RT Journal Article
SR Electronic
T1 Cross-tolerance between mu opioid and alpha-2 adrenergic receptors, but not between mu and delta opioid receptors in the spinal cord of the rat.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 551
OP 558
VO 265
IS 2
A1 E A Kalso
A1 A F Sullivan
A1 H J McQuay
A1 A H Dickenson
A1 B P Roques
YR 1993
UL http://jpet.aspetjournals.org/content/265/2/551.abstract
AB Intrathecal administration of morphine, Tyr-D-Ser(otbu)-Gly-Phe-Leu-Thr or dexmedetomidine for 5 to 10 days rendered rats tolerant to the test drug as measured by both behavioral and electrophysiological tests. Tolerance to the alpha-2 adrenergic agonist dexmedetomidine required a longer induction time and was not as pronounced as the tolerance to the opioid agonists, probably because lower doses of dexmedetomidine relative to the ED50 dose were used to avoid sedation. In the behavioral studies we used the tail-flick test and in the electrophysiological studies recordings were made from dorsal horn nociceptive neurons under halothane anesthesia. After completion of the behavioral testing the same animals were then used in the electrophysiological study. Cross-tolerance developed clearly between the mu opioid agonist morphine and the alpha-2 adrenergic agonist dexmedetomidine, whereas no cross-tolerance was seen between the delta opioid agonist Tyr-D-Ser(otbu)-Gly-Phe-Leu-Thr and either morphine or dexmedetomidine. This is further evidence to support the assumption that in the dorsal horn the mu opioid and the alpha-2 adrenergic receptor are linked functionally, whereas the delta opioid receptor operates independently. These results have also important clinical implications indicating the potential of delta opioid agonists to restore analgesia in a morphine-tolerant patient.