Corticosteroid effects on serotonin responses in granule cells of the rat dentate gyrus.
Granule cells in the rat dentate gyrus contain mineralocorticoid and glucocorticoid receptors to which the adrenal hormone corticosterone binds with differential affinity. These cells also express various receptor-subtypes for serotonin (5-HT), including the 5-HT1A receptor which mediates a membrane hyperpolarization accompanied by a decrease in membrane resistance. Earlier studies have shown that removal of corticosterone by adrenalectomy, particularly in the dentate gyrus, results in enhanced expression of the 5-HT1A receptor mRNA and increased 5-HT1A receptor binding capacity. This was normalized by activation of mineralocorticoid receptors or concurrent activation of both receptor types. In the present, intracellular recording study in vitro, we examined if the altered levels of 5-HT1A receptor mRNA and protein are associated with changes in the response to 5-HT. We found that the hyperpolarization and resistance decrease induced in granule cells by a submaximal (10 microM) dose of 5-HT were unaltered 2-4 days after adrenalectomy, indicating a dissociation between corticosteroid actions on 5-HT1A receptor mRNA/protein levels and functional responses to 5-HT. Subsequent occupation of mineralocorticoid receptors in vitro significantly suppressed the 5-HT induced change in resistance, 1-4 h after steroid application. Compared to this, concurrent activation of glucocorticoid receptors led to large responses to 5-HT. This modulation by steroids was not observed with a higher dose of 5-HT (30 microM). The data suggest that with moderate amounts of 5-HT, corticosteroids affect the information flow through the dentate gyrus such that excitatory transmission is promoted with predominant mineralocorticoid receptor activation and attenuated with additional glucocorticoid receptor occupation.
Karten
Y J
YJ
Swammerdam Institute for Life Sciences, University of Amsterdam, 1090 GB Amsterdam, The Netherlands.
Stienstra
C M
CM
Joëls
M
M
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology; D017097:Electric Impedance; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D015735:Mifepristone / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D011985:Receptors, Serotonin / Q000032:analysis / Q000235:genetics; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*
D000305:Adrenal Cortex Hormones; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D015735:Mifepristone; D012701:Serotonin; D003345:Corticosterone