Degeneration of dopaminergic nigrostriatal pathway is generally accepted to be a cause of Parkinson’s disease (PD) motor symptoms such as akinesia, bradykinesia and tremor. Unfortunately the extent of the degeneration does not correlate with tremor occurrence and intensity, therefore cannot explain sufficiently its appearance. Mechanisms leading to induction of tremor are still not explained. Interestingly, image analysis studies have suggested contribution of an increased activity of the cerebellum to the PD tremor. The aim of the present study was to examine whether a selective, partial lesion of dopaminergic structures – the substantia nigra pars compacta (SNc, A9) and retrorubral field (RRF, A8) would influence the tremor behaviour induced by harmaline. Harmaline model of tremor induces an abnormal synchronous activation of the climbing glutamatergic olivo-cerebellar pathway and cerebellar Purkinje cells. 6-OHDA (8 mg /2 ml) was injected unilaterally into the region of the posterior part of the SNc and RRF to induce moderate size of degeneration, similar to early PD. Harmaline was administered in a dose of 7.5 mg/kg i.p. on the 8th day after the operation and tremor of forelimbs, head and trunk was measured. In precise behavioural studies we have found that the lesion of dopaminergic system increased intensity of the tremor induced by harmaline but did not influence its character. Stereological examination of the lesion extent revealed losses of dopaminergic (tyrosine hydroxylase-immunoreactive) neurons in the anterior (30%) and posterior (72%) SNc, as well as in RRF (72% on the average). Levels of dopamine and all its metabolites, as well as noradrenaline concentrations on ipsilateral to lesioned side were moderately decreased in the caudate-putamen, while, dopamine and DOPAC in the anterior cerebellum were increased. In the caudate-putamen, the ipsi/contra ratio of dopamine level correlated negatively, while that of dopamine turnover positively with the tremor intensity. However, in the anterior cerebellum an inverse relationship was found. Moreover, this symptom correlated positively with serotonin level and negatively with the 5-HIAA/serotonin ratio on the contralateral side of the posterior cerebellum. The presented results indicate that modulation of dopaminergic and serotonergic transmissions by the dopaminergic system lesion, modelling early stages of PD, may influence cerebellar mechanisms triggering tremor. The study was supported by the grant of the Ministry of Science and Higher Education No N_N401_570638 and by Statutory Funds of the Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland
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