ABSTRACT
The indole alkaloid harmaline has been to cause tremor and ataxia, and produce cerebellar neurotoxicity in rat. Degeneration of Purkinje cell alligned in narrow parasagittal bands result from excitation of inferior olivary nucleus in harmaline-treated rats. The objective of this study was to investigate the hypothesis that excitation of climbing fiberinduced by harmaline mediates Purkinje cell injury or degeneration. For this purpose, the inferior olive of rats was chemically ablated by using 3-acetyl pyridine, a neurotoxic chemical, and cerebellar damage followed by administration of harmaline was analyzed using immunohistochemical markers for neurons, glial cells. The results demonstrated that a subset of Purkinje cell in the vermis and paravermis degenerated after harmaline treatment, but harmaline produced little or no Purkinje cell degeneration after inferior olivary ablation. These results suggested that harmalineinduced activation of inferior olivary neurons may lead to release of glutamate from climbing fiber synaptic terminal distributed over the Purkinje cells, and may lead to cytotoxic degeneration of Purkinje cells.