6-OHDA injections into A8-A9 dopaminergic neurons modelling early stages of Parkinson's disease increase the harmaline-induced tremor in rats

The aim of the present study was to examine the influence of a unilateral 6-hydroxydopamine (6-OHDA)-induced partial lesion of both the substantia nigra pars compacta (SNc, A9) and retrorubral field (RRF, A8) on the tremor evoked by harmaline. 6-OHDA (8 mu g/2 mu l) was injected unilaterally into the region of the posterior part of the SNc and RRF. Harmaline was administered in a close of 7.5 mg/kg ip on the eighth day after the operation and tremor of forelimbs, head and trunk was measured. We found that the lesion 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, were ipsilaterally moderately decreased in the caudate-putamen in the lesioned animals, however, 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 the serotonin level and negatively with the 5-HIAA/serotonin ratio on the contralateral side of the posterior cerebellum. The present results seem to indicate that the modulation of dopaminergic and serotonergic transmissions by the lesion modelling early stages of Parkinson's disease may influence tremor triggered in the cerebellum. (C) 2012 Elsevier B.V. All rights reserved.