CNS region-specific oxytocin receptor expression: importance in regulation of anxiety and sex behavior
Open accessAbstract
The oxytocin receptor (OTR) is differentially expressed in the CNS. Because there are multiple mechanisms by which the OTR can be transcriptionally induced, we hypothesized that differences in OTR expression may be explained by activation of distinct signal transduction pathways and may be critical for the control of anxiety and sex behaviors. To determine the regulation and functional significance of this expression, we infused female rats with modifiers of protein kinases before assaying for behavior and oxytocin receptor binding. In the ventromedial nucleus of the hypothalamus (VMH), estrogen-dependent induction of oxytocin receptors required protein kinase C activation, and oxytocin infused here promoted female sex behavior but had no effect on anxiety. In contrast, dopamine controlled tonic oxytocin receptor expression in the central nucleus of the amygdala (cAmyg) through activation of protein kinase A, and oxytocin infused here was anxiolytic but had no effect on female sex behavior. Therefore, we have identified brain region-specific regulation of the OTR in the VMH and cAmyg. Distinct signal transduction pathways regulating receptor expression and binding in each brain region may mediate in part the ability of oxytocin to exert these differential behavioral effects.
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Effects of a single neuropharmacological challenge might differ considerably from endogenous OT mechanisms.
“effects of a single neuropharmacological challenge might differ considerably from endogenous OT mechanisms”
From Sex-specific effects of intranasal oxytocin on autonomic nervous system and emotional responses to couple conflict (2013) · cites this paper as Bale et al., 2001
The paper reports behavioral effects of experimentally infused oxytocin in the Open-field test and Experiment II, and discusses region-specific receptor regulation. Searches for endogenous oxytocin and for a comparison between pharmacological challenges and natural signaling found no passage making the claimed comparison; the indexed passages provide no page numbers. (LLM, conf=0.73)
Experimental — accuracy not yet measuredNo effects of oxytocin on anxiety were observed in the elevated plus maze test in our studies and those of Bale et al. (2001).
“no effects of oxytocin on anxiety were observed in the elevated plus maze test in our studies (unpublished data) and those of Bale et al. (2001).”
From Evidence for the existence of facilitatory interactions between the dopamine D2 receptor and the oxytocin receptor in the amygdala of the rat relevance for anxiolytic actions (2023) · cites this paper as Bale et al., 2001
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“Moreover, effects of a single neuropharmacological challenge might differ considerably from endogenous OT mechanisms, which are modulated by number and sensitivity of OT receptors in different areas of the CNS (Bale et al., 2001; Landgraf and Neumann, 2004).”
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- Authors
- Bale, T. L., Davis, A. M., Auger, A. P., Dorsa, D. M., & McCarthy, M. M.
- Affiliations
- University of Washington (US)
- University of Maryland, Baltimore (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-04-01
- Volume
- 21
- Issue
- 7
- Pages
- 2546-2552
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6762393
- OpenAlex
- W1948173875
- Cited by
- 446
- References
- 40
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 15 · 2023: 11 · 2022: 18 · 2021: 18 · 2020: 25 · 2019: 15 · 2018: 16 · 2017: 27 · 2016: 19 · 2015: 26 · 2014: 24 · 2013: 19 · 2012: 21
- FWCI
- 23.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Framingham State University Digital Repository (Framingham State University) (submittedVersion)
- Funders
- U.S. Public Health Service
- National Institute of Mental Health (R29MH052716, MH 52716, R01MH052716)
- National Institute of General Medical Sciences (T32-GM07270, T32GM007270)
- National Institute of Neurological Disorders and Stroke (NS-20311, R01NS020311)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- oxytocin receptor, anxiety, ventromedial hypothalamus, central amygdala, protein kinase C, protein kinase A, dopamine, signaling pathways
- MeSH terms
- Animals, Anxiety, Brain, Female, Oxytocin, Protein Kinase C, Sexual Behavior, Animal, Signal Transduction, Rats, Sprague-Dawley, Cyclic AMP-Dependent Protein Kinases, Receptors, Oxytocin, Rats
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