Abstract
Previous studies have shown that adrenalectomy (ADX) increases the binding of3H-DPAT to 5-HT1A receptors in the hippocampus (HIP) and this effect is partially overcome by corticosterone (CORT) replacement. The present study investigated the time course of the effects of ADX with or without CORT replacement on serotonin (5-HT) pre- and postsynaptic systems in the HIP and dorsal raphe nucleus (DR) by quantitative autoradiography. In the HIP, ADX for 7, 10 or 14 days caused a significant increase in3H-DPAT binding in the CA1 region (pyramidal layer), CA2,3 region (molecular and pyramidal layers) and in the dentate gyrus (molecular and granular layers) which returned to control levels when measurements were made 35 days post-ADX. A decrease in3H-DPAT binding was observed 14 days after ADX in the DR but not in the median raphe nucleus (MR). Although replacement with CORT did not lead to a reversal in3H-DPAT binding at early time points, binding was restored to control levels 7–28 days after CORT replacement in all regions of the HIP. In the DR, CORT did not cause a reversal in3H-DPAT binding at any of the time points examined. In contrast to the effects seen on the 5-HT1A receptor subtype, no significant change was noted on the binding of3H-CN-IMI to uptake sites for 5-HT in the HIP or DR after ADX or CORT replacement. The results of this study indicate that long-term alterations in the HPA axis lead to changes in the 5-HT1A receptor system that are both region-specific and time-dependent.
Similar content being viewed by others
References
Andrade R, Nicoll R (1987) Novel anxiolytics discriminate between postsynaptic serotonin receptor mediating different physiological responses on single neurons of the rat hippocampus. Naunyn-Schmiedeberg's Arch Pharmacol 336:5–10
Biegon A, Rainbow TC, McEwen BS (1985) Corticosterone modulation of neurotransmitter receptors in rat hippocampus: a quantitative autoradiographic study. Brain Res 332:309–314
De Kloet ER, Kovacs GL, Szabo G, Telegdy G, Bohus B, Versteeg DHG (1982) Decreased serotonin turnover in the dorsal hippocampus of rat brain shortly after adrenalectomy: selective normalization after corticosterone substitution. Brain Res 239:659–663
De KIoet ER, Sybesma H. Reul HMHM (1986) Selective control by corticosterone of serotonin1 receptor capacity in raphe-hippocampal system. Neuroendocrinology 42:513–521
Feingold E, Seshadri SB, Tretiak O (1986) Hardware and software design considerations in engineering and image processing workstation: autoradiographic analysis with DUMAS and the BRAIN autoradiographic software package. In: McEachron, DL (ed) Experimental biology and medicine, vol 11. Functional mapping in biology and medicine. Karger, Basel, pp 175–203
Frazer A, Hensler JG (1990) 5-HT1A receptors and 5-HT1A-mediated responses: effect of treatments that modify serotonergic neurotransmission. Ann NY Acad Sci 600:460–475
Fuller RW (1990) Serotonin receptors and neuroendocrine responses. Neuropsychopharmacology 3:495–502
Fuller RW, Snoddy HD (1990) Serotonin receptor subtypes involved in the elevation of serum corticosterone concentration in rats by direct- and indirect-acting serotonin agonists. Neuroendocrinology 52:206–211
Fuxe K, Cintra A, Agnati LF, Harfstrand A, Wikstrom A-C, Okret S, Zoli M, Miller LS, Greene JL, Gustafsson J-A (1987) Studies on the cellular localization and distribution of glucocorticoid receptor and estrogen receptor immunoreactivity in the central nervous system of the rat and their relationship to the monoaminergic and peptidergic neurons of the brain. J Steroid Biochem 27:159–170
Geary II WA, Wooten GF (1983) Quantitative film autoradiography of opiate agonists and antagonists. J Pharmacol Exp Ther 225:234–240
Geary II WA, Wooten GF (1985) Quantitative film autoradiography for tritium: methodological consideration. Brain Res 337:99–108
Gilbert F, Brazel C, Tricklebank MD, Stahl SM (1988) Activation of the 5-HT1A receptor subtype increases plasma ACTH concentration. Eur J Pharmacol 147:431–439
Gothert M (1992) 5-Hydroxytryptamine receptors. Arzneimittelforschung 42:238–246
Gozlan H, Mestikawy SE, Pichat L, Glowinski J, Hamon M (1983) Identification of presynaptic serotonin autoreceptors using a new ligand:3H-PAT. Nature 305:140–142
Harfstrand A, Fuxe K, Cintra A, Agnati LF, Zini I, Wikstrom A-C, Okret S, Yu Z-Y, Goldstein M, Steinbusch H, Verhofstad A, Gustafsson J-A (1986) Glucocorticoid receptor immunoreactivity in monoaminergic neurons of rat brain. Proc Natl Acad Sci USA 83:9779–9783
Hensler JG, Kovachich GB, Frazer A (1991) A quantitative autoradiographic study of serotonin1A receptor regulation, effect of 5,7-dihydroxytryptamine and antidepressant treatments. Neuropsychopharmacology 4:131–144
Jacobs BL, Azmitia EC (1992) Structure and function of the brain serotonin system. Physiol Rev 72:165–229
Kovachich GB, Aronson CE, Brunswick DJ, Frazer A (1988) Quantitative autoradiography of serotonin uptake sites in rat brain using [3H]cyanoimipramine. Brain Res 454:78–88
Landfield P, Baskin R, Pitler T (1981) Brain-aging correlates: retardation by hormonal-pharmacological treatment. Science 241:581–585
Lesch KP, Lerer B (1991) The 5-HT receptor-G-protein-effector system complex in depression I. Effect of glucocorticoids. J Neural Transm 84:3–18
Lorens SA, Van de Kar LD (1987) Differential effects of serotonin (5-HT1A and 5-HT2) agonists and antagonists on renin and corticosterone secretion. Neuroendocrinology 45:305–310
Martire M, Navarra P, Pistritto G, Preziosi P (1988) Adrenal steroid-induced changes in rat hippocampus and hypothalamus. Pharmacol Res Commun 20:415–416
McEwen B, De Kloet ER, Rostene W (1986) Adrenal steroid receptors and actions in the nervous system. Physiol Rev 66:1121–1167
Mendelson SD, McEwen BS (1990) Adrenalectomy increases the density of 5-HT1A receptors in rat hippocampus. Neuroendocrinol Lett 12:353
Mendelson SD, McEwen BS (1992) Autoradiographic analyses of the effects of adrenalectomy and corticosterone on 5-HT1A and 5-HT1B receptors in the dorsal hippocampus and cortex of the rat. Neuroendocrinology 55:444–450
Meyer JS, Micco DJ, Stephenson BS, Krey LC, McEwen BS (1979) Subcutaneous implantation method for chronic glucocorticoid replacement therapy. Physiol Behav 22:867–870
Paxinos G, Watson C (1986) The rat brain in sterotaxic coordinates. Academic Press, New York
Poland R, Rubin R, Weischel M (1980) Circadian patterns of rat anterior pituitary and target gland hormones in serum: determination of the apparent the sample size by statistical power analysis. Psychoneuroendocrinology 5:209–224
Richter CP (1941) Sodium chloride and dextrose appetite of untreated and treated adrenalectomized rats. Endocrinology 29:115–125
Sapolsky RM, Krey LC, McEwen BS (1985) Prolonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging. J Neurosci 5:1222–1227
Sapolsky RM, Uno H, Rebert C, Finch C (1990) Hippocampal damage associated with prolonged glucocorticoid exposure in primates. J Neurosci 10:2897–2904
Sloviter RS, Valiquette G, Abrams GM, Ronk EC, Sollas AL, Paul LA, Neubort S (1989) Selective loss of hippocampal granule cells in the mature rat brain after adrenalectomy. Science 243:535–538
Sprouse JS, Aghajanian GK (1987) Electrophysiological reponses of serotonergic dorsal raphe neurons to 5-HT1A and 5-HT1B agonists. Synapse 1:3–9
Sze PY, Neckers L, Towle AC (1976) Glucocorticoids as a regulatory factor for brain tryptophan hydroxylase. J Neurochem 26:169–173
Uno H, Tarara R, Else JG, Suleman MA, Sapolsky RM (1989) Hippocampal damage associated with prolonged and fatal stress in primates. J Neurosci 9:1705–1711
Van de Kar LD (1991) Neuroendocrine pharmacology of serotonergic (5-HT) neurons. Annu Rev Pharmacol Toxicol 31:289–321
Van Loon GR, Shum A, Sole MJ (1981) Decreased brain serotonin turnover after short-term (two hour) adrenalectomy in rats: a comparison of four turnover methods. Endocrinology 108:1392–1401
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tejani-Butt, S.M., Labow, D.M. Time course of the effects of adrenalectomy and corticosterone replacement on 5-HT1A receptors and 5-HT uptake sites in the hippocampus and dorsal raphe nucleus of the rat brain: an autoradiographic analysis. Psychopharmacology 113, 481–486 (1994). https://doi.org/10.1007/BF02245227
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02245227