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Neuropsychopharmacology. 2005 Feb;30(2):231-41.

Serotonin modulates the suppressive effects of corticosterone on proliferating progenitor cells in the dentate gyrus of the hippocampus in the adult rat.

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1
Department of Anatomy, Cambridge Centre for Brain Repair, University of Cambridge, UK.

Abstract

This series of experiments explores the interaction between corticosterone and serotonin (5-HT) in the regulation of cell proliferation in the dentate gyrus of the adult rat. Intracerebroventricular 5,7-DHT (5,7-dihydroxytryptamine) (either 200 or 300 microg) resulted in highly significant depletion of 5-HT as measured by high performance liquid chromatography in the frontal cortex but had no effect on the number of proliferating cells in the dentate gyrus by measuring 5-bromo-2'-deoxyuridine (BrdU) and Ki-67 cytochemistry. Treatment with PCPA (p-chlorophenylalanine: a tryptophan hydroxylase inhibitor: 300 mg/kg initially followed by 100 mg/kg/day) resulted in reduced proliferation as measured by Ki-67 after 3 days treatment, but not by BrdU uptake, and not after 14 days treatment by either method. In addition, injection of corticosterone (10-40 mg/kg/day) for 8 days significantly reduced proliferation in the dentate gyrus, as expected, measured by both BrdU uptake and Ki-67 immunostaining. Adrenalectomized (ADX) rats with a replacement subcutaneous pellet of corticosterone showed reduced proliferation when given additional corticosterone (10 mg/kg/day for 8 days), but this was prevented by 5-HT depletion (i.c.v. 5,7-DHT). Finally, a dose-response study showed that progressive doses of corticosterone (0-40 mg/kg/day) in ADX rats resulted in diminished suppression of proliferation in 5-HT-depleted compared with 5-HT-intact rats. These results strongly suggest that 5-HT regulates the sensitivity of proliferating cells in the dentate gyrus to corticosterone.

PMID:
15536491
PMCID:
PMC2651121
DOI:
10.1038/sj.npp.1300609
[Indexed for MEDLINE]
Free PMC Article
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