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Evidence for a role of energy dysregulation in the MDMA-induced depletion of brain 5-HT.
Brain Res. 2005 Sep 21; 1056(2):168-75.BR

Abstract

Although the exact mechanism involved in the long-term depletion of brain serotonin (5-HT) produced by substituted amphetamines is not completely known, evidence suggests that oxidative and/or bioenergetic stress may contribute to 3,4-methylenedioxymethamphetamine (MDMA)-induced 5-HT toxicity. In the present study, the effect of supplementing energy substrates was examined on the long-term depletion of striatal 5-HT and dopamine produced by the local perfusion of MDMA (100 microM) and malonate (100 mM) and the depletion of striatal and hippocampal 5-HT concentrations produced by the systemic administration of MDMA (10 mg/kg i.p. x4). The effect of systemic administration of MDMA on ATP levels in the striatum and hippocampus also was examined. Reverse dialysis of MDMA and malonate directly into the striatum resulted in a 55-70% reduction in striatal concentrations of 5-HT and dopamine, and these reductions were significantly attenuated when MDMA and malonate were co-perfused with nicotinamide (1 mM). Perfusion of nicotinamide or ubiquinone (100 microM) also attenuated the depletion of 5-HT in the striatum and hippocampus produced by the systemic administration of MDMA. Finally, the systemic administration of MDMA produced a 30% decrease in the concentration of ATP in the striatum and hippocampus. These results support the conclusion that MDMA produces a dysregulation of energy metabolism which contributes to the mechanism of MDMA-induced 5-HT neurotoxicity.

Authors+Show Affiliations

College of Pharmacy, University of Cincinnati, 3223, Eden Ave., Cincinnati, OH 45267, USA.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

16098955

Citation

Darvesh, Altaf S., and Gary A. Gudelsky. "Evidence for a Role of Energy Dysregulation in the MDMA-induced Depletion of Brain 5-HT." Brain Research, vol. 1056, no. 2, 2005, pp. 168-75.
Darvesh AS, Gudelsky GA. Evidence for a role of energy dysregulation in the MDMA-induced depletion of brain 5-HT. Brain Res. 2005;1056(2):168-75.
Darvesh, A. S., & Gudelsky, G. A. (2005). Evidence for a role of energy dysregulation in the MDMA-induced depletion of brain 5-HT. Brain Research, 1056(2), 168-75.
Darvesh AS, Gudelsky GA. Evidence for a Role of Energy Dysregulation in the MDMA-induced Depletion of Brain 5-HT. Brain Res. 2005 Sep 21;1056(2):168-75. PubMed PMID: 16098955.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence for a role of energy dysregulation in the MDMA-induced depletion of brain 5-HT. AU - Darvesh,Altaf S, AU - Gudelsky,Gary A, PY - 2005/01/20/received PY - 2005/07/07/revised PY - 2005/07/13/accepted PY - 2005/8/16/pubmed PY - 2005/12/13/medline PY - 2005/8/16/entrez SP - 168 EP - 75 JF - Brain research JO - Brain Res. VL - 1056 IS - 2 N2 - Although the exact mechanism involved in the long-term depletion of brain serotonin (5-HT) produced by substituted amphetamines is not completely known, evidence suggests that oxidative and/or bioenergetic stress may contribute to 3,4-methylenedioxymethamphetamine (MDMA)-induced 5-HT toxicity. In the present study, the effect of supplementing energy substrates was examined on the long-term depletion of striatal 5-HT and dopamine produced by the local perfusion of MDMA (100 microM) and malonate (100 mM) and the depletion of striatal and hippocampal 5-HT concentrations produced by the systemic administration of MDMA (10 mg/kg i.p. x4). The effect of systemic administration of MDMA on ATP levels in the striatum and hippocampus also was examined. Reverse dialysis of MDMA and malonate directly into the striatum resulted in a 55-70% reduction in striatal concentrations of 5-HT and dopamine, and these reductions were significantly attenuated when MDMA and malonate were co-perfused with nicotinamide (1 mM). Perfusion of nicotinamide or ubiquinone (100 microM) also attenuated the depletion of 5-HT in the striatum and hippocampus produced by the systemic administration of MDMA. Finally, the systemic administration of MDMA produced a 30% decrease in the concentration of ATP in the striatum and hippocampus. These results support the conclusion that MDMA produces a dysregulation of energy metabolism which contributes to the mechanism of MDMA-induced 5-HT neurotoxicity. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/16098955/Evidence_for_a_role_of_energy_dysregulation_in_the_MDMA_induced_depletion_of_brain_5_HT_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(05)01048-6 DB - PRIME DP - Unbound Medicine ER -