1999-2000 Academic Year Research: Yael Varnado-Rhodes


Mu Opioid Analgesia and Analgesic Tolerance in Two Different Mouse Strains: C57BL/6 and 129/SvJ Mice

Transgenic mice are a useful tool to dissect the genetic basis of behavior. Such mice are often constructed from two distinct mouse strains that differ in genotype. In our initial attempts to understand the cellular and molecular processes controlling opiate tolerance we began comparing nociception in two strains of mice commonly used in knockout studies: C57BL/6 (B6) and 129/SvJ (129). We found that basal nociceptive responses did not differ significantly in B6 and the 129 strains of mice in either the Hargreaves or Hotplate tests. Mice of the 129 strain did have elevated baseline tail flick responses compared to B6 mice likely due to an increase in novelty or restraint stress-induced analgesia. The difference in baseline response latency was not evident after acclimation of the 129 strain to the testing apparatus. In both strains infusion of fentanyl through osmotic mini-pumps produced analgesic tolerance within 35-50 hours in both the Hargreaves and Hotplate tests. However, the 129 strain showed a seven-fold greater sensitivity to subcutaneously injected fentanyl than the B6 mice in the Hotplate test. Fentanyl-induced hyperactivity made the Hargreaves test difficult leading us to use the Hotplate test for future studies of transgenic mice from these strains.

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