A species-specific difference in the effects of harmaline on the rodent olivocerebellar system

The rodent model of harmaline-induced tremor has been widely used for experimental analysis of tremor. Activation of the olivocerebellar system plays a key role in tremor-generating mechanisms. One undetermined problem is whether there are species-specific differences in effects of harmaline. The present study investigated effects of harmaline on olivocerebellar systems of mice and rats. Systemic administration of harmaline, but not vehicle, produced generalized, high-frequency tremors in both types of rodents. Immunohistochemical studies revealed significant degeneration of Purkinje cells that was associated with activated microgliosis in the cerebellar cortex, following administration of harmaline in rats but not in mice. However, in mice but not rats, microgliosis was induced following administration of harmaline in the inferior olivary nucleus (ION), particularly in its caudal and medial subdivisions. Numbers of neurons in the mouse ION did not decrease, suggesting the possibility that microgliosis in ION might not be a simple neurotoxic effect. Presumably, differences in sensitivity of Purkinje cells between rats and mice may be related to differences in functional alterations in their respective olivocerebellar systems induced by harmaline. Recognition of these species-specific differences in the response of the olivocerebellar system to harmaline is an important consideration for experimental analysis of the rodent model of tremors.