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

The objective of the present study was to examine whether acute treatment w ith the recreational drug methamphetamine influences adult granule cell pro liferation in the dentate gyrus of the hippocampus. For that purpose, at th e age of postnatal day 90 adult male gerbils (Meriones unguiculatus) receiv ed a single dose of either methamphetamine (25 mg/kg; i.p.) or saline. Prol iferation of granule cells was identified by in-vivo labeling with 5-bromo- 2'-desoxyuridine (BrdU) which was applied either simultaneously with metham phetamine or 36h after administration of the drug. BrdU-labeled granule cel l nuclei were identified in consecutive horizontal slices along the mid-sep totemporal axis of the hippocampus and light-microscopically quantified 7 d ays after the BrdU-labeling. It was found that in both saline- and methamph etamine-treated animals there was a highly significant spatial septotempora l gradient in granule cell proliferation with numbers of BrdU-labeled cells gradually declining from the septal towards the temporal pole. The acute t reatment with methamphetamine suppressed granule cell proliferation by abou t 28% and the septotemporal gradient of mitotic activity became significant ly attenuated. It was further found that 36h after the drug challenge granu le 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 unders tanding the biological correlates of psychotic disorders and evolution of f uture concepts in neuropharmacological intervention.