A single neonatal dose of methamphetamine suppresses dentate granule cell proliferation in adult gerbils which is restored to control values by acutedoses of haloperidol

A single non-invasive dose of methamphetamine (50mg/kg; i.p.) was administe red to neonatal male gerbils (Meriones unguiculatus) aged 14 days. The firs t objective of the present study was to examine whether this early drug cha llenge, which has been shown to induce suppressive postnatal maturation of prefrontal dopamine (DA) innervation (Dawirs et al., 1994), interferes with adult granule cell proliferation in the dentate gyrus. Proliferation of gr anule cells was identified by in-vivo labeling with 5-bromo-2'-desoxyuridin e (BrdU). BrdU-labeled granule cell nuclei were identified in consecutive h orizontal sections along the mid-septotemporal axis of the hippocampus and light-microscopically quantified 7 days after BrdU-labeling. It was found t hat a single neonatal dose of methamphetamine was a stimulus strong enough to significantly attenuate adult granule cell proliferation. This effect wa s clearly lateralized with significant suppression of mitotic activity beco ming apparent solely in the left dentate gyrus (-34%). The second objective of the present study was to examine whether acute doses of haloperidol, wh ich have been found to stimulate granule cell proliferation in healthy adul t animals (Dawirs et al., 1988), might restore mitotic activity to control values. For that purpose, at the age of postnatal day 90 adult animals whic h had been challenged with methamphetamine as juveniles received 4 doses of haloperidol (5mg/kg; i.p.). Proliferation of granule cells was identified by BrdU-labeling. It was found that this neuroleptic treatment acutely rest ored granule cell proliferation rates to control values. The present result s are discussed with regard to (1) factors, regulating mitotic activity in the hippocampus and (2) probable clues they may provide for understanding t he neurobiological basis of psychotic behavior.