Cited by 45Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsNeurotransmitter Receptor Influence on Behavior

Serotonin mediates CA1 spine density but is not crucial for ovarian steroid regulation of synaptic plasticity in the adult rat dorsal hippocampus

Alves, Stephen E., Hoskin, Elena, Lee, Susan J., Brake, Wayne G., Ferguson, Deveroux, Luine, Victoria, Allen, Patrick B., Greengard, Paul, McEwen, Bruce S.·2002·Synapse

Abstract

The activity of the serotonin (5‐hydroxytryptamine, 5‐HT) system is sensitive to estradiol and progesterone. During the ovarian cycle, dendritic spines on CA1 pyramidal neurons of the dorsal hippocampus are increased by estradiol and later decreased by progesterone. We sought to determine whether 5‐HT is involved in maintaining CA1 spine density and/or in steroid regulation of synaptic plasticity in dorsal hippocampus. Ovariectomized rats were treated (sc) over 10 days with the tryptophan hydroxylase inhibitor parachlorophenylalanine (pCPA) to deplete 5‐HT, followed by estradiol benzoate on days 10 and 11. A subset of animals received progesterone on day 12. The day after the last treatment, rats were perfused and brains were processed for Golgi impregnation. Separate groups were processed for radioimmunocytochemistry (RICC) for the spine‐associated protein, spinophilin, or high‐performance liquid chromatography (HPLC) for monoamine analysis. Golgi and RICC data indicate that CA1 apical spine density was significantly decreased by pCPA (17–20%). Estradiol increased spine density in both saline‐ and pCPA‐treated rats compared to respective controls (30%); however, pCPA animals maintained significantly fewer spines. No differences in spine densities were observed between saline‐ and pCPA‐treated rats given estradiol and progesterone. Depletion of 5‐HT by pCPA was confirmed in the CA1 (−90%) and dorsal raphe (−80%) by HPLC analysis. While 5‐HT depletion was associated with a 57% decrease in CA1 norepinephrine (NE), there was no difference in dorsal raphe NE. Thus, whereas 5‐HT is involved in maintaining spine density in the adult female rat CA1, it is not crucial for steroid‐mediated plasticity. 5‐HT‐regulated spines/synapses may represent distinct populations from those modulated by estradiol and progesterone in dorsal hippocampus. Synapse 45:143–151, 2002. © 2002 Wiley‐Liss, Inc.

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Crossref · 10.1002/syn.10093

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Authors
Alves, S. E., Hoskin, E., Lee, S. J., Brake, W. G., Ferguson, D., Luine, V., Allen, P. B., Greengard, P., & McEwen, B. S.
Affiliations
  • Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
  • Rockefeller University (US)
  • Hunter College (US)
Corresponding author
Alves, Stephen E.
Venue
Synapse
Publisher
Wiley
Published
2002-05-29
Volume
45
Issue
2
Pages
143-151
ISSN
  • 0887-4476 (ISSN-L)
  • 1098-2396
OpenAlex
W2094936308
Cited by
45
References
66
Citations by year
2026: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2017: 3 · 2016: 1 · 2014: 3 · 2013: 1 · 2012: 3
FWCI
1.40
Type
journal article
Language
en
Open access
closed
Locations
  • Synapse (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r03mh059251-02)
  • National Institute of Mental Health (MH40899, MH59251, P01MH040899)
  • National Institute on Drug Abuse (DA10044, P01DA010044)
  • National Institute of Neurological Disorders and Stroke (R01NS007080, NS 07080)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
serotonin, dendritic spine density, CA1 pyramidal neurons, dorsal hippocampus, estradiol, progesterone, ovarian cycle, synaptic plasticity, p-chlorophenylalanine, tryptophan hydroxylase inhibition, norepinephrine, dorsal raphe nucleus, spinophilin, ovariectomized rats
MeSH terms
Neurabins, Animals, Chromatography, High Pressure Liquid, Estradiol, Female, Hippocampus, Histological Techniques, Immunohistochemistry, Microfilament Proteins, Nerve Tissue Proteins, Neuronal Plasticity, Neurons, Progesterone, Serotonin, Tryptophan Hydroxylase, Radioimmunodetection, Rats, Sprague-Dawley, Rats

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