AA020929, P50 AA0107061)
- U.S. Department of Veterans Affairs (101BX000813)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- oxytocin, alcohol seeking, alcohol relapse, stress-induced reinstatement, alcoholism, yohimbine, alpha2-adrenoceptors, sex differences, extinction, self-administration
- MeSH terms
- Alcohol Drinking, Ethanol, Animals, Conditioning, Operant, Extinction, Psychological, Female, Male, Mice, Inbred C57BL, Oxytocin, Self Administration, Behavior, Addictive, Mice
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