Opioid activation of toll-like receptor 4 contributes to drug reinforcement.

  title={Opioid activation of toll-like receptor 4 contributes to drug reinforcement.},
  author={Mark R Hutchinson and Alexis L Northcutt and Takato Hiranita and X Wang and Susannah S. Lewis and Jean-L{\'e}on Thomas and K van Steeg and Theresa A. Kopajtic and Lisa Carole Loram and C Sfregola and Erika L Galer and N E Miles and Sondra T. Bland and Jos{\'e} Amat and Robert R. Rozeske and Thomas M Maslanik and Timothy R Chapman and Keith A Strand and Monika Fleshner and Ryan K. Bachtell and Andrew Alexander Somogyi and Hulian Yin and Jonathan Katz and Kenner C. Rice and Steven F. Maier and Linda R. Watkins},
  journal={The Journal of neuroscience : the official journal of the Society for Neuroscience},
  volume={32 33},
Opioid action was thought to exert reinforcing effects solely via the initial agonism of opioid receptors. Here, we present evidence for an additional novel contributor to opioid reward: the innate immune pattern-recognition receptor, toll-like receptor 4 (TLR4), and its MyD88-dependent signaling. Blockade of TLR4/MD2 by administration of the nonopioid, unnatural isomer of naloxone, (+)-naloxone (rats), or two independent genetic knock-outs of MyD88-TLR4-dependent signaling (mice), suppressed… CONTINUE READING
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