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
- 68 Downloads
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.
Key wordsSerotonin-2 (5-HT2) binding site Ketanserin ACTH Corticosterone Adrenalectomy DOI Wet-dog shakes
Unable to display preview. Download preview PDF.
- Arnt J, Hyttel J (1989) Facilitation of 8-OHDPAT-induced forepaw treading of rats by the 5-HT2 agonist DOI. Eur J Pharmacol 161:45–51Google Scholar
- Blackshear MA, Sanders-Bush E (1980) Serotonin receptor sensitivity after acute and chronic treatment with mianserin. J Pharmacol Exp Ther 221:303–308Google Scholar
- 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 23:1561–1569CrossRefPubMedGoogle Scholar
- 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 59:9–23CrossRefPubMedGoogle Scholar
- 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 94:388PGoogle Scholar
- 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 373–383Google Scholar
- 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 AssociationGoogle Scholar
- Nemeroff CB, Widerlöv E, Bissette G (1984) Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 226:1342–1344Google Scholar
- Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic Press, SydneyGoogle Scholar
- Pranzatelli MR (1990b) In vivo and in vitro effects of adrenocorticotropic hormone on serotonin receptors in neonatal rat brain. Dev Pharmacol Ther 12:49–56Google Scholar
- Scatchard G (1949) The attraction of proteins for small ions and molecules. Ann NY Acad Sci 51:660–672Google Scholar