Persistent neuroinflammatory effects of serial exposure to stress and methamphetamine on the blood-brain barrier

Nicole A. Northrop, Bryan K. Yamamoto

Research output: Contribution to journalArticle

46 Scopus citations


Studies of methamphetamine (Meth)-induced neurotoxicity have traditionally focused on monoaminergic terminal damage while more recent studies have found that stress exacerbates these damaging effects of Meth. Similarities that exist between the mechanisms that cause monoaminergic terminal damage in response to stress and Meth and those capable of producing a disruption of the blood-brain barrier (BBB) suggest that the well-known high co-morbidity of stress and Meth could produce long-lasting structural and functional BBB disruption. The current studies examined the role of neuroinflammation in mediating the effects of exposure to chronic stress and/or Meth on BBB structure and function. Rats were pre-exposed to chronic unpredictable stress (CUS) and/or challenged with Meth. Twenty-four hours after the treatment of Meth in rats pre-exposed to CUS, occludin and claudin-5 immunoreactivity were decreased while truncation of β-dystroglycan, as well as FITC-dextran and water extravasation was increased. All changes other than β-dystroglycan and edema persisted 7 days later, occurred with increases in GFAP and COX-2, and were blocked by ketoprofen after Meth treatment. In addition, persistent increases in FITC-dextran extravasation were prevented by treatment with an EP1 receptor antagonist after Meth exposure. The results indicate that CUS and Meth synergize to produce long-lasting structural and functional BBB disruptions that are mediated by cyclooxygenase and protracted increases in inflammation. These results suggest that stress and Meth can synergize to produce a long-lasting vulnerability of the brain to subsequent environmental insults resulting from the persistent breach of the BBB.

Original languageEnglish (US)
Pages (from-to)951-968
Number of pages18
JournalJournal of Neuroimmune Pharmacology
Issue number4
StatePublished - Dec 1 2012
Externally publishedYes


  • Blood-brain barrier
  • Cyclooxygenase
  • Methamphetamine
  • Neuroinflammation
  • Stress

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

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