Evidence That 5-HT2AReceptors in the Hypothalamic Paraventricular Nucleus Mediate Neuroendocrine Responses to (−)DOI
Open accessAbstract
The present study determined whether the serotonin2A (5-HT2A) receptors in the hypothalamic paraventricular nucleus mediate the neuroendocrine responses to a peripheral injection of the 5-HT2A/2C receptor agonist (-)DOI [(-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane]. The 5-HT2A receptor antagonist MDL100,907 ((+/-)-alpha(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinemethanol), the 5-HT2C receptor antagonist SB-242084 (6-chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-indoline), or vehicle were microinjected bilaterally through a chronically implanted double-barreled cannula into the hypothalamic paraventricular nucleus 15 min before a peripheral injection of (-)DOI in conscious rats. (-)DOI significantly elevated plasma levels of oxytocin, prolactin, ACTH, corticosterone, and renin. Neither the 5-HT2A receptor antagonist nor the 5-HT2C receptor antagonist, injected alone, altered the basal levels of these hormones. MDL100,907 (0.748, 7.48, and 18.7 nmol) dose dependently inhibited the (-)DOI-induced increase in all of the hormones except corticosterone. In contrast, SB-242084 (10 nmol) did not inhibit (-)DOI-increased hormone levels. To confirm the presence of 5-HT2A receptors in the hypothalamic paraventricular nucleus, 5-HT2A receptors were mapped using immunohistochemistry. Densely labeled magnocellular neurons were observed throughout the anterior and posterior magnocellular subdivisions of the hypothalamic paraventricular nucleus. Moderately to densely labeled cells were also observed in parvicellular regions. Thus, it is likely that 5-HT2A receptors are present on neuroendocrine cells in the hypothalamic paraventricular nucleus. These data provide the first direct evidence that neuroendocrine responses to a peripheral injection of (-)DOI are predominantly mediated by activation of 5-HT2A receptors in the hypothalamic paraventricular nucleus.
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- Authors
- Zhang, Y., Damjanoska, K. J., Carrasco, G. A., Dudas, B., D'Souza, D. N., Tetzlaff, J., Garcia, F., Hanley, N. R. S., Scripathirathan, K., Petersen, B. R., Gray, T. S., Battaglia, G., Muma, N. A., & Van de Kar, L. D.
- Affiliations
- Loyola University Chicago (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-11-01
- Volume
- 22
- Issue
- 21
- Pages
- 9635-9642
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6758011
- OpenAlex
- W1891846574
- Cited by
- 107
- References
- 63
- Citations by year
- 2025: 6 · 2024: 5 · 2023: 5 · 2022: 5 · 2021: 1 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 5 · 2016: 5 · 2015: 1 · 2014: 5 · 2013: 5 · 2012: 6
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- KU ScholarWorks (University of Kansas) (submittedVersion, other-oa)
- Funders
- National Aeronautics and Space Administration
- Ames Research Center
- U.S. Public Health Service
- National Institute on Drug Abuse (R01DA013669, DA 13669)
- National Institute of Neurological Disorders and Stroke (NS34153, R56NS034153, R01NS034153)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- serotonin, paraventricular nucleus, hypothalamus, digital object identifiers, 5-HT2C receptor, SB242084, neuroendocrine response, oxytocin, prolactin, ACTH, corticosterone, renin, magnocellular neurons
- MeSH terms
- Adrenocorticotropic Hormone, Amphetamines, Animals, Corticosterone, Dose-Response Relationship, Drug, Fluorobenzenes, Immunohistochemistry, Male, Microinjections, Neurosecretory Systems, Oxytocin, Paraventricular Hypothalamic Nucleus, Piperidines, Prolactin, Receptors, Serotonin, Renin, Serotonin Antagonists, Rats, Sprague-Dawley, Serotonin Receptor Agonists, Receptor, Serotonin, 5-HT2A, Rats
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