Thumbnail
Access Restriction
Open

Author Weaver, John ♦ Yang, Yirong ♦ Purvis, Rebecca ♦ Weatherwax, Theodore ♦ Rosen, Gerald M. ♦ Liu, Ke Jian
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword 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
Abstract 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 the 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.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2014-03-01
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 275
Issue Number 2


Open content in new tab

   Open content in new tab