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Neonatal 3,4-methylenedioxymethamphetamine (ecstasy) alters dopamine and serotonin neurochemistry and increases brain-derived neurotrophic factor in the forebrain and brainstem of the rat.
Brain Res Dev Brain Res. 2003 Dec 30; 147(1-2):177-82.BR

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+Show Affiliations

Department of Neurological Sciences, Rush University, Rush-Presbyterian-St. Luke's Medical Center, 1735 W. Harrison Street, Suite 265, Chicago, IL 60612, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14741762

Citation

Koprich, James B., et al. "Neonatal 3,4-methylenedioxymethamphetamine (ecstasy) Alters Dopamine and Serotonin Neurochemistry and Increases Brain-derived Neurotrophic Factor in the Forebrain and Brainstem of the Rat." Brain Research. Developmental Brain Research, vol. 147, no. 1-2, 2003, pp. 177-82.
Koprich JB, Campbell NG, Lipton JW. Neonatal 3,4-methylenedioxymethamphetamine (ecstasy) alters dopamine and serotonin neurochemistry and increases brain-derived neurotrophic factor in the forebrain and brainstem of the rat. Brain Res Dev Brain Res. 2003;147(1-2):177-82.
Koprich, J. B., Campbell, N. G., & Lipton, J. W. (2003). Neonatal 3,4-methylenedioxymethamphetamine (ecstasy) alters dopamine and serotonin neurochemistry and increases brain-derived neurotrophic factor in the forebrain and brainstem of the rat. Brain Research. Developmental Brain Research, 147(1-2), 177-82.
Koprich JB, Campbell NG, Lipton JW. Neonatal 3,4-methylenedioxymethamphetamine (ecstasy) Alters Dopamine and Serotonin Neurochemistry and Increases Brain-derived Neurotrophic Factor in the Forebrain and Brainstem of the Rat. Brain Res Dev Brain Res. 2003 Dec 30;147(1-2):177-82. PubMed PMID: 14741762.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neonatal 3,4-methylenedioxymethamphetamine (ecstasy) alters dopamine and serotonin neurochemistry and increases brain-derived neurotrophic factor in the forebrain and brainstem of the rat. AU - Koprich,James B, AU - Campbell,Nicholas G, AU - Lipton,Jack W, PY - 2004/1/27/pubmed PY - 2004/5/5/medline PY - 2004/1/27/entrez SP - 177 EP - 82 JF - Brain research. Developmental brain research JO - Brain Res. Dev. Brain Res. VL - 147 IS - 1-2 N2 - 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. SN - 0165-3806 UR - https://www.unboundmedicine.com/medline/citation/14741762/Neonatal_34_methylenedioxymethamphetamine__ecstasy__alters_dopamine_and_serotonin_neurochemistry_and_increases_brain_derived_neurotrophic_factor_in_the_forebrain_and_brainstem_of_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0165380603002190 DB - PRIME DP - Unbound Medicine ER -