title: Methamphetamine-induced vascular changes lead to striatal hypoxia and dopamine reduction.
abstract: Methamphetamine (meth) is a potent psychostimulant known to cause neurotoxicity. Clinical reports suggest meth abuse is a risk factor for Parkinson's disease. We investigated changes in the blood-brain barrier and cerebral vasculature as a mechanism underlying this risk in rats treated acutely and trained to self-administer meth. We observed blood-brain barrier leakage in rats treated acutely with meth. Hypoperfusion in the striatum was detected with acute and chronic meth treatment and was associated with hypoxia. This was correlated with reductions in striatal tyrosine hydroxylase in rats trained to self-administer meth. These findings suggest a new mechanism of meth-induced neurotoxicity involving striatal vasoconstriction resulting in hypoxia and dopamine reductions leading to an increased risk for Parkinson's disease for meth abusers.
authors: Department of Pharmacology and the Center for Compulsive Behaviors and Addiction, Rush University, Robert H. and Terri Cohn Research Building, 1735 West Harrison Street, Chicago, IL 60612, USA. sharanya_m_kousik@rush.edu
authors: Sharanya M
authors: SM
authors: Kousik
authors: Steven M
authors: SM
authors: Graves
authors: T Celeste
authors: TC
authors: Napier
authors: Chaohui
authors: C
authors: Zhao
authors: Paul M
authors: PM
authors: Carvey
mesh_terms: D019969:Amphetamine-Related Disorders / Q000150:complications / Q000503:physiopathology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002561:Cerebrovascular Disorders / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004298:Dopamine / Q000172:deficiency*; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D002534:Hypoxia, Brain / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008694:Methamphetamine / Q000633:toxicity; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D008694:Methamphetamine; D016650:Fluorescein-5-isothiocyanate; D004298:Dopamine