Corticosterone strongly increases the affinity of dorsal raphe 5-HT1A receptors.
The effects of corticosterone (10 mg/kg, s.c., 6 h) on dorsal raphe 5-HT1A autoreceptors have been studied in adrenalectomized rats with or without porcine galanin modulation. Adrenalectomy diminishes 5-HT1A autoreceptors affinity. Corticosterone increases 5-HT1A autoreceptor agonist affinity (+90%, p<0.001) in adrenalectomized rats. Galanin (10 nM) increases dorsal raphe 5-HT1A autoreceptor density (+65%, p<0.05) and its Kd value (+248%, p<0.05) only in adrenalectomized rats treated with corticosterone. Dorsal raphe glucocorticoid receptors activation by corticosterone may therefore lead to an increased signalling of 5-HT1A autoreceptors that may become counteracted by galanin receptor activation. Glucocorticoids, by enhancing dorsal raphe 5-HT1A autoreceptor function, may therefore cause reduced 5-HT neuronal activity and thus lead to a depressive state.
Bellido
Inmaculada
I
Department of Pharmacology and Clinical Therapeutics, School of Medicine, University of Malaga, MA-29071, Málaga, Spain. ibellido@uma.es
Hansson
Anita C
AC
Gómez-Luque
Aurelio J
AJ
Andbjer
Beth
B
Agnati
Luigi F
LF
Fuxe
Kjell
K
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology*; D003866:Depressive Disorder / Q000378:metabolism*; D019004:Galanin / Q000494:pharmacology; D008297:Male; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D019004:Galanin; D003345:Corticosterone