The Journal of Neuroscience, October 1, 2001, 21(19):7788-7792
Potentiation of Opioid Analgesia in Dopamine2
Receptor Knock-Out Mice: Evidence for a Tonically Active Anti-Opioid
System
Michael A.
King1,
Sheri
Bradshaw2,
Albert H.
Chang1,
John E.
Pintar2, and
Gavril W.
Pasternak1
1 Laboratory of Molecular Neuropharmacology, Memorial
Sloan-Kettering Cancer Center, New York, New York 10021, and
2 Department of Neuroscience and Cell Biology, Robert Wood
Johnson Medical School, University of Medicine and Dentistry of New
Jersey, Piscataway, New Jersey 08854
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 
1 agonist U50,488H and the
3 analgesic naloxone benzoylhydrazone. The responses to
the 
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 
receptor systems because the 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 opioids.
Key words:
analgesia; dopamine; dopamine receptor; D2 receptor; knock-out; antisense; anti-opioid; nociception; analgesic
Copyright © 2001 Society for Neuroscience 0270-6474/01/21197788-05$05.00/0
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