ADULT TREATMENT WITH HALOPERIDOL INCREASES DENTATE GRANULE CELL-PROLIFERATION IN THE GERBIL HIPPOCAMPUS

Male gerbils were bred and reared grouped under enriched seminatural e nvironmental conditions. The objective of the present study was to exa mine the influence of an acute treatment with the neuroleptic haloperi dol on adult granule cell neurogenesis in the hippocampus. For that pu rpose, at the age of postnatal day 90 adult animals received 4 challen ges of either haloperidol (5 mg/kg, i.p.) or saline. Proliferation of granule cells was identified by in-vivo labeling with 5-bromo-2'-desox yuridine (BrdU) which was applied 1 hour after the final dose of halop eridol. BrdU-labeled granule cell nuclei were identified in consecutiv e horizontal slices along the mid-septotemporal axis of the hippocampu s and light-microscopically quantified 7 days after the BrdU-labeling. It was found that in both saline-and haloperidol-treated animals ther e was a highly significant spatial septotemporal gradient in granular cell proliferation with numbers of BrdU-labeled cells gradually declin ing from the septal towards the temporal pole. The acute treatment wit h haloperidol stimulated granule cell proliferation by about 75 % and the septotemporal gradient of mitotic activity became significantly en hanced. The present results are discussed with regard to known factors regulating cell proliferation in the hippocampus and other cell syste ms.