PMID: 12763094May 24, 2003Paper

Chronic AMPA receptor potentiator (LY451646) treatment increases cell proliferation in adult rat hippocampus

Neuropharmacology
F BaiD L Nelson

Abstract

Stress-induced neuronal atrophy and death in the hippocampus may play an important role in the etiology of clinical depression. Conventional antidepressants can stimulate hippocampal neurogenesis after chronic administration. AMPA receptor potentiators (ARPs) such as LY392098 and LY451616 are active in both the forced swim test and the tail suspension test, two behavioral despair procedures widely used to predict antidepressant efficacy. Unlike traditional antidepressants, this group of compounds does not affect extracellular concentrations of biogenic amines. In this study, we investigated the effect of LY451646 on progenitor cell proliferation in adult rat hippocampus. Male Sprague-Dawley rats (n = 4-5 per group) received either single or chronic (21 days) doses of LY451646 (0.025-0.5 mg/kg). Bromodeoxyuridine (BrdU) injections and immunohistochemistry were performed 30 min and 24 h after the last drug injection, respectively. Results show that chronic LY451646 treatment increased progenitor cell proliferation (approximately 45%) in the dentate gyrus in a dose-dependent manner. This upregulation of BrdU labeling appeared as an increase in the number of cells arranged in clusters. Similarly, a significant increase in the numbe...Continue Reading

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