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 language||English (US)|
|Number of pages||5|
|Journal||Journal of Neuroscience|
|State||Published - Oct 1 2001|
All Science Journal Classification (ASJC) codes
- D receptor
- Dopamine receptor