Central 5,7-Dihydroxytryptamine Lesions Decrease Hippocampal Glucocorticoid and Mineralocorticoid Receptor Messenger Ribonucleic Acid Expression

Corticosteroids exert effects on the hippocampus by binding to intracellular glucocorticoid and/or mineralocorticoid receptors, but the relative importance of each receptor type in mediating corticosteroid effects is poorly understood. There is an extensive serotoninergic (5-HT) innervation of the hippocampus which interacts with corticosteroid-sensitive cells. We have investigated the effect of intracerebroventricular 5,7-dihydroxytryptamine lesions of 5-HT neurons on glucocorticoid and mineralocorticoid receptor messenger ribonucleic acid (mRNA) expression in the rat hippocampus using in situ hybridization histochemistry. In controls, glucocorticoid receptor mRNA was highly expressed in dentate gyrus granule cell neurons, and in pyramidal cells of CA1 and CA2, but levels in CAS and CA4 were significantly lower. 5,7-dihydroxytryptamine-lesioned animals showed significantly less glucocorticoid receptor mRNA in the dentate gyrus (76% decrease), CA1 (42% decrease) and CA2 (52% decrease; all P<0.05 compared with controls). Mineralocorticoid receptor mRNA was expressed at a similar level in all hippocampal subregions in control rats. 5,7-dihydroxytryptamine lesioning led to a significant decrease in mineralocorticoid receptor mRNA expression in CA3 (56% fall) and CA4 (45% fall; both P<0.05), but not in the other subregions. Thus the 5-HT innervation regulates hippocampal corticosteroid receptor mRNA expression.