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Chronic methamphetamine exposure prior to middle cerebral artery occlusion increases infarct volume and worsens cognitive injury in Male mice

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Abstract

Emerging evidence indicates that methamphetamine (MA) abuse can impact cardiovascular disease. In humans, MA abuse is associated with an increased risk of stroke as well as an earlier age at which the stroke occurs. However, little is known about how chronic daily MA exposure can impact ischemic outcome in either humans or animal models. In the present study, mice were injected with MA (10 mg/kg, i.p.) or saline once daily for 10 consecutive days. Twenty-four hours after the final injection, mice were subjected to transient middle cerebral artery occlusion (tMCAO) for one hour followed by reperfusion. Mice were tested for novel object memory at 96 h post-reperfusion, just prior to removal of brains for quantification of infarct volume using 2,3,5-Triphenyltetrazolium Chloride (TTC) staining. Mice treated with MA prior to tMCAO showed decreased object memory recognition and increased infarct volume compared to saline-treated mice. These findings indicate that chronic MA exposure can worsen both cognitive and morphological outcomes following cerebral ischemia.

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Acknowledgments

The authors acknowledge Ansgar Brambrink, Helmi Lutsep, and Peter Beninato for valuable discussions about stroke data in humans and Kristen Zuloaga for her help in designing the experiments. Funding provided by NIDA T32DA007262 and the OHSU development account of Dr. Raber.

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Authors and Affiliations

  1. Department of Behavioral Neuroscience, Oregon Health and Science University, 3181 SW S Jackson Pk Rd, Portland, OR, 97239, USA

    Damian G. Zuloaga, Sydney Weber, Gregory P. Mark, Stephanie J. Murphy & Jacob Raber

  2. Departments of Neurology and Radiation Medicine, Oregon Health and Science University, Portland, OR, 97239, USA

    Jacob Raber

  3. Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Portland, OR, 97239, USA

    Jianming Wang & Jacob Raber

  4. Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR, 97239, USA

    Stephanie J. Murphy

  5. Department of Psychology, University at Albany, SUNY, 1400 Washington Ave, Albany, NY, 12222, USA

    Damian G. Zuloaga

Authors
  1. Damian G. Zuloaga
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  2. Jianming Wang
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  3. Sydney Weber
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  4. Gregory P. Mark
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  5. Stephanie J. Murphy
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  6. Jacob Raber
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Correspondence to Damian G. Zuloaga or Jacob Raber.

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Zuloaga, D.G., Wang, J., Weber, S. et al. Chronic methamphetamine exposure prior to middle cerebral artery occlusion increases infarct volume and worsens cognitive injury in Male mice. Metab Brain Dis 31, 975–981 (2016). https://doi.org/10.1007/s11011-016-9808-z

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  • DOI: https://doi.org/10.1007/s11011-016-9808-z

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