Regulation of nicotine-induced tremor by the dopaminergic nervous system

Abstract

Nicotine excites the inferior olive (IO) neurons and induces kinetic tremor via activating α7 nACh receptors. Meanwhile, nicotine is also known to enhance dopamine release by activating presynaptic nACh receptors, but the role of dopaminergic system in regulating nicotine-induced tremor remains unknown. Here, we investigated the effect of various dopamine receptor antagonists on nicotine-induced tremor in mice and rats. Animals were pretreated with dopamine antagonists 15 min before nicotine (1 mg/kg) injection. Nicotine tremor was significantly facilitated by the selective D_1/5 antagonist SCH-23390 while it was significantly inhibited by the D₃ selective antagonist U-99194. Neither D₂ (L-741,626) nor D₄ antagonist (L-745,870) affected nicotine tremor. In addition, microinjection of SCH-23390 into the IO tended to enhance nicotine tremor, but its injection into the striatum showed no effect. Microinjection of U-99194 into the IO or the striatum did not change nicotine tremor, however, its injection into the cerebellum significantly attenuated nicotine tremor. These results suggest that the dopaminergic system regulates nicotine-induced tremor biphasically, D₃ receptors in the cerebellum being facilitatory and D_1/5 receptors in the IO inhibitory.