Abstract
The effect of ACTH and/or adrenalectomy on serotonin (5-HT)2 receptor binding sites was evaluated in the neocortex of rat forebrain. One day after the adrenalectomy or sham operation, ACTH (50 µg/day) was injected subcutaneously into adult male SD rats for 10 consecutive days. Saturation analysis showed that subchronic ACTH treatment significantly increased the Bmax values for3H-ketanserin binding without any change in the Kd values. Moreover, this ACTH-induced increase in the Bmax values was prevented by adrenalectomy. The concentrations of 5-HT and 5-hydroxyindole acetic acid (5-HIAA) measured by HPLC-ECD were not altered by these manipulations. Ten-day administration of corticosterone (20 and 50 mg/kg) also increased 5-HT2 receptor density in the neocortex of rat forebrain. 5-HT2 (and 5-HT1C) receptor agonist, (±)DOI-induced wet-dog shakes in ACTH and/or adrenalectomy-treated rats were also examined. Ten-day administration of ACTH enhanced (±)DOI-induced wet-dog shakes and this increase was prevented by adrenalectomy. These results indicate that subchronic adrenocorticotropinadrenal axis activation of rats increases both the number of 5-HT2 receptors in neocortex of forebrain and the wet-dog shake responses induced by (±)DOI.
Similar content being viewed by others
References
Arango V, Ernsberger P, Marzuk PM, Chen J-S, Tierney H, Stanley M, Reis DJ, Mann JJ (1990) Autoradiographic demonstration of increased serotonin 5-HT2 and β-adrenergic receptor binding sites in the brain of suicide victims. Arch Gen Psychiatry 47:1038–1047
Arnt J, Hyttel J (1989) Facilitation of 8-OHDPAT-induced forepaw treading of rats by the 5-HT2 agonist DOI. Eur J Pharmacol 161:45–51
Arora RC, Meltzer HY (1989a) Increased serotonin-2(5-HT2) receptor binding as measured by3H-lysergic acid diethylamide (3H-LSD) in the blood platelets of depressed patients. Life Sci 44:725–734
Arora RC, Meltzer HY (1989b) Serotonergic measures in the brain of suicide victims: 5-HT2 binding sites in the frontal cortex of suicide victims and control subjects. Am J Psychiatry 146:730–736
Bedard P, Pycock CJ (1977) “Wet-dog” shake behaviour in the rat: a possible quantitative model of central 5-hydroxytryptamine activity. Neuropharmacology 16:663–670
Biegon A, Weizman A, Karp L, Ram A, Tiano S, Wolff M (1987) Serotonin 5-HT2 receptor binding on blood platelets — a peripheral marker for depression? Life Sci 41:2485–2492
Blackshear MA, Sanders-Bush E (1980) Serotonin receptor sensitivity after acute and chronic treatment with mianserin. J Pharmacol Exp Ther 221:303–308
Blackshear MA, Steranka LR, Sanders-Bush E (1981) Multiple serotonin receptors: regional distribution and effect of raphe lesions. Eur J Pharmacol 76:325–334
Carroll BJ, Curtis GC, Mendels J (1976) Neuroendocrine regulation in depression. I: Limbic system-adrenocortical dysfunction. Arch Gen Psychiatry 33:1039–1044
Cheetham SC, Crompton MR, Katona CLE, Horton RW (1988) Brain 5-HT2 receptor binding sites in depressed suicide victims. Brain Res 443:272–280
Clements-Jewery S, Robson PA (1982) Intact 5-HT neuroterminals are not required for 5-HT2 receptor down-regulation by amitriptyline. Neuropharmacology 21:725–727
Cohen SI (1980) Cushing's syndrome: a psychiatric study of 29 patients. Br J Psychiatry 136:120–124
Crow TJ, Cross AJ, Cooper SJ, Deakin JFW, Ferrier IN, Johnson JA, Joseph MH, Owen F, Poulter M, Lofthouse R, Corsellis JAN, Chambers DR, Blessed G, Perry EK, Perry RH, Tomlinson BE (1984) Neurotransmitter receptors and monoamine metabolites in the brains of patients with Alzheimer-type dementia and depression, and suicides. Neuropharmacology 23:1561–1569
Davies AO, Lefkowitz RJ (1980) Corticosterone-induced differential regulation of β-adrenergic receptors in circulating human polymorphonuclear leukocytes and mononuclear leukocytes. J Clin Endocrinol Metab 51:599–605
Dumbrille-Ross A, Tang SW, Coscina DV (1982) Lack of effect of raphe lesions on serotonin S2 receptor changes by amitriptyline and desmethylimipramine. Psychiatry Res 7:145–151
Eison AS, Yokka FD, Gianutsos G (1988) Noradrenergic denervation alters serotonin 2-mediated behavior but not serotonin 2 receptor number in rats: modulatory role of beta adrenergic receptors. J Pharmacol Exp Ther 246:571–577
Foster SJ, Harden TK (1980) Dexamethasone increases β-adrenoreceptor density in human astrocytoma cells. Biochem Pharmacol 29:2151–2153
Fraser CM, Venter JC (1980) The synthesis of β-adrenergic receptors in cultured human lung cells: induction by glucocorticoids. Biochem Biophys Res Commun 94:390–397
Gold PW, Goodwin FK, Chrousos GP (1988): Clinical and biochemical manifestations of depression: relation to the neurobiology of stress II. N Engl J Med 319:413–420
Hall H, Ross SB, Sällemark M (1984) Effect of destruction of central noradrenergic and serotonergic nerve terminals by systemic neurotoxins on the long term effects of antidepressants on β-adrenoceptors and 5-HT2 binding sites in the rat cerebral cortex. J Neural Transm 59:9–23
Handley SL, Singh L (1986) The modulation of head-twitch behaviour by drugs acting on beta-adrenoreceptors: evidence for the involvement of both beta1- and beta2-adrenoreceptors. Psychopharmacology 88:320–324
Haskett RF (1985) Diagnostic categorization of psychiatric disturbance in Cushing's syndrome. Am J Psychiatry 142:911–916
Heaton JCP, Njung'e K, Handley SL (1988) Behavioural profile of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a selective 5-HT2 agonist. Br J Pharmacol 94:388P
Kelly WF, Checkley SA, Bender DA (1980) Cushing's syndrome, tryptophan and depression. Br J Psychiatry 136:125–132
Kendall DA, Duman R, Slopis J, Enna SJ (1982) Influence of adrenocorticotropine hormone and yohimbine on antidepressant-induced declines in rat brain neurotransmitter receptor binding and function. J Pharmacol Exp Ther 222:566–571
Leysen JE, Niemegeers CJE, Van Nueten JM, Laduron PM (1982) [3H]ketanserin (R 41 468), a selective3H-ligand for serotonin2 receptor binding sites. Binding properties, brain distribution and functional role. Mol Pharmacol 21:301–314
Leysen JE, Van Gompel P, Verwimp M, Niemegeers CJE (1983) Role and localization of serotonin 2 (S2)-receptor-binding sites: Effect of neuronal lesions. In: Mandel P, DeFeudis FV (eds) CNS receptors-from molecular pharmacology to behavior. Raven Press, New York, pp 373–383
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
McBride PA, Brown RP, Demeo M, Kelip J, Stanley M, Mann JJ (1987) Platelet 5HT2 receptors: Depression and suicide. 140th Annual Meeting of the American Psychiatric Association
McKeith IG, Marshall EF, Ferrier IN, Armstrong MM, Kennedy WN, Perry RH, Perry EK, Eccleston D (1987) 5-HT receptor binding in post-mortem brain from patients with affective disorder. J Affect Disord 13:67–74
Mann JJ, Stanley M, McBride PA, McEwen BS (1986) Increased serotonin 2 and β-adrenergic receptor binding in the frontal cortices of suicide victims. Arch Gen Psychiatry 43:954–959
Martire M, Pistritto G, Preziosi P (1989) Different regulation of serotonin receptors following adrneal hormone imbalance in the rat hippocampus and hypothalamus. J Neural Transm 78:109–120
Mikuni M, Kusumi I, Kagaya A, Kuroda Y, Mori H, Takahashi K (1991) Increased 5-HT-2 receptor function as measured by serotonin-stimulated phosphoinositide hydrolysis in platelets of depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 15:49–61
Mikuni M, Kagaya A, Takahashi K, Meltzer HY (1992) Serotonin but not norepinephrine-induced calcium mobilization of platelets is enhanced in affective disorders. Psychopharmacology 106:311–314
Nemeroff CB, Widerlöv E, Bissette G (1984) Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 226:1342–1344
Nishikawa T, Mataga N, Takashima M, Toru M (1983) Behavioral sensitization and relative hyperresponsiveness of striatal and limbic dopaminergic neurons after repeated methamphetamine treatment. Eur J Pharmacol 88:195–203
Owen F, Chambers DR, Cooper SJ, Crow TJ, Johnson JA, Lofthouse R, Poulter M (1986) Serotonergic mechanisms in brains of suicide victims. Brain Research 362:185–188
Pandey GN, Pandey SC, Janicak PG, Marks RC, Davis JM (1990) Platelet serotonin-2 receptor binding sites in depression and suicide. Biol Psychiatry 28:215–222
Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic Press, Sydney
Peroutka SJ, Snyder SH (1980a) Long-term antidepressant treatment decreases spiroperidol-labeled serotonin receptor binding. Science 210:88–90
Peroutka SJ, Snyder SH (1980b) Regulation of serotonin2 (5-HT2) receptors labeled with3H spiroperidol by chronic treatment with the antidepressant amitriptyline. J Pharmacol Exp Ther 215:582–587
Pranzatelli MR (1988) Effect of antiepileptic and antimyoclonic drugs on serotonin receptors in vitro. Epilepsia 29:412–419
Pranzatelli MR (1990a) Evidence for involvement of 5-HT2 and 5-HT1c receptors in the behavioral effects of the 5-HT agonist 1-(2,5-dimethoxy-4-iodophenyl aminopropane)-2(DOI). Neurosci Lett 115:74–80
Pranzatelli MR (1990b) In vivo and in vitro effects of adrenocorticotropic hormone on serotonin receptors in neonatal rat brain. Dev Pharmacol Ther 12:49–56
Rodan SB, Rodan GA (1986) Dexamethasone effects on β-adrener gic receptors and adenylate cyclase regulatory proteins Gs and Gi in ROS 17/2.8 cells. Endocrinology 118:2510–2518
Scatchard G (1949) The attraction of proteins for small ions and molecules. Ann NY Acad Sci 51:660–672
Spillane JD (1951) Nervous and mental disorders in Cushing's syndrome. Brain 74:72–94
Stanley M, Mann JJ (1983) Increased serotonin-2 binding sites in frontal cortex of suicide victims. Lancet i:214–216
Stockmeier CA, Kellar KJ (1986) In vivo regulation of serotonin-2 receptor in rat brain. Life Sci 38:117–127
Yates M, Leake A, Candy JM, Fairbairn AF, McKeith IG, Ferrier IN (1990) 5HT2 receptor changes in major depression. Biol Psychiatry 27:489–496
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kuroda, Y., Mikuni, M., Ogawa, T. et al. Effect of ACTH, adrenalectomy and the combination treatment on the density of 5-HT2 receptor binding sites in neocortex of rat forebrain and 5-HT2 receptor-mediated wet-dog shake behaviors. Psychopharmacology 108, 27–32 (1992). https://doi.org/10.1007/BF02245281
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02245281