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Studies on striatal neurotoxicity caused by the 3,4-methylenedioxymethamphetamine/ malonate combination: implications for serotonin/dopamine interactions.
J Psychopharmacol 2006; 20(2):245-56JP

Abstract

The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA) produces long-term toxicity to serotonin (5-HT) neurones in rats, which is exacerbated when combined with the mitochondrial inhibitor malonate. Moreover, MDMA, which does not produce dopamine depletion in the rat, potentiates malonate-induced striatal dopamine toxicity. Because the malonate/MDMA combination acutely causes a synergistic increase of 5-HT and dopamine release, in this study we sought to determine whether pharmacological blockade of MDMA- and/or malonate-induced dopamine release prevents neurotoxicity. Fluoxetine, given 30 min prior to the malonate/MDMA combination, afforded complete protection against 5-HT depletion and reversed MDMA-induced exacerbation of dopamine toxicity found in the malonate/MDMA treated rats. Protection afforded by fluoxetine was not related to changes in MDMA-induced hyperthermia. Similarly, potentiation of malonate-induced dopamine toxicity caused by MDMA was not observed in p-chlorophenylalanine-5-HT depleted rats. Finally, the dopamine transporter inhibitor GBR 12909 completely prevented dopamine neurotoxicity caused by the malonate/MDMA combination and reversed the exacerbating toxic effects of malonate on MDMA-induced 5-HT depletion without significantly altering the hyperthermic response. Overall, these results suggest that the synergic release of dopamine caused by the malonate/MDMA combination plays an important role in the long-term toxic effects. A possible mechanism of neurotoxicity and protection is proposed.

Authors+Show Affiliations

Department of Pharmacology, School of Medicine, University of Navarra, Pamplona, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16510482

Citation

Goñi-Allo, Beatriz, et al. "Studies On Striatal Neurotoxicity Caused By the 3,4-methylenedioxymethamphetamine/ Malonate Combination: Implications for Serotonin/dopamine Interactions." Journal of Psychopharmacology (Oxford, England), vol. 20, no. 2, 2006, pp. 245-56.
Goñi-Allo B, Ramos M, Herv'as I, et al. Studies on striatal neurotoxicity caused by the 3,4-methylenedioxymethamphetamine/ malonate combination: implications for serotonin/dopamine interactions. J Psychopharmacol (Oxford). 2006;20(2):245-56.
Goñi-Allo, B., Ramos, M., Herv'as, I., Lasheras, B., & Aguirre, N. (2006). Studies on striatal neurotoxicity caused by the 3,4-methylenedioxymethamphetamine/ malonate combination: implications for serotonin/dopamine interactions. Journal of Psychopharmacology (Oxford, England), 20(2), pp. 245-56.
Goñi-Allo B, et al. Studies On Striatal Neurotoxicity Caused By the 3,4-methylenedioxymethamphetamine/ Malonate Combination: Implications for Serotonin/dopamine Interactions. J Psychopharmacol (Oxford). 2006;20(2):245-56. PubMed PMID: 16510482.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Studies on striatal neurotoxicity caused by the 3,4-methylenedioxymethamphetamine/ malonate combination: implications for serotonin/dopamine interactions. AU - Goñi-Allo,Beatriz, AU - Ramos,Mar'a, AU - Herv'as,Isabel, AU - Lasheras,Berta, AU - Aguirre,Norberto, PY - 2006/3/3/pubmed PY - 2006/8/10/medline PY - 2006/3/3/entrez SP - 245 EP - 56 JF - Journal of psychopharmacology (Oxford, England) JO - J. Psychopharmacol. (Oxford) VL - 20 IS - 2 N2 - The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA) produces long-term toxicity to serotonin (5-HT) neurones in rats, which is exacerbated when combined with the mitochondrial inhibitor malonate. Moreover, MDMA, which does not produce dopamine depletion in the rat, potentiates malonate-induced striatal dopamine toxicity. Because the malonate/MDMA combination acutely causes a synergistic increase of 5-HT and dopamine release, in this study we sought to determine whether pharmacological blockade of MDMA- and/or malonate-induced dopamine release prevents neurotoxicity. Fluoxetine, given 30 min prior to the malonate/MDMA combination, afforded complete protection against 5-HT depletion and reversed MDMA-induced exacerbation of dopamine toxicity found in the malonate/MDMA treated rats. Protection afforded by fluoxetine was not related to changes in MDMA-induced hyperthermia. Similarly, potentiation of malonate-induced dopamine toxicity caused by MDMA was not observed in p-chlorophenylalanine-5-HT depleted rats. Finally, the dopamine transporter inhibitor GBR 12909 completely prevented dopamine neurotoxicity caused by the malonate/MDMA combination and reversed the exacerbating toxic effects of malonate on MDMA-induced 5-HT depletion without significantly altering the hyperthermic response. Overall, these results suggest that the synergic release of dopamine caused by the malonate/MDMA combination plays an important role in the long-term toxic effects. A possible mechanism of neurotoxicity and protection is proposed. SN - 0269-8811 UR - https://www.unboundmedicine.com/medline/citation/16510482/Studies_on_striatal_neurotoxicity_caused_by_the_34_methylenedioxymethamphetamine/_malonate_combination:_implications_for_serotonin/dopamine_interactions_ L2 - http://journals.sagepub.com/doi/full/10.1177/0269881106063264?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -