Corticosteroids regulate brain hippocampal 5-HT1A receptor mRNA expression

Abstract

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.

Regulation of Hippocampal 5-HT1A Receptor Gene Expression by Dexamethasone

“…The present studies were designed to investigate the effect of dexamethasone administration on hip pocampal5-HT1A receptor modulation. In agreement with previous experiments (Mendelson and McEwen 1992;Chalmers et al 1993), the present data indicate that hippocampal 5-HT1A receptor mRNA expression and 5-HT1A binding are sensitive to circulating corti costeroid levels. One week ADX treatment induced large increases in 5-HT1A mRNA abundance across hippocampal subfields.…”

Hyperforin-Containing Extracts of St John's Wort Fail to Alter Gene Transcription in Brain Areas Involved in HPA Axis Control in a Long-Term Treatment Regimen in Rats

“…On the other hand, corticosteroids have been shown to alter several elements of serotonergic neurotransmission. The removal of circulating corticosteroids by adrenalectomy resulted in anatomically specific decreases in the indices of 5-HT metabolism (Chalmers et al, 1993;De Kloet et al, 1982;Zhong and Ciaranello, 1995). It is therefore likely that the increased ACTH and corticosterone levels observed in the present study after 2 weeks of fluoxetine treatment do not result from changes in HPA activity, but rather reflect a direct effect on pituitary cells caused by increased levels of serotonin.…”

“…Autoradiographic studies first identified increased 5-HT 1A receptor binding in the rat hippocampus after adrenalectomy (Biegon et al, 1985). Subsequent investigations have confirmed the sensitivity of 5-HT 1A receptors to circulating corticosteroid levels (Chalmers et al, 1993(Chalmers et al, , 1994Zhong and Ciaranello, 1995). However, the fact that in the present study, plasma ACTH and corticosterone levels were found to be elevated after 2 weeks whereas hippocampal 5-HT 1A mRNA was upregulated after 8 weeks indicates that differential or delayed regulatory mechanisms are operating to adjust limbic 5-HT 1A receptor number during fluoxetine treatment.…”

Serotonin and Hippocampal Neurogenesis

“…A considerable body of evidence suggests that 5HT may stimulate the production of neurons in the dentate gyrus. First, conditions that are associated with diminished granule cell genesis, such as malnutrition (Debassio et al 1996), aging (Kuhn et al 1996;Gould et al 1999), high corticosterone (Cameron and Gould 1994), stress , and NMDA receptor activation (Cameron et al 1995), also decrease the density of 5HT fibers or 5HT1A receptors, or inhibit the release of 5HT in the dentate gyrus (Blatt et al 1994;Chalmers et al 1993;McKittrick et al 1995;Nishimura et al 1995;Meijer and deKloet 1994;Watanabe et al 1993;Tao and Auerbach 1996;Whitton et al 1994;Nyakas et al 1997). Second, experimental manipulations that stimulate granule cell genesis, such as seizures (Parent et al 1997), adrenalectomy (Cameron and Gould 1994), and NMDA receptor antagonist treatment (Cameron et al 1995), also increase the density of 5HT1A receptors or the release of 5HT in the dentate gyrus (Hayakawa et al 1994;Burnet et al 1995;Whitton et al 1994;Kuroda et al 1994).…”