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.

Male gerbils were bred and reared grouped under enriched semi-natural environmental conditions. The objective of the present study was to examine the influence of an acute treatment with the neuroleptic haloperidol on adult granule cell neurogenesis in the hippocampus. For that purpose, at the age of postnatal day 90 adult animals received 4 challenges of either haloperidol (5 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 1 hour after the final dose of haloperidol. 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 haloperidol-treated animals there was a highly significant spatial septotemporal gradient in granular cell proliferation with numbers of BrdU-labeled cells gradually declining from the septal towards the temporal pole. The acute treatment with haloperidol stimulated granule cell proliferation by about 75% and the septotemporal gradient of mitotic activity became significantly enhanced. The present results are discussed with regard to known factors regulating cell proliferation in the hippocampus and other cell systems.

Adult neurogenesis is a key feature of the hippocampal dentate gyrus (DG). Neurogenesis is accompanied by synaptogenesis as new cells become integrated into the circuitry of the hippocampus. However, little is known to what extent the embedding of new neurons rewires the pre-existing network. Here we investigate synaptic rewiring in the DG of gerbils (Meriones unguiculatus) under different rates of adult cell proliferation caused by different rearing conditions as well as juvenile methamphetamine treatment. Surprisingly, we found that an increased cell proliferation reduced the amount of synaptic rewiring. To help explain this unexpected finding, we developed a novel model of dentate network formation incorporating neurogenesis and activity-dependent synapse formation and remodelling. In the model, we show that homeostasis of neuronal activity can account for the inverse relationship between cell proliferation and synaptic rewiring.

No abstract

Male gerbils (Meriones unguiculatus) were bred and reared either grouped under enriched environmental conditions or isolated under impoverished environmental conditions. The objective of the present study was to examine the influence of social environment on structural and functional ontogeny of the medial prefrontal cortex (mPFC). In this respect, we investigated the maturation of both prefrontal dopamine (DA) innervation and working memory. For that purpose, at the age of postnatal day 90, prefrontal DA fibers were stained immunocytochemically using an antibody against glutaraldehyde-conjugated DA and innervation density was determined by means of a computer controlled program for image analysis. In order to evaluate environmental effects on working memory, 90-day-old gerbils were tested for y-maze delayed alternation. It was found that, isolation produced a significant and severe restraint of the maturation of prefrontal DA innervation, leading to fiber densities which were 56% below those in group-reared gerbils. Isolation also induced a significant impairment of delayed alternation performance on the y-maze indicating that obvious deficits in working memory had developed under restricted rearing conditions. The present results are discussed with regard to activity-dependent postnatal maturation of the cortex and adaptive neuroplasticity.