Methamphetamine-induced dopamine transporter complex formation and dopaminergic deficits: the role of D2 receptor activation.

The Journal of Pharmacology and Experimental Therapeutics
Gregory C HadlockAnnette E Fleckenstein

Abstract

Methamphetamine (METH) abuse is a serious public health issue. Of particular concern are findings that repeated high-dose administrations of METH cause persistent dopaminergic deficits in rodents, nonhuman primates, and humans. Previous studies have also revealed that METH treatment causes alterations in the dopamine transporter (DAT), including the formation of higher molecular mass DAT-associated complexes. The current study extends these findings by examining mechanisms underlying DAT complex formation. The association among DAT complex formation and other METH-induced phenomena, including alterations in vesicular monoamine transporter 2 (VMAT2) immunoreactivity, astrocytic activation [as assessed by increased glial fibrillary acidic protein (GFAP) immunoreactivity], and persistent dopaminergic deficits was also explored. Results revealed that METH-induced DAT complex formation and reductions in VMAT2 immunoreactivity precede increases in GFAP immunoreactivity. Furthermore, and as reported previously for DAT complexes, pretreatment with the D2 receptor antagonist eticlopride [S-(-)-3-chloro-5-ethyl-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-hydroxy-2-methoxybenzamide hydrochloride] attenuated the decrease in VMAT2 immunoreactivity...Continue Reading

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Citations

Oct 29, 2011·The Journal of Pharmacology and Experimental Therapeutics·Lisa M McFaddenAnnette E Fleckenstein
Oct 13, 2015·Progress in Neurobiology·Rosario MoratallaMicaela Morelli
Jul 24, 2010·Journal of Neurochemistry·Pei-Wen ChuAnnette E Fleckenstein
Apr 23, 2013·Journal of Internal Medicine·S Ares-SantosR Moratalla
Apr 2, 2014·European Journal of Pharmacology·Michelle G BaladiAnnette E Fleckenstein
Sep 27, 2015·Pharmacological Reviews·Christopher L GermanAnnette E Fleckenstein
Sep 27, 2019·Stress : the International Journal on the Biology of Stress·Hui QiaoShu-Cheng An
Jan 24, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Diego Luis-RaveloTomas Gonzalez-Hernandez
Mar 8, 2014·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Jan BooijPieter Voorn

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