5-HT1A receptor agonist reverses adrenalectomy-induced loss of granule neuronal morphology in the rat dentate gyrus.

Adrenal steroids are important for maintaining neuronal maturation in the adult rats. Two weeks after bilateral adrenalectomy (ADX), hippocampal MAP-2 (microtubule associated protein-2) and calbindin immunoreactivity (IR) decreased in the molecular layer of the superior blade of the dentate gyrus. The molecular and granular cell layer at the lateral tip of the superior blade decreased in width by 32% and 50%, respectively. The granule neurons showed reduced staining with Nissl and an anti-calbindin antibody. These changes suggested a loss of the mature neuronal morphology. In this same localized regions, two glial proteins, glial fibrillary acidic protein (GFAP) and S-100 beta showed dramatically reduced immunoreactivity. These effects induced by ADX were reduced within 72 hrs by ipsapirone (1 mg/kg), a 5HT1A receptor agonist. Loss of adult neuronal morphology by ADX, and reversal by the 5HT1A agonist, may be evidence of the trophic importance of the 5HT1A receptor in granule neurons of hippocampus.