PMID- 16949621 OWN - NLM STAT- MEDLINE DCOM- 20070112 LR - 20211203 IS - 0028-3908 (Print) IS - 0028-3908 (Linking) VI - 51 IP - 5 DP - 2006 Oct TI - Binge administration of 3,4-methylenedioxymethamphetamine ("ecstasy") impairs the survival of neural precursors in adult rat dentate gyrus. PG - 967-73 AB - 3,4-Methylenedioxymethamphetamine (MDMA) is a potent stimulant and hallucinogenic drug whose ability to regulate neurogenesis in the adult has not been previously investigated. We used 5'-bromo-2-deoxyuridine (BrdU) and Ki-67 as mitotic markers, and doublecortin (DCX) as a marker of immature neurons, to study proliferation, survival and maturation of adult-generated cells in the dentate gyrus (DG) of the hippocampus following binge administration of MDMA (8 injections of 5 mg/kg at 6 h intervals). The results showed that MDMA treatment did not affect cytogenesis in the DG, but significantly decreased the survival rate of cells incorporated after 2 weeks to the granular layer of the DG by ca. 50%, and of those remaining in the subgranular layer by ca. 30%. Two weeks after exposure to MDMA the length of dendritic arbors and the number of dendritic branches of immature DCX+ neurons were nearly identical to those of control rats, as was the level of colocalization of BrdU with DCX. These results demonstrate that binge MDMA administration does not affect the proliferation rates of progenitor cells in the DG, but has deleterious effects on adult neurogenesis by impairing the short-term survival of vulnerable neural precursors. FAU - Hernandez-Rabaza, V AU - Hernandez-Rabaza V AD - Laboratory of Biopsychology and Comparative Neuroscience, Instituto Cavanilles, Universidad de Valencia, Poligono de la Coma s/n, Paterna, 46980 Valencia, Spain. FAU - Dominguez-Escriba, L AU - Dominguez-Escriba L FAU - Barcia, J A AU - Barcia JA FAU - Rosel, J F AU - Rosel JF FAU - Romero, F J AU - Romero FJ FAU - Garcia-Verdugo, J M AU - Garcia-Verdugo JM FAU - Canales, J J AU - Canales JJ LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060901 PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Dcx protein, rat) RN - 0 (Doublecortin Domain Proteins) RN - 0 (Doublecortin Protein) RN - 0 (Hallucinogens) RN - 0 (Ki-67 Antigen) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Neuropeptides) RN - G34N38R2N1 (Bromodeoxyuridine) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Analysis of Variance MH - Animals MH - Behavior, Animal/drug effects MH - Bromodeoxyuridine/metabolism MH - Cell Differentiation/drug effects/physiology MH - Cell Survival/drug effects MH - Dentate Gyrus/drug effects/*pathology MH - Doublecortin Domain Proteins MH - Doublecortin Protein MH - Hallucinogens/*administration & dosage MH - Immunohistochemistry/methods MH - Ki-67 Antigen/metabolism MH - Male MH - Microtubule-Associated Proteins/metabolism MH - N-Methyl-3,4-methylenedioxyamphetamine/*administration & dosage MH - Neurons/*drug effects MH - Neuropeptides/metabolism MH - Rats MH - Rats, Wistar MH - Stem Cells/*drug effects EDAT- 2006/09/05 09:00 MHDA- 2007/01/16 09:00 CRDT- 2006/09/05 09:00 PHST- 2006/04/26 00:00 [received] PHST- 2006/06/06 00:00 [revised] PHST- 2006/06/12 00:00 [accepted] PHST- 2006/09/05 09:00 [pubmed] PHST- 2007/01/16 09:00 [medline] PHST- 2006/09/05 09:00 [entrez] AID - S0028-3908(06)00190-0 [pii] AID - 10.1016/j.neuropharm.2006.06.019 [doi] PST - ppublish SO - Neuropharmacology. 2006 Oct;51(5):967-73. doi: 10.1016/j.neuropharm.2006.06.019. Epub 2006 Sep 1.