Morphine increases hippocampal viral load and suppresses frontal lobe CCL5 expression in the LP-BM5 AIDS model

J Neuroimmunol. 2014 Apr 15;269(1-2):44-51. doi: 10.1016/j.jneuroim.2014.02.010. Epub 2014 Feb 28.

Abstract

Chronic opiate abuse accelerates the development of cognitive deficits in human immunodeficiency virus (HIV)-1 patients. To investigate morphine's effects on viral infection of the central nervous system, we applied chronic morphine treatment to the LP-BM5 murine acquired immunodeficiency syndrome (MAIDS) model. LP-BM5 infection induces proinflammatory cytokine/chemokine production, correlating to increased blood-brain barrier permeability. Morphine treatment significantly increased LP-BM5 viral load in the hippocampus, but not in the frontal lobe. Morphine reduced the chemokine CCL5 to non-infected levels in the frontal lobe, but not in the hippocampus. These data indicate a region-specific mechanism for morphine's effects on virally-induced neurocognitive deficits.

Keywords: Blood–brain barrier; Claudin-5; Cytokines; HIV encephalitis; Neuroinflammation; Opiate abuse.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / metabolism
  • Animals
  • Chemokine CCL5 / antagonists & inhibitors
  • Chemokine CCL5 / biosynthesis*
  • Frontal Lobe / drug effects
  • Frontal Lobe / metabolism*
  • Frontal Lobe / virology
  • Gene Expression Regulation
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Hippocampus / virology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Morphine / toxicity*
  • Murine Acquired Immunodeficiency Syndrome / metabolism*
  • Viral Load / drug effects*
  • Viral Load / physiology

Substances

  • Ccl5 protein, mouse
  • Chemokine CCL5
  • Morphine