Potentiation of opioid analgesia in dopamine2 receptor knock-out mice: Evidence for a tonically active anti-opioid system

Michael A. King, Sheri Bradshaw, Albert H. Chang, John E. Pintar, Gavril W. Pasternak

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69 Scopus citations


Dopamine systems are intimately involved with opioid actions. Pharmacological studies suggest an important modulatory effect of dopamine and its receptors on opioid analgesia. We have now examined these interactions in a knock-out model in which the dopamine2 (D2) receptor has been disrupted. Loss of D2 receptors enhances, in a dose-dependent manner, the analgesic actions of the μ analgesic morphine, the κ1 agonist U50,488H and the κ3 analgesic naloxone benzoylhydrazone. The responses to the δ opioid analgesic [D-Pen2, D-Pen5]enkephalin were unaffected in the knock-out animals. Loss of D2 receptors also potentiated spinal orphanin FQ/nociceptin analgesia. Antisense studies using a probe targeting the D2 receptor revealed results similar to those observed in the knock-out model. The modulatory actions of D2 receptors were independent of σ receptor systems because the σ agonist (+)-pentazocine lowered opioid analgesia in all mice, including the D2 knock-out group. Thus, dopamine D2 receptors represent an additional, significant modulatory system that inhibits analgesic responses to μ and κ opioids.

Original languageEnglish (US)
Pages (from-to)7788-7792
Number of pages5
JournalJournal of Neuroscience
Issue number19
StatePublished - Oct 1 2001

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)


  • Analgesia
  • Analgesic
  • Anti-opioid
  • Antisense
  • D receptor
  • Dopamine
  • Dopamine receptor
  • Knock-out
  • Nociception

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