Estrogen control of central neurotransmission: Effect on mood, mental state, and memory
- 644 Downloads
1. Estrogen exerts profound effects on mood, mental state and memory by acting on both “classical” monoamine and neuropeptide transmitter mechanisms in brain. Here we review an example of each type of action.
2. With respect to the effect of estrogen on central monoamine neurotransmission, low levels of estrogen in women are associated with the premenstrual syndrome, postnatal depression and post-menopausal depression. Sex differences in schizophrenia have also been attributed to estrogen. Previous studies have shown that estrogen stimulates a significant increase in dopamine2 (D2) receptors in the striatum. Here we show for the first time that estrogen also stimulates a significant increase in the density of 5-hydroxytryptamine2A (5-HT2A) binding sites in anterior frontal, cingulate and primary olfactory cortex and in the nucleus accumbens, areas of the brain concerned with the control of mood, mental state, cognition, emotion and behavior. These findings explain, for example, the efficacy of estrogen therapy or 5-HT uptake blockers such as fluoxetine in treating the depressive symptoms of the premenstrual syndrome, and suggest that the sex differences in schizophrenia may also be due to an action of estrogen mediated by way of 5-HT2A receptors.
3. With respect to the effect of estrogen on central neuropeptide transmission, estrogen stimulates the expression of the arginine vasopressin (AVP) gene in the bed nucleus of the stria terminalis (BNST) in rodents. This results in a 100-fold increase in AVP mRNA in the BNST and a massive increase in AVP peptide in the BNST and its projections to the lateral septum and lateral habenula. The BNST-AVP system enhances and/or maintains “social” or “olfactory” memory, and thus provides a powerful model for correlating transcriptional control of neuropeptide gene expression with behavior. Whether similar mechanisms operate in the human remain to be determined.
4. These two examples of the action of estrogen on central neurotransmission are discussed in terms of their immediate clinical importance for the treatment of depressive symptoms, their use as powerful models for investigations on the steroid control of central neurotransmitter mechanisms, and the role of estrogen as “Nature's” psychoprotectant.
Key wordsestrogen as psychoprotectant estradiol-17ß testosterone aromatase serotonin 5-hydroxytryptamine 5-hydroxytryptamine2 receptors cerebral cortex nucleus accumbens arginine vasopressin bed nucleus of the stria terminalis social memory psychosis depression premenstrual syndrome postnatal depression schizophrenia mania Tourette's syndrome
Unable to display preview. Download preview PDF.
- Aghajanian, G. K., Sprouse, J. S., and Rasmussen, K. (1987). Physiology of the midbrain serotonin system. InPsychopharmacology: The Third Generation of Progress (H. Y. Meltzer, Ed.). Raven Press, New York, pp. 141–149.Google Scholar
- Appel, N. M., Mitchell, W. M., Garlick, R. K., Glennon, R. A., Teitler, M., and De Souza, E. B. (1990). Autoradiographic characterization of (±)-1-(2.5-dimethoxy-4-[125l]iodophenyl)-2-aminopropane ([125l]DOI) binding to 5-HT2 and 5-HT1C receptors in rat brain.J. Pharmacol. Exp. Ther. 255843–857.PubMedGoogle Scholar
- Ashcroft, G. W., Eccleston, D., Murray, L. G., Glen, A. I. M., Crawford, T. B. B., Pullar, I. A., Shields, P. J., Walter, D. S., Blackburn, I. M., Connechan, J., and Lonergan, M. (1972). Modified amine hypothesis for the aetiology of affective illness.Lancet 3573–577.Google Scholar
- Bleuler, E. (1950).Dementia Praecox or the Group of Schizophrenias International Universities Press, New York.Google Scholar
- Bluthé, R. M., Suarez, S., Fink, G., Roques, B., and Dantzer, R. (1993b). Social recognition in mice is modulated by androgen-dependent vasopressinergic and cholecystokininergic neurotransmission. Proceedings of the Society for Neuroscience 23rd Annual Meeting, Washington, DC. p. 73.6.Google Scholar
- Dalton, K. (1959). Menstruation and acute psychiatric illnesses.Br. Med. J. 1148–149.Google Scholar
- Duinkerke, S. J., Botter, P. A., Jansen, A. A. I., van Dongen, P. A. M., van Haaften, A. J., Boom, A. J., van Laarhoven, J. H. M., and Busard, H. L. S. M. (1993). Ritanserin, a selective 5-HT(2/1C) antagonist, and negative symptoms in schizophrenia. A placebo-controlled double-blind trial.Br. J. Psychiatry 163451–455.PubMedGoogle Scholar
- Edwards, J. G. (1994). Risperidone for schizophrenia.Br. Med. J. 3081311–1312.Google Scholar
- Everett, J. W. (1988). Pituitary and hypothalamus: Perspectives and overviews. InThe Physiology of Reproduction (E. Knobil and J. Neil, Eds.), Raven Press, New York, pp. 1143–1159.Google Scholar
- Fink, G. (1994). Molecular principles from neuroendocrine models: Steroid control of central neurotransmission. InProgress in Brain Research—Neuroscience: From the Molecular to the Cognitive (F. Bloom, Ed.), Elsevier, Amsterdam, pp. 139–147.Google Scholar
- James, M. D., Lane, S. M., Hole, D. R., and Wilson, C. A. (1989). Hypothalamic sites of action of the dual effect of 5-HT on female sexual behaviour in the rat. InBehavioral Pharmacology of 5-HT (P. Bevan, A. R. Cools, and T. Archer, Eds.), Lawrence Erlbaum Associates, Hillsdale, NJ, pp. 73–77.Google Scholar
- Kaplan, H. I., and Sadock, B. J. (1985).Comprehensive Textbook of Psychiatry Williams and Wilkins, Baltimore, MD.Google Scholar
- Kraepelin, E. (1971).Dementia Praecox and Paraphrenia Krieger, Huntington, NY.Google Scholar
- Leckman, J. F., and Scahill, L. (1990). Possible exacerbation of tics by androgenic steroids.N. Engl. J. Med. 3221674.Google Scholar
- Leysen, J. E., Van Gompel, P., Verwimp, M., and Niemegeers, C. J. E. (1983). Role and localisation of serotonin (S2)-receptor binding sites: Effects of neuronal lesions. InCNS Receptors—From Molecular Pharmacology to Behaviour (P. Mandel and F. V. de Feudis, Eds.), Raven Press, New York, pp. 373–383.Google Scholar
- Leysen, J. E., Janssen, P. M. F., Gommeren, W., Wynants, J., Pauwels, P. J., and Janssen, P. A. J. (1992).In vitro andin vivo receptor binding and effects on monoamine turnover in rat brain regions of the novel antipsychotics risperidone and ocaperidone.Mol. Pharmacol. 41494–508.PubMedGoogle Scholar
- MacKinnon, P. C. B., and MacKinnon, I. L. (1956). Hazards of the menstrual cycle.Br. Med. J. 1555.Google Scholar
- McEwen, B. S., Biegon, A., Rainbow, T. C., Paden, C., Snyder, L., and DeGroff, V. (1981). The interaction of estrogens with intracellular receptors and with putative neurotransmitter receptors: Implications for the mechanisms of activation of regulation of sexual behavior and ovulation. InSteroid Hormone Regulation of the Brain (K. Fuxe, J. A. Gustafsson, and L. Wetterberg, Ed.), Pergamon, New York, pp. 15–29.Google Scholar
- Nauta, W. J. H. (1963). Central nervous organization and the endocrine motor system. InAdvances in Neuroendocrinology (A. V. Nalbandov, Ed.), University of Illinois Press, Urbana, pp. 5–12.Google Scholar
- O'Brien, P. M. S. (1993). Helping women with premenstrual syndrome.Br. Med. J. 3071471–1475.Google Scholar
- Pfaff, D. W. (1980).Estrogens and Brain Function Springer, New York.Google Scholar
- Rosie, R., Wilson, H., and Fink, G. (1993). Testosterone induces an all-or-none, exponential increase in arginine vasopressin mRNA in the bed nucleus of stria terminalis of thehypogonadal mouse.Mol. Cell. Neurosci. 4121–126.Google Scholar
- Strange, P. G. (1994). Dopamine D4 receptors: curioser and curioser.Trends Phamacol. Sci. 15317–319.Google Scholar
- Studd, J., and Zamblera, D. (1994). Premenstrual depression.Focus Depress. 26–9.Google Scholar
- Sumner, B. E. H., and Fink, G. (1993). Effects of acute estradiol on 5-hydroxytryptamine and dopamine receptor subtype mRNA expression in female rat brain.Mol. Cell. Neurosci. 483–92.Google Scholar
- Sumner, B. E. H., and Fink, G. (1995a). Estrogen increases the density of 5-HT2A receptors in cerebral cortex and nucleus accumbens in the female rat.J. Steroid Biochem. Mol. Biol. 545–20.Google Scholar
- Sumner, B. E. H., and Fink, G. (1995b). Oestradiol-17ß in its positive feedback mode significantly increases 5-HT2A receptor density in the frontal, cingulate and piriform cortex of the female rat.J. Physiol. 483.P:52P.Google Scholar
- Sumner, B. E. H., Rosie, R., and Fink, G. (1992). Relative density of 5-hydroxytryptamine receptor subtype mRNAs in female rat neuroendocrine brain determined byin situ hybridization histochemistry.Mol. Cell. Neurosci. 3215–223.Google Scholar
- Wieck, A., Kumar, R., Hirst, A. D., Marks, M. N., Campbell, I. C., and Checkley, S. A. (1991). Increased sensitivity of dopamine receptors and recurrence of affective psychosis after childbirth.Br. Med. J. 303613–616.Google Scholar
- Wilson, J. D., and Foster, D. W. (Eds.) (1992).Williams Textbook of Endocrinology 8th ed., W B Saunders, Philadelphia, 1712.Google Scholar
- Wright, W. E. (1992). Muscle basic helix-loop-helix proteins and the regulation of myogenesis.Curr. Opin. Gen. Dev. 2243–248.Google Scholar