PREVIOUS reports have suggested that tolerance to the antinociceptive
effects of morphine does not develop in the formalin test. To re-exami
ne these findings, morphine was administered via multiple injections o
r continuous infusion from 0 to 4 days prior to testing with either th
e formalin or tail-flick test. Following twice daily injections (5.0 m
g kg(-1) s.c.), significant tolerance developed within 2 days with the
formalin test but not until day 4 with the tail-flick test. Significa
nt tolerance was noted with both tests 4 days following the implantati
on of osmotic minipumps (10 mg kg(-1) day(-1), s.c.). We conclude that
in mice, tolerance to the analgesic effects of morphine develops rapi
dly with the formalin test.