Summary
The effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and some other 5-hydroxytryptamine1A (5-HT1A) receptor agonists (buspirone, ipsapirone and flesinoxan) on corticosterone secretion in rats were studied. The 5-HT1A receptors mediating the corticosterone secretion appear to be postsynaptic to the 5-HT neurons, since the response to 8-OH-DPAT was not decreased but potentiated by depletion of 5-HT with p-chlorophenylalanine pretreatment of the animals. Rapid attenuation of the response was developed after a single dose of a 5-HT1A receptor agonist. Thus, 1 mg/kg s.c. of 8-OH-DPAT attenuated the response of a challenge dose (0.1 mg/kg s.c.) of this compound within 4 h lasting between 7 and 14 d. The development of the subsensitivity was antagonized by pretreatment of the rats with the 5-HT1A receptor antagonist S-5-fluoro-8-hydroxy-2-(di-n-propylamino)tetralin ((−)-UH 301). This compound also antagonized the acute effect of 8-OH-DPAT in increasing serum corticosterone. The subsensitivity development was specific for the 5-HT1A receptor-mediated corticosterone secretion, since the increase in serum corticosterone produced by stimulation of other receptor systems, e.g. α2-adrenoreceptors (clonidine) or 5-HT2 receptors [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, (DOI)] was not affected.
Similar content being viewed by others
References
Beer M, Kennett GA, Curzon G (1990) A single dose of 8-OH-DPAT reduces raphe binding of [3H]8-OH-DPAT and increases the effect of raphe stimulation on 5-HT metabolism. Eur J Pharmacol 178:179–187
Björk L,Cornfield LJ, Nelson DL, Hillver S-E, Andén N-E, Lewander T, Hacksell U (1991) Pharmacology of the novel 5-hydroxytryptamine1A receptor antagonist (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin: Inhibition of (R)-8-hydroxy-2-(dipropylamino)tetraline-induced effects. J Pharmacol Exp Ther 258:58–65
Feldman S, Conforti N, Melamed E (1987) Paraventricular nucleus serotonin mediates neurally stimulated adrenocortical secretion. Brain Res Bull 18:165–168
Fuller RW (1981) Serotonergic stimulation of pituitary-adrenal function in rats. Neuroendocrinology 32:118–127
Gilbert F, Brazell C, Tricklebank MD, Stahl SM (1988) Activation of the 5-HT1A receptor subtype increases rat plasma ACTH concentrations. Eur J Pharmacol 142:431–437
Goodwin GM, DeSouza RJ, Green AR, Heal DJ (1987) The pharmacology of the behavioural and hypothermic responses of rats to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), Psychopharmacology 91:506–511
Haleem DJ, Kennett GA, Whitton PS, Curzon G (1989) 8-OH-DPAT increases corticosterone but not other 5-HT1A receptor-dependent responses more in females. Eur J Pharmacol 164:435–443
Hjorth S (1985) Hypothermia in the rat induced by the potent serotonergic agent 8-OH-DPAT. J Neural Transm 61:131–135
Hjorth S, Carlsson A, Lindberg P, Sanchez D, Wikström H, Arvidsson L-E, Hacksell U, Nilsoon JLG (1982) 8-Hydroxy-2-(di-n-pro-pylamino)tetralin, a potent and selective simplified ergot congener with central 5-HT-receptor stimulating activity. J Neural Transm 55:169–188
Hutson PH, Donohoe TP, Curzon G (1987) Hypothermia induced by the putative 5-HT1A agonists LY 165163 and 8-OH-DPAT is not prevented by 5-HT depletion. Eur J Pharmacol 145:221–228
Koenig JI, Gudelsky GA, Meltzer HY (1987) Stimulation of corticosterone and β-endorphin secretion in the rat by selective 5-HT receptor subtype activation. Eur J Pharmacol 137:1–8
Koenig JI, Meltzer HY, Gudelsky GA (1988) 5-Hydroxytryptamine1A receptor-mediated effects of bispirone, gepirone and ipsapirone. Pharmacol Biochem Behav 29:711–715
Larsson L-G, Renyi L, Ross SB, Svensson B, Ängeby-Möller K (1990) Different effects on the responses of functional pre- and postsynaptic 5-HT1A receptors by repeated treatment of rats with the 5-HT1A receptor agonist 8-OH-DPAT. Neuropharmacology 29:85–91
Lorens SA, Van de Kar LD (1987) Differential effects of serotonin (5-HT1A and 5-HT2) agonists and antagonists of renin and corticosterone secretion. Neuroendocrinology 45:305–310
Nash JF, Meltzer HY, Gudelsky GA (1989) Selective cross-tolerance to 5-HT1A and 5-HT2 receptor-mediated temperature and corticosterone responses. Pharmacol Biochem Behav 33:781–785
Przegaliński E, Budziszewska B, Warchol-Kania A, Blaszczyńska E (1989) Stimulation of corticosterone secretion by the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Pharmacol Biochem Behav 33:329–334
Rényi L, Ängeby-Möller K, Evenden J (1991) Single dose of 8-OH-DPAT attenuated rapidly and longlastingly the 5-HT1A receptor mediated hypothermic response in rats. Serotonin 1991. 5-Hydroxytryptamine — CNS receptors and brain function. International conference, 14th–17th July, Birmingham. Abstr p 91
Ross SB, Rényi L, Kelder D (1992) N-Methyl-D-aspartate receptor antagonists counteract the long lasting 5-HT1A receptor-induced attenuation of postsynaptic responses in the rat in vivo. NaunynSchmiedeberg's Arch Pharmacol 346:138–143
Schechter LE, Bolanos FJ, Gozlan H, Lanfumey L, Haj-Dahmane S, Laporte A-M, Fattacini C-M, Hamon M (1990) Alterations of central serotoninergic and dopaminergic neurotransmission in rats chronically treated with ipsapirone: Biochemical and electrophysiological studies. J Pharmacol Exp Ther 255:1335–1347
Swanson LW, Sawchenko PE, Rivier J, Vale WW (1983) Organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study. Neuroendocrinology 36:165–186
Tricklebank MD, Forler C, Fozard JR (1985) The involvement of subtypes of the 5-HT1 receptor of catecholaminergic systems in the behavioural response to 8-hydroxy-2-(di-n-propylamino)tetralin in the rat. Eur J Pharmacol 106:271–282
Wouters W, Tulp MTM, Bevan P (1988) Flesinoxan lowers blood pressure and heart rate via 5-HT1A receptors. Eur J Pharmacol 149:213–233
Author information
Authors and Affiliations
Additional information
Send offprint requests to S. B. Ross at the above address
Rights and permissions
About this article
Cite this article
Kelder, D., Ross, S.B. Long lasting attenuation of 8-OH-DPAT induced corticosterone secretion after a single injection of a 5-HT1A receptor agonist. Naunyn-Schmiedeberg's Arch Pharmacol 346, 121–126 (1992). https://doi.org/10.1007/BF00165292
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00165292