Effects of neomycin on the development of tolerance to morphine antinociception

The effects of neomycin on the development of tolerance to morphine antinoc iception were examined in mice. Because neomycin did not readly cross blood brain barrier, we examined the effects of neomycin following systemic, int racerebroventricular (i.c.v.) and intrathecal (i.t.) injections on the morp hine tolerance. Daily subcutaneous (s.c.), i.c.v. and i.t. injections of mo rphine produced tolerance regardless of route of administration. Both i.c.v . and i.t. neomycin, which alone produced no changes in the basal tail flic k latencies, significantly attenuated the development of tolerance to antin ociception 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 antino ciception produced by repeated i.c.v. and i.t. morphine, respectively, whic h were not attenuated by systemic neomycin. This results indicate a potenti al role for neomycin-sensitive Ca2+ channels on the development of toleranc e to the morphine antinoception. (C) 2001 Elsevier Science Inc. All rights reserved.