Serotonin mediates CA1 spine density but is not crucial for ovarian steroid regulation of synaptic plasticity in the adult rat dorsal hippocampus
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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Neurotransmitters including norepinephrine, serotonin and glutamate, as well as stress-induced release of neuropeptides and steroids, can influence synapse number and function.
“Neurotransmitters, including norepinephrine,76, 77, 78 serotonin79, 80, 81 and glutamate,82,83 as well as stress-induced release of neuropeptides26,34,84,85 and steroids,86, 87, 88 can influence synapse number and function.”
From Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress (2014) · cites this paper as [79]
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Serotonin Deficits Modulate Hippocampal Plasticity
Foltran, R. B., & Soiza‐Reilly, M. (2026) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6c00120
- 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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