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

Abstract

A single non-invasive dose of methamphetamine (50 mg/kg; i.p.) was administered to neonatal male gerbils (Meriones unguiculatus) aged 14 days. The first objective of the present study was to examine whether this early drug challenge, 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 granule cells was identified by in-vivo labeling with 5-bromo-2'-desoxyuridine (BrdU). BrdU-labeled granule cell nuclei were identified in consecutive horizontal sections along the mid-septotemporal axis of the hippocampus and light-microscopically quantified 7 days after BrdU-labeling. It was found that a single neonatal dose of methamphetamine was a stimulus strong enough to significantly attenuate adult granule cell proliferation. This effect was clearly lateralized with significant suppression of mitotic activity becoming apparent solely in the left dentate gyrus (-34%). The second objective of the present study was to examine whether acute doses of haloperidol, which have been found to stimulate granule cell proliferation in healthy adult animals (Dawirs et al., 1988), might restore mitotic activity to control values. For that purpose, at the age of postnatal day 90 adult animals which had been challenged with methamphetamine as juveniles received 4 doses of haloperidol (5 mg/kg; i.p.). Proliferation of granule cells was identified by BrdU-labeling. It was found that this neuroleptic treatment acutely restored granule cell proliferation rates to control values. The present results are discussed with regard to (1) factors, regulating mitotic activity in the hippocampus and (2) probable clues they may provide for understanding the neurobiological basis of psychotic behavior.