ROLE OF CENTRAL NICOTINIC AND BETA-ADRENERGIC RECEPTORS IN THE ONSET AND FURTHER DEVELOPMENT OF TAIL TREMOR INDUCED BY REPEATED NICOTINE ADMINISTRATION TO RATS

The effects of nicotinic and beta-adrenergic receptor antagonists on t ail-tremor induced by repeated nicotine administration were investigat ed in rats. The daily administration of nicotine (0.5 mg/kg/day, s.c.) for 8 days resulted in an augmentation of tail-tremor. However, repea ted administration of dimethyl phenyl piperazinium iodide (1 mg/kg/day , s.c.) for 8 days did not cause tail-tremor. Mecamylamine (0.5 mg/kg, i.p), administered before the nicotine injection on each day, abolish ed the tail-tremor. After discontinuation of the mecamylamine treatmen t, nicotine injections caused tail-tremor augmentation. Propranolol (2 0 mg/kg, i.p.), administered before the nicotine on each day, suppress ed the appearance of tail-tremor. After the discontinuation of propran olol treatment, the degree of tail-tremor induced by a single injectio n of nicotine on day 9 was much greater in the propranolol-treated gro up than in the saline-treated control group. Neither carteolol (20 mg/ kg, i.p.) nor metoprolol (20 mg/kg, i.p.) treatment showed such effect s, Intraspinal injection of 6-hydroxydopamine markedly enhanced the ta il-tremor induced on the first day of nicotine injection. This effect became more intense on subsequent administration of nicotine. The enha nced tail-tremor following 6-hydroxydopamine treatment was abolished b y mecamylamine (0.5 and 1 mg/kg, i.p.), and was suppressed by proprano lol (5-20 mg/kg, s.c.) in a dose-dependent manner. These results sugge st that central nicotinic receptors are essential for the onset and fo r the further development of tail-tremor induced by the repeated admin istration of nicotine, and that beta(2)-adrenoceptors are associated w ith the tremor mechanism. Moreover, spinal noradrenergic mechanisms ma y be involved in the manifestation of this phenomenon.