title: Neonatal 3,4-methylenedioxymethamphetamine (ecstasy) alters dopamine and serotonin neurochemistry and increases brain-derived neurotrophic factor in the forebrain and brainstem of the rat.
abstract: Growing concerns surround the risk of fetal exposure to 3,4-methylenedioxymethamphetamine (MDMA; ecstasy). Prior animal studies using neonatal rats administered MDMA from postnatal days (P) 11-20 (a period approximating third trimester brain development in humans) have demonstrated long-lasting decrements in serotonin (5-HT) and learning; however, no studies have examined the acute post-MDMA response of the brain at this early age. Specifically, it is of interest whether MDMA administration to neonatal rats produces the expected depletion of monoamines and whether the brain exhibits any ameliorative response to the pharmacologic insult. In the current study, this model was employed to determine whether forebrain and brainstem dopamine (DA) and 5-HT neurochemistry were altered 24 h after the last injection (P21), and whether brain-derived neurotrophic factor (BDNF) was upregulated in response to MDMA exposure. All forebrain structures examined (frontal cortex, hippocampus, and striatum) showed significant MDMA-induced reductions in 5-HT and its metabolite, 5-HIAA, and significant increases in the DA metabolite, HVA, as well as DA turnover (HVA/DA). In the brainstem, there were significant increases in 5-HIAA, HVA and DA turnover. BDNF was significantly increased (19-38%) in all forebrain structures and in the brainstem in MDMA-exposed neonates versus saline controls. These data suggest that MDMA exposure to the developing rat brain from P11-20 produces similar alterations in serotonin and dopamine neurochemistry to those observed from adult administrations. In addition, a compensatory increase in BDNF was observed and may be the brains ameliorative response to minimize MDMA effects. This is the first report demonstrating that MDMA exposure results in increased levels of BDNF and that such increases are correlated with changes in monoamine levels. Future research is needed to elucidate any deleterious effects MDMA-induced increases in trophic activity might have on the developing brain and to examine earlier gestational exposure periods in order to assess the risk throughout pregnancy.
authors.affiliation: Department of Neurological Sciences, Rush University, Rush-Presbyterian-St. Luke's Medical Center, 1735 W. Harrison Street, Suite 265, Chicago, IL 60612, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Koprich
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Campbell
authors.forename: Jack W
authors.initials: JW
authors.lastname: Lipton
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects*; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006213:Hallucinogens / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D006213:Hallucinogens; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine