Modulation of 5-HT receptor subtype-mediated behaviours by corticosterone.
Malfunction of the serotonergic system and dysregulation of the hypothalamo-pituitary-adrenocortical axis have been implicated in the pathophysiology of depression. Several studies provide evidence for reciprocal influences between glucocorticoids and 5-HT receptors. The effect of repeated treatment with a high dose of corticosterone (50 mg/kg s.c. twice daily for 4 days) on 5-HT receptor subtype-mediated behaviours was studied. It was found that in rats that were repeatedly treated with corticosterone the number of 2-chloro-6-(1-piperazinyl)pyrazine HCl (MK 212)-induced, 5-HT2C receptor-mediated penile erections were reduced, whereas both MK 212 and (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced 5-HT2A receptor-mediated head shakes were increased. The (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)-induced lower lip retraction mediated by presynaptic 5-HT1A receptors was unchanged, whereas the open field activity induced by 8-OH-DPAT was enhanced in corticosterone pretreated rats. These changes in 5-HT receptor subtype-mediated behaviours were not seen after a single injection with corticosterone given 24 h or 5 days before. The results suggest that 5-HT2A, 5-HT2C and postsynaptic 5-HT1A receptor-mediated behaviour can be modulated by repeated treatment with a high dose of corticosterone.
Berendsen
H H
HH
Department of Neuropharmacology, N.V. Organon, P.O.B. 20, 5340 BH Oss, Netherlands.
Kester
R C
RC
Peeters
B W
BW
Broekkamp
C L
CL
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000662:Amphetamines; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003345:Corticosterone / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D011719:Pyrazines; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000662:Amphetamines; D011719:Pyrazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D003345:Corticosterone