Developmental exposure to 3,4-methylenedioxymethamphetamine results in downregulation of neurogenesis in the adult mouse hippocampus.
3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a powerful releaser of 5-HT and chronic use of this drug can cause depletion of monoamines. Recently, concerns about the risk of adult brain damage due to fetal exposure to MDMA have been raised. We investigated whether developmental MDMA exposure affected adult neurogenesis in C57 black/6 mice. MDMA (1.25 or 20 mg/kg, p.o.) or vehicle was administered daily to the mother from prenatal 6th day to postnatal 21st day. When the offspring were 11 weeks old, they were injected with 5-bromo-2'-deoxyuridine (BrdU) (120 mg/kg, i.p.) once a day for 4 days. After 24 h or 28 days, the animals were killed to count the BrdU-positive cells in the dentate gyrus. At 24 h after the last BrdU injection, the number of BrdU-positive cells in the offspring developmentally exposed to MDMA was significantly lower than that of the control group. At 28 days post-BrdU labeling, BrdU-positive cells in the dentate gyrus of female offspring with developmental exposure to high dose MDMA were significantly fewer compared with the control group. In addition, most BrdU-positive cells were co-labeled with the mature neuronal marker, neuronal nuclei, while a few BrdU-labeled cells were merged with an astrocyte marker. Our results suggest that developmental exposure to MDMA can result in decreases in the proliferation and survival of mature newborn cells in the adult dentate gyrus.
Cho
K-O
KO
Department of Pharmacology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul, 137-701, Korea.
Rhee
G S
GS
Kwack
S J
SJ
Chung
S Y
SY
Kim
S Y
SY
D000818:Animals; D000963:Antimetabolites; D001253:Astrocytes / Q000187:drug effects; D001724:Birth Weight / Q000502:physiology; D001973:Bromodeoxyuridine; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D006213:Hallucinogens / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development*; D007150:Immunohistochemistry; D007774:Lactation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016019:Survival Analysis; D015430:Weight Gain / Q000502:physiology
D000963:Antimetabolites; D006213:Hallucinogens; D001973:Bromodeoxyuridine; D018817:N-Methyl-3,4-methylenedioxyamphetamine