Adult treatment with methamphetamine transiently decreases dentate granule cell proliferation in the gerbil hippocampus

Abstract

The objective of the present study was to examine whether acute treatment with the recreational drug methamphetamine influences adult granule cell proliferation in the dentate gyrus of the hippocampus. For that purpose, at the age of postnatal day 90 adult male gerbils (Meriones unguiculatus) received a single dose of either methamphetamine (25 mg/kg; i.p.) or saline. Proliferation of granule cells was identified by in-vivo labeling with 5-bromo-2'-desoxyuridine (BrdU) which was applied either simultaneously with methamphetamine or 36 h after administration of the drug. BrdU-labeled granule cell nuclei were identified in consecutive horizontal slices along the mid-septotemporal axis of the hippocampus and light-microscopically quantified 7 days after the BrdU-labeling. It was found that in both saline- and methamphetamine-treated animals there was a highly significant spatial septotemporal gradient in granule cell proliferation with numbers of BrdU-labeled cells gradually declining from the septal towards the temporal pole. The acute treatment with methamphetamine suppressed granule cell proliferation by about 28% and the septotemporal gradient of mitotic activity became significantly attenuated. It was further found that 36 h after the drug challenge granule cell proliferation rates had been restored almost to the control values along the whole septotemporal axis of the hippocampus. The present results are discussed with regard to (1) pharmacological regulation of neurogenesis in the hippocampus and (2) probable clues they may provide for both understanding the biological correlates of psychotic disorders and evolution of future concepts in neuropharmacological intervention.