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Androgen actions on central serotonin neurotransmission: relevance for mood, mental state and memory.
Abstract
Sex steroids exert potent effects on mood and mental state in the human. Our previous experimental findings in female rats suggest that these effects may be mediated, in part, by the action of estrogen on the 5-hydroxytryptamine2A receptor (5-HT(2A)R) and serotonin transporter (SERT) in brain. Here we review our recent findings on the effect of acute (approximately 32 h) testosterone manipulation on central 5-HT(2A)R and SERT in male rats. Castration decreased while testosterone or estrogen, but not 5alpha-dihydrotestosterone (5alpha-DHT), increased significantly the content of 5-HT(2A)R mRNA and SERT mRNA in the dorsal raphe nucleus (DR) and the density of 5-HT(2A)R and SERT binding sites in higher centers of the brain. The lack of effect of 5alpha-DHT, a potent androgen which cannot be converted to estrogen, suggests that the action of testosterone depends upon its conversion to estrogen by aromatase. This may also explain why estrogen, but not testosterone or 5alpha-DHT, increased the density of 5-HT(2A)R binding sites in the caudate-putamen, a brain region where aromatase is scarce. The estrogen induction of SERT mRNA is most prominent in the rostral DR and this together with the correlation between sensitivity of DR serotonin neurons to estrogen and neurotoxic amphetamine derivatives provides a potential topochemical handle with which to investigate testosterone/estrogen regulation of SERT gene expression. These findings are discussed in relation to the possible role of…
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“Testosterone reduced total sleep time by direct central nervous system effects by altering serotonergic neurotransmission. [6]”
From Comparison of sleep in hypothyroid patients with normal controls (2017) · cites this paper as [6]
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“Although hypothyroidism has increased incidence in females, an equal gender distribution was opted to minimize the effect of sex hormones on sleep in this study.”
From Comparison of sleep in hypothyroid patients with normal controls (2017) · cites this paper as [6]
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Metadata
- Authors
- Fink, G., Sumner, B., Rosie, R., Wilson, H., & McQueen, J.
- Affiliations
- University of Edinburgh (GB)
- Corresponding author
- Fink, George
- ORCID
- Fink, George
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 1999-11
- Volume
- 105
- Issue
- 1
- Pages
- 53-68
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W2079234104
- Cited by
- 198
- References
- 98
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 2 · 2023: 6 · 2022: 6 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 2 · 2016: 8 · 2015: 9 · 2014: 6 · 2013: 7 · 2012: 9
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- testosterone, estrogen, 5-HT2A receptor, serotonin transporter, dorsal raphe nucleus, aromatase, sex steroids, mood disorders, schizophrenia, Alzheimer's disease, memory, caudate-putamen, amphetamine neurotoxicity, gene expression regulation
- MeSH terms
- Affect, Androgens, Animals, Arousal, Brain Mapping, Carrier Proteins, Caudate Nucleus, Estrogens, Female, Gene Expression Regulation, Humans, Male, Membrane Glycoproteins, Memory, Nerve Tissue Proteins, Synaptic Transmission, Putamen, Raphe Nuclei, Receptors, Serotonin, Serotonin, Sexual Behavior, Sexual Behavior, Animal, Membrane Transport Proteins, Receptor, Serotonin, 5-HT2A, Serotonin Plasma Membrane Transport Proteins, Rats
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