PT  - JOURNAL ARTICLE
AU  - J. Paul Hansen
AU  - Evan L. Riddle
AU  - Verónica Sandoval
AU  - Jeffrey M. Brown
AU  - James W. Gibb
AU  - Glen R. Hanson
AU  - Annette E. Fleckenstein
TI  - Methylenedioxymethamphetamine Decreases Plasmalemmal and Vesicular Dopamine Transport: Mechanisms and Implications for Neurotoxicity
AID  - 10.1124/jpet.300.3.1093
DP  - 2002 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1093--1100
VI  - 300
IP  - 3
4099  - http://jpet.aspetjournals.org/content/300/3/1093.short
4100  - http://jpet.aspetjournals.org/content/300/3/1093.full
SO  - J Pharmacol Exp Ther2002 Mar 01; 300
AB  - Administration of a high-dose regimen of methamphetamine (METH) rapidly and profoundly decreases plasmalemmal and vesicular dopamine (DA) transport in the striatum, as assessed in synaptosomes and purified vesicles, respectively. To determine whether these responses were common to other amphetamines of abuse, effects of methylenedioxymethamphetamine (MDMA) on the plasmalemmal DA transporter (DAT) and vesicular monoamine transporter-2 (VMAT-2) were assessed. Similar to effects of METH reported previously, multiple high-dose MDMA administrations rapidly (within 1 h) decreased plasmalemmal DA uptake, as assessed ex vivo in synaptosomes prepared from treated rats. Unlike effects of multiple METH injections, this deficit was reversed completely 24 h after drug treatment. Also in contrast to effects of multiple METH injections, 1) MDMA caused little or no decrease in binding of the DAT ligand WIN35428, and 2) neither prevention of hyperthermia nor prior depletion of DA prevented the MDMA-induced reduction in plasmalemmal DA transport. However, a role for phosphorylation was suggested because pretreatment with protein kinase C inhibitors attenuated the deficit caused by MDMA in an in vitro model system. In addition to affecting DAT function, MDMA rapidly decreased vesicular DA transport as assessed in striatal vesicles prepared from treated rats. Unlike effects of multiple METH injections reported previously, this decrease partially recovered by 24 h after drug treatment. Taken together, these results reveal several differences between effects of MDMA and previously reported METH on DAT and VMAT-2; differences that may underlie the dissimilar neurotoxic profile of these agents. The American Society for Pharmacology and Experimental Therapeutics