INVOLVEMENT OF NITRIC-OXIDE IN DEVELOPMENT OF TAIL-TREMOR INDUCED BY REPEATED NICOTINE ADMINISTRATION IN RATS

Daily administration of nicotine (0.5 mg/kg per day s.c.) to rats caus ed a tremor that appeared only in the tail(tail-tremor) and which beca me more marked over 8 days. Nitric oxide (NO) synthase inhibitors, N-W -nitro-L-arginine (10 mg/kg per day i.p.) or N-W-nitro-L-arginine meth yl eater (20 and 40 mg/kg per day i.p.), administered each day before nicotine attenuated the development of the tail-tremor. However, neith er N-W-nitro-L-aginine (2-10 mg/kg i.p.) nor N-W-nitro-L-arginine meth yl eater (10-40 mg/kg i.p.) affected the tail-tremor that developed af ter 14 days of repeated nicotine administration. The noncompetitive N- methyI-D-aspartate (NMDA) receptor antagonist, MK-801 ethyl-10,11,-dih ydro-5H-dibenzo[a,b]cyclohepten-5, 10-imine hydrogen maleate) at 0.2 m g/kg per day (i.p.), or competitive antagonist, CPP (3-[(+/-)-2-carbox ypiperazin-4-yl] propyl-I-phosphonic acid) at 2 mg/kg per day (i.p.), administered each day before nicotine attenuated the development of th e 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 repeat ed nicotine administration. These results suggest that NO formation me diated by NMDA receptors is involved in the mechanisms underlying the tail-tremor induced by the repeated administration of nicotine. (C) 19 97 Elsevier Science B.V.