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Suppression of endogenous proliferator-activated receptor gamma increases vulnerability to methamphetamine –induced injury in mouse nigrostriatal dopaminergic pathway

Wednesday, October 26, 2011 — Poster Session IV

2:00 p.m. – 4:00 p.m.

Natcher Conference Center



* FARE Award Winner


  • SJ Yu
  • H Shen
  • BK Harvey
  • Y Wang


Repeated administration of high doses of methamphetamine induces dopaminergic degeneration and reduction in locomotor activity. The purpose of this study was to examine the role of endogenous peroxisome proliferator-activated receptor gamma (PPARr) in protecting against methamphetamine toxicity. Adeno-associated virus (AAV) encoding the Cre recombinase gene was injected into the left substantia nigra of loxP-PPARr or wild type mice. Animals were treated with high doses of methamphetamine 1-month after viral injection. Administration of AAV-Cre selectively removed PPARr in left nigra in loxP-PPARr mice but not in the wild type mice. The loxP-PPARr/AAV-Cre mice that received methamphetamine showed a significant reduction in rotarod time. In vivo voltammetry was used to examine dopamine release/clearance and at 2 months after methamphetamine injection. The peak of dopamine release induced by local application of KCl and the rate of dopamine clearance were significantly attenuated in the left striatum of loxP-PPARr/AAV-Cre animals. Tyrosine hydroxylase immunoreactivity was reduced in the left, compared to right, nigra and dorsal striatum in loxP-PPARr/AAV-Cre mice receiving methamphetamine. Our data suggest that a deficiency in PPARr increases vulnerability to high doses of methamphetamine. Endogenous PPARr may play an important role in reducing methamphetamine toxicity in vivo.

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