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Title: In vivo evidence of methamphetamine induced attenuation of brain tissue oxygenation as measured by EPR oximetry

Abuse of methamphetamine (METH) is a major and significant societal problem in the US, as a number of studies have suggested that METH is associated with increased cerebrovascular events, hemorrhage or vasospasm. Although cellular and molecular mechanisms involved in METH-induced toxicity are not completely understood, changes in brain O{sub 2} may play an important role and contribute to METH-induced neurotoxicity including dopaminergic receptor degradation. Given that O{sub 2} is the terminal electron acceptor for many enzymes that are important in brain function, the impact of METH on brain tissue pO{sub 2}in vivo remains largely uncharacterized. This study investigated striatal tissue pO{sub 2} changes in male C57BL/6 mice (16–20 g) following METH administration using EPR oximetry, a highly sensitive modality to measure pO{sub 2}in vivo, in situ and in real time. We demonstrate that 20 min after a single injection of METH (8 mg/kg i.v.), the striatal pO{sub 2} was reduced to 81% of the pretreatment level and exposure to METH for 3 consecutive days further attenuated striatal pO{sub 2} to 64%. More importantly, pO{sub 2} did not recover fully to control levels even 24 h after administration of a single dose of METH and continual exposure to METH exacerbates themore » condition. We also show a reduction in cerebral blood flow associated with a decreased brain pO{sub 2} indicating an ischemic condition. Our findings suggests that administration of METH can attenuate brain tissue pO{sub 2}, which may lead to hypoxic insult, thus a risk factor for METH-induced brain injury and the development of stroke in young adults. - Highlights: • Explored striatal tissue pO{sub 2}in vivo after METH administration by EPR oximetry. • pO{sub 2} was reduced by 81% after a single dose and 64% after 3 consecutive daily doses. • pO{sub 2} did not recover fully to control levels even 24 h after a single dose. • Decrease in brain tissue pO{sub 2} may be associated with a decrease in CBF. • Administration of methamphetamine may lead to hypoxic insult.« less
Authors:
 [1] ;  [2] ;  [1] ;  [2] ;  [1] ;  [2] ;  [3] ;  [4] ;  [2] ;  [2] ;  [1] ;  [2] ;  [2]
  1. Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States)
  2. (United States)
  3. Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States)
  4. Center for Biomedical Engineering and Technology, University of Maryland, Baltimore, MD 21201 (United States)
Publication Date:
OSTI Identifier:
22423788
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 275; Journal Issue: 2; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMPHETAMINES; ANIMAL TISSUES; ANOXIA; BLOOD FLOW; BRAIN; ELECTRON SPIN RESONANCE; ENZYMES; HEART; HEMORRHAGE; IN VIVO; INJECTION; INJURIES; ISCHEMIA; LEAD; MICE; OXYGEN; PARTIAL PRESSURE; RECEPTORS; TOXICITY