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

Abstract

Repeated administration of nicotine causes a tremor only in the tail (tail-tremor) of rats. The tremor is accompanied with locomotor hyperactivity without rigidity and immobility of the whole body, suggesting the involvement of the mechanism associated with the movement. The tail-tremor induced by nicotine was suppressed by nicotinic acethylcholine (nACh) receptor antagonists, but not by muscarinic acethylcholine (mACh) receptor antagonists. Moreover, 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 tremor is one of the typical tremor connected with the movement (postural tremor) and improved with beta-adrenoceptor antagonists. These findings and results suggest that the nicotine-induced tail-tremor is useful for the study of the essential tremor as an animal model. On the other hand, daily administration 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) synthase inhibitors. These results suggest that central nACh receptors are essential 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.