Binge administration of 3,4-methylenedioxymethamphetamine ("ecstasy") impairs the survival of neural precursors in adult rat dentate gyrus.
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.
Hernández-Rabaza
V
V
Laboratory of Biopsychology and Comparative Neuroscience, Instituto Cavanilles, Universidad de Valencia, Poligono de la Coma s/n, Paterna, 46980 Valencia, Spain.
Domínguez-Escribà
L
L
Barcia
J A
JA
Rosel
J F
JF
Romero
F J
FJ
García-Verdugo
J M
JM
Canales
J J
JJ
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006213:Hallucinogens / Q000008:administration & dosage*; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage*; D009474:Neurons / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000187:drug effects*
C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006213:Hallucinogens; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D001973:Bromodeoxyuridine; D018817:N-Methyl-3,4-methylenedioxyamphetamine