Assessment of anti-tremorogenic drugs using nicotine-induced tail-tremor model and elucidation of the mechanism

Repeated administration of nicotine causes a tremor only in the tail (tail- tremor) of rats. The tremor is accompanied with locomotor hyperactivity wit hout rigidity and immobility of the whole body, suggesting the involvement of the mechanism associated with the movement. The tail-tremor induced by n icotine was suppressed by nicotinic acethylcholine (nACh) receptor antagoni sts, but not by muscarinic acethylcholine (mACh) receptor antagonists. More over, the tail-tremor was suppressed by beta -adrenoceptor antagonists and benzodizepines. The tremor at rest is observed only in Parkinson's disease, which is improved by the use of mACh receptor antagonists. An essential tr emor is one of the typical tremor connected with the movement (postural tre mor) and improved with beta -adrenoceptor antagonists. These findings and r esults suggest that the nicotine-induced tail-tremor is useful for the stud y of the essential tremor as an animal model. On the other hand, daily admi nistration of nicotine resulted in an augmentation of the tail-tremor. The development of the tail-tremor was suppressed by nACh receptor antagonists, N-methyl-D-aspartate (NMDA) receptor antagonists and nitric oxide (NO) syn thase inhibitors. These results suggest that central nACh receptors are ess ential for the onset and further development of the tail-tremor induced by repeated administration of nicotine, and that NO formation mediated by NMDA receptors is involved in the developmental mechanisms.