An influence of lesions of the catecholaminergic cerebellar innervation on the harmaline-induced tremor in rats

Recent studies have suggested a crucial role of the cerebellum in different forms of tremor. Abnormal synchronous activation of the glutamatergic olivo-cerebellar pathway and Purkinje cells results in the essential tremor in humans and the harmaline-induced tremor in animals. Moreover, an increased neuronal activity of the cerebellum has been found to contribute to the tremor in Parkinson’s disease (PD). Since the cerebellum receives dopaminergic and noradrenergic pathways arising from regions affected in PD, the aim of the present study was to examine a contribution of the cerebellar catecholaminergic innervation to the harmaline-induced tremor in rats. Rats were bilaterally injected into the cerebellar vermis (lobules 8–10) with 6-hydroxydopamine (6-OHDA) (8 μg/0.5 μl) either alone or this treatment was preceded by desipramine (15 mg/kg i.p.). Harmaline was administered at a dose of 7.5 mg/kg i.p. on the 9th post-operative day. Tremor of forelimbs was measured as a number of episodes. After completion of behavioural experiments rats were killed by decapitation and the levels of monoamines and their metabolites were measured by HPLC in lobules 1–3, 4–7 and 8–10 of the cerebellum. 6-OHDA injected alone decreased the noradrenaline level by ca. 40–80% in the cerebellum and enhanced the harmaline-induced tremor. When 6-OHDA administration was preceded by desipramine, it decreased dopaminergic transmission in some regions of the cerebellum but induced its compensatory activation in others. Finally no influence of the latter treatment on the tremor induced by harmaline was observed. The present study indicates that the noradrenergic innervation of the cerebellum plays an inhibitory role in the harmaline-induced tremor. The study was supported by the grant of the Ministry of Science and Higher Education No N N401 570638, and partly by Statutory Funds of the Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland.