Effect of alcohol use disorder on oxytocin peptide and receptor mRNA expression in human brain: a post-mortem case-control study
Open accessAbstract
Animal and human evidence supports a role for oxytocin in alcohol-seeking behaviors. There is interest, therefore, in targeting the oxytocin pathway as a new pharmacologic approach to treat alcohol use disorder. To this end, it is important to understand the effect of alcohol use disorder on endogenous oxytocin in brain regions that are relevant for the initiation and maintenance of alcohol use disorder. We examined human post-mortem brain tissue from males with alcohol use disorder (n=11) compared to nonalcohol dependent male controls (n=16). We a priori targeted five brain regions that in rodent studies, are projection areas for oxytocin neurons: nucleus accumbens, amygdala, hippocampus, ventral tegmental area and prefrontal cortex. Fold change in mRNA levels of oxytocin peptide and receptor were measured in each of the brain regions studied. Fold change for oxytocin peptide mRNA was significantly elevated in the prefrontal cortex of subjects with alcohol use disorder compared to controls (uncorrected p=0.0001; FDR-corrected p=0.001). For the entire sample of 27 subjects, there was a significant positive correlation between the fold change in oxytocin peptide mRNA in the prefrontal cortex and both daily alcohol intake (r 2=0.38; p=0.002) and drinks per week (r 2=0.24; p=0.02). Results are discussed in light of the previous animal and human literature on changes in the endogenous oxytocin system as an effect of chronic alcohol exposure.
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In males with alcohol use disorder (AUD), oxytocin peptide mRNA is significantly elevated in the prefrontal cortex compared with controls.
“In a postmortem study of males with AUD, oxytocin peptide mRNA was significantly elevated in the prefrontal cortex in subjects with AUD compared with controls (Lee et al., 2017).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Lee et al., 2017
Although OXTR mRNA can be measured in some portions of the human cortex, autoradiographic studies of OXTR binding have not generated complementary evidence of functional, cell-surface OXTR in these regions of the cortex in humans or in nonhuman primates.
“Although these studies and others59–61 indicate that OXTR mRNA can be measured in some portions of the human cortex, autoradiographic studies of OXTR binding have not generated complementary evidence of functional, cell-surface OXTR in these regions of the cortex in humans35 or in nonhuman primates39.”
From Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain (2018) · cites this paper as [59]
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- Authors
- Lee, M. R., Schwandt, M. L., Sankar, V., Suchankova, P., Sun, H., & Leggio, L.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Lee, Mary R.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 85
- Pages
- 14-19
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC12439254
- OpenAlex
- W2735888831
- Cited by
- 33
- References
- 34
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 10 · 2020: 5 · 2019: 2 · 2018: 4
- FWCI
- 4.31
- Type
- journal article
- Language
- en
- Open access
- green
- pmc.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (ZIAAA000218, R28AA012725)
- National Institute on Drug Abuse (ZIADA000635)
- 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
- alcoholism, oxytocin, oxytocin receptor, prefrontal cortex, nucleus accumbens, amygdala, hippocampus, ventral tegmental area, chronic ethanol exposure, alcohol consumption, postmortem brain
- MeSH terms
- Adult, Alcoholism, Autopsy, Humans, Male, Middle Aged, Oxytocin, RNA, Messenger, Tissue Banks, Case-Control Studies, Prefrontal Cortex, Receptors, Oxytocin
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