Mi. Damaj et Br. Martin, TOLERANCE TO THE ANTINOCICEPTIVE EFFECT OF EPIBATIDINE AFTER ACUTE AND CHRONIC ADMINISTRATION IN MICE, European journal of pharmacology, 300(1-2), 1996, pp. 51-57
Epibatidine is a novel potent antinociceptive agent that acts through
nicotinic receptors. In this study we investigated the development of
tolerance to the antinociceptive effects of epibatidine enantiomers af
ter acute and chronic administration in mice using the tail-flick test
. Contrary to nicotine, mice treated with epibatidine enantiomers at d
ifferent times and doses did not develop significant tolerance after s
.c. acute nor after repeated injections. In mice that chronically rece
ived (+)-epibatidine, no significant tolerance was seen after acute ch
allenge with (+)-epibatidine. However, a significant shift in (-)-epib
atidine's dose-response curve was obtained in animals that received (-
)-epibatidine. In nicotine-tolerant animals, no significant tolerance
was seen after acute challenge with (+)-epibatidine. However, the anim
als were less sensitive to the acute (-)-epibatidine challenge. Our re
sults show that development of tolerance to epibatidine antinociceptiv
e effects has a different profile and characteristics than that found
for nicotine.