Performance of movement in hemiparkinsonian rats influences the modifications induced by dopamine agonists in striatal efferent dynorphinergic neurons

Abstract

A previous study of our group demonstrated that movement performance induced by dopamine agonist drugs in hemiparkinsonian rats unilaterally lesioned with 6-hydroxydopamine (6-OHDA), governs the occurrence of a sensitized motor response to a subsequent dopaminergic challenge (priming model). In the present study, we examined the influence of movement performance (rotational behavior) on the molecular events induced by priming in the striatum. To this end, unilaterally 6-OHDA-lesioned rats were primed with apomorphine (0.2mg/kg) in immobilized or freely moving conditions (priming induction) and 3days later the D1 receptor agonist SKF 38393 was administered (priming expression). Evaluation of striatal mRNA for enkephalin and dynorphin, markers of the indirect and direct striatonigral pathways, and of GAD67 showed an increase in dynorphin in primed SKF 38393-treated rats, no matter whether immobilized or freely moving during priming induction, whilst enkephalin and GAD67 did not show any changes. In contrast, evaluation of mRNA for the early gene zif-268 in the striatum showed a generalized increase after administration of SKF 38393, in both primed and unprimed rats. However, examination of zif-268 mRNA at the single-cell level, showed that only dynorphin(+) neurons of primed not immobilized rats displayed a significantly higher number of zif-268-positive silver grains in response to the SKF 38393 challenge. This selective activation of zif-268 in dynorphinergic striatonigral efferent neurons demonstrates that movement performance in response to dopaminergic drug administration under conditions of dopamine denervation is critical for the emergence of neurochemical modifications in selected striatal efferent neurons. Furthermore, these results may provide information on the first initial molecular events taking place in the complex processes that lead to dyskinetic movements in Parkinson's disease.