Evidence for a role of energy dysregulation
in the MDMA-induced depletion of brain 5-HT

by
Darvesh AS, Gudelsky GA.
College of Pharmacy, University of Cincinnati,
3223, Eden Ave., Cincinnati,
OH 45267, USA.
Brain Res. 2005 Aug 11


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 muM) 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 muM) 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.

Club drugs
Abstinence
Parkinson's?
Liver failure
Brain damage?
Kidney damage
Malonate/toxicity
Deaths in New York
Long-term brain damage?
Toxic metabolites of MDMA?
MDMA and sympathetic activity
MDMA and the MAO-b deficient mouse
A toxic intraneuronal metabolite of serotonin?
Electrophysiological evidence of 5-HT damage
Non-neurotoxic and neurotoxic serotonin-releasers
Ecstasy-induced toxicity and the dopamine transporter
5-HT, 5-HIAA, norepinephrine, epinephrine and dopamine


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