The role of brain acetylcholine in phenol-induced tremor in mice

The relation between phenol-induced tremor and brain acetylcholine levels, and the effects of cholinergic drugs on the tremor were investigated, using male ddY mice weighing 28-35 g. The magnitude of phenol-induced tremor was graded on a 4-point scale: 0, normal; 1, slight; 2, moderate; 3, severe, and acetylcholine levels were measured by high-performance liquid chromatography with electrochemical detection. The magnitude of tremor and the decrease in acetylcholine levels in the striatum and cerebral cortex induced by s.c. injection of phenol (50, 100, 200 mg/kg) were dose-dependent, and both showed parallel time courses. Intracerebroventricular (i.c.v.) injection of phenol (100 micrograms/mouse) caused a decrease in acetylcholine levels in the striatum but did not induce tremor. Intraperitoneal injection of pentobarbital (10 mg/kg), which inhibits the release of acetylcholine, weakened both the magnitude of the tremor and the decrease in acetylcholine levels induced by phenol (200 mg/kg), whereas i.c.v. injection of pentobarbital (120 micrograms/mouse) attenuated the decrease in acetylcholine levels induced by phenol, but did not affect the magnitude of the tremor. Intraperitoneal (20 mg/kg) or i.c.v. (60 micrograms/mouse) injection of mecamylamine further strengthened the tremor. Intraperitoneal (0.3 mg/kg) injection of physostigmine strengthened the tremor, while i.c.v. injection (1 microgram/mouse) caused a reduction in its magnitude. These results suggest that the tremor is caused directly by the phenol-induced increase in acetylcholine release in the peripheral nervous system (motor nerve endings), that the decrease in brain acetylcholine levels may be due to phenol-induced increases in acetylcholine release within the central nervous system, and that the resultant reduction in brain acetylcholine levels indirectly suppresses the tremor.