Corticosteroids regulate brain hippocampal 5-HT1A receptor mRNA expression.
Using in situ hybridization techniques, the expression of 5-HT1A receptor mRNA was measured within the hippocampal formation after bilateral adrenalectomy (ADX). After 24 hr ADX, 5-HT1A receptor mRNA expression was significantly increased in all hippocampal subfields in ADX animals relative to sham-operated controls (SHAM). The magnitude of the increase was most pronounced within CA2 (127%) and CA3/4 (94%)-subfields of dorsal hippocampus, intermediate in the dentate gyrus (73%), and least within CA1 (60%). Administration of exogenous corticosterone (CORT) at the time of ADX maintained the level of 5-HT1A receptor mRNA expression within the range of SHAM animals. In vitro receptor autoradiographic analysis of 5-HT1A receptors in adjacent sections from the same animals indicated a simultaneous increase in 5-HT1A binding throughout the hippocampus in response to ADX. 5-HT1A binding increased to a similar extent (approximately 30%) in CA subfields and dentate gyrus but remained within SHAM levels in CORT-replaced animals. 5-HT1A receptor mRNA levels were also increased in hippocampal subregions of 1 week ADX animals relative to SHAM animals. Within both CA1 and CA2 subfields, the increments were approximately double those observed after 1 d ADX. 5-HT1A receptor binding was increased in every hippocampal subfield to a similar extent as that observed after 1 d ADX. Increases in both 5-HT1A receptor mRNA expression and 5-HT1A receptor binding were preventable by administration of exogenous CORT at the time of ADX. Hippocampal 5-HT1C receptor mRNA and D1 receptor mRNA expression were not significantly altered by either acute or chronic ADX treatment. These data indicate that adrenal steroids may selectively regulate hippocampal 5-HT1A receptors at the level of 5-HT1A receptor mRNA expression.
Chalmers
D T
DT
Mental Health Research Institute, University of Michigan, Ann Arbor 48109.
Kwak
S P
SP
Mansour
A
A
Akil
H
H
Watson
S J
SJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000311:Adrenal Glands / Q000502:physiology*; D000315:Adrenalectomy; D000704:Analysis of Variance; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003345:Corticosterone / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D017403:In Situ Hybridization; D008297:Male; D011712:Pyramidal Tracts / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000235:genetics* / Q000378:metabolism*; D012016:Reference Values; D014158:Transcription, Genetic; D014316:Tritium
D012333:RNA, Messenger; D011985:Receptors, Serotonin; D014316:Tritium; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003345:Corticosterone