Involvement of nitric oxide in development of tail-tremor induced by repeated nicotine administration in rats

Abstract

Daily administration of nicotine (0.5 mg/kg/day s.c.) to rats caused a tremor that appeared only in the tail (tail-tremor) and which became more marked over 8 days. Nitric oxide (NO) synthase inhibitors, N w-nitro- l-arginine (10 mg/kg/day i.p.) or N w-nitro- l-arginine methyl ester (20 and 40 mg/kg/day i.p.), administered each day before nicotine attenuated the development of the tail-tremor. However, neither N w-nitro- l-arginine (2–10 mg/kg i.p.) nor N w-nitro- l-arginine methyl ester (10–40 mg/kg i.p.) affected the tail-tremor that developed after 14 days of repeated nicotine administration. The noncompetitive N-methyl- d-aspartate (NMDA) receptor antagonist, MK-801 ((+)-5-methyl-10,11,-dihydro-5 H-dibenzo[ a, b]cyclohepten-5,10-imine hydrogen maleate) at 0.2 mg/kg/day (i.p.), or competitive antagonist, CPP (3-[(±)-2-carboxypiperazin-4-yl] propyl-1-phosphonic acid) at 2 mg/kg/day (i.p.), administered each day before nicotine attenuated the development of the tail-tremor. MK-801 (0.01–0.2 mg/kg i.p.) but not CPP (0.5–4 mg/kg i.p.) suppressed the tail-tremor that developed after 14 days of repeated nicotine administration. These results suggest that NO formation mediated by NMDA receptors is involved in the mechanisms underlying the tail-tremor induced by the repeated administration of nicotine.