Effects of neomycin on the development of tolerance to morphine antinociception.

The effects of neomycin on the development of tolerance to morphine antinociception were examined in mice. Because neomycin did not readly cross blood brain barrier, we examined the effects of neomycin following systemic, intracerebroventricular (i.c.v.) and intrathecal (i.t.) injections on the morphine tolerance. Daily subcutaneous (s.c.), i.c.v. and i.t. injections of morphine produced tolerance regardless of route of administration. Both i.c.v. and i.t. neomycin, which alone produced no changes in the basal tail flick latencies, significantly attenuated the development of tolerance to antinociception produced by repeated systemic morphine, while intraperitoneal (i.p.) administration of neomycin did not affect morphine tolerance. Further, i.c.v. and i.t. neomycin attenuated the development of tolerance to antinociception produced by repeated i.c.v. and i.t. morphine, respectively, which were not attenuated by systemic neomycin. This results indicate a potential role for neomycin-sensitive Ca2+ channels on the development of tolerance to the morphine antinoception.