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Enhancement of 3,4-methylenedioxymethamphetamine neurotoxicity by the energy inhibitor malonate.
J Neurochem. 2001 Apr; 77(2):647-54.JN

Abstract

The acute and long-term effects of the local perfusion of 3,4-methylenedioxymethamphetamine (MDMA) and the interaction with the mitochondrial inhibitor malonate (MAL) were examined in the rat striatum. MDMA, MAL or the combination of MAL with MDMA was reverse dialyzed into the striatum for 8 h via a microdialysis probe while extracellular dopamine (DA) and serotonin (5-HT) were measured. One week later, tissue immediately surrounding the probe was assayed for DA and 5-HT tissue content. Local perfusion of MDMA increased DA and 5-HT release but did not produce long-term depletion of DA or 5-HT in tissue. Malonate also increased both DA and 5-HT release but, in contrast to MDMA, produced only long-term depletion of DA. The combined perfusion of MDMA/MAL synergistically increased the release of DA and 5-HT and produced long-term depletion of both DA and 5-HT in tissue. These results support the conclusion that DA, compared with 5-HT, neurons are more susceptible to mitochondrial inhibition. Moreover, MDMA, which does not normally produce DA depletion in the rat, exacerbated MAL-induced DA depletions. The effect of MDMA in combination with MAL to produce 5-HT depletion suggests a role for bio-energetic stress in MDMA-induced toxicity to 5-HT neurons. Overall, these results highlight the importance of energy balance to the function of DA and 5-HT neurons and to the toxic effects of MDMA.

Authors+Show Affiliations

Program in Basic and Clinical Neuroscience, Department of Psychiatry, Case Western Reserve University, Cleveland, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11299327

Citation

Nixdorf, W L., et al. "Enhancement of 3,4-methylenedioxymethamphetamine Neurotoxicity By the Energy Inhibitor Malonate." Journal of Neurochemistry, vol. 77, no. 2, 2001, pp. 647-54.
Nixdorf WL, Burrows KB, Gudelsky GA, et al. Enhancement of 3,4-methylenedioxymethamphetamine neurotoxicity by the energy inhibitor malonate. J Neurochem. 2001;77(2):647-54.
Nixdorf, W. L., Burrows, K. B., Gudelsky, G. A., & Yamamoto, B. K. (2001). Enhancement of 3,4-methylenedioxymethamphetamine neurotoxicity by the energy inhibitor malonate. Journal of Neurochemistry, 77(2), 647-54.
Nixdorf WL, et al. Enhancement of 3,4-methylenedioxymethamphetamine Neurotoxicity By the Energy Inhibitor Malonate. J Neurochem. 2001;77(2):647-54. PubMed PMID: 11299327.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhancement of 3,4-methylenedioxymethamphetamine neurotoxicity by the energy inhibitor malonate. AU - Nixdorf,W L, AU - Burrows,K B, AU - Gudelsky,G A, AU - Yamamoto,B K, PY - 2001/4/12/pubmed PY - 2001/5/18/medline PY - 2001/4/12/entrez SP - 647 EP - 54 JF - Journal of neurochemistry JO - J. Neurochem. VL - 77 IS - 2 N2 - The acute and long-term effects of the local perfusion of 3,4-methylenedioxymethamphetamine (MDMA) and the interaction with the mitochondrial inhibitor malonate (MAL) were examined in the rat striatum. MDMA, MAL or the combination of MAL with MDMA was reverse dialyzed into the striatum for 8 h via a microdialysis probe while extracellular dopamine (DA) and serotonin (5-HT) were measured. One week later, tissue immediately surrounding the probe was assayed for DA and 5-HT tissue content. Local perfusion of MDMA increased DA and 5-HT release but did not produce long-term depletion of DA or 5-HT in tissue. Malonate also increased both DA and 5-HT release but, in contrast to MDMA, produced only long-term depletion of DA. The combined perfusion of MDMA/MAL synergistically increased the release of DA and 5-HT and produced long-term depletion of both DA and 5-HT in tissue. These results support the conclusion that DA, compared with 5-HT, neurons are more susceptible to mitochondrial inhibition. Moreover, MDMA, which does not normally produce DA depletion in the rat, exacerbated MAL-induced DA depletions. The effect of MDMA in combination with MAL to produce 5-HT depletion suggests a role for bio-energetic stress in MDMA-induced toxicity to 5-HT neurons. Overall, these results highlight the importance of energy balance to the function of DA and 5-HT neurons and to the toxic effects of MDMA. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/11299327/Enhancement_of_34_methylenedioxymethamphetamine_neurotoxicity_by_the_energy_inhibitor_malonate_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3042&date=2001&volume=77&issue=2&spage=647 DB - PRIME DP - Unbound Medicine ER -