Functional investigations into the role of dopamine and serotonin in partial bilateral striatal 6-hydroxydopamine lesioned rats

Abstract

In Parkinson's disease (PD), several neurotransmitter systems, such as the dopaminergic and serotonergic system, show signs of degeneration. This led to the suggestion that alterations in the serotonergic system play a role in the pathophysiology of PD. Partial bilateral dopaminergic lesions of the caudate putamen complex (CPu) of rats induced by 6-hydroxydopamine (6-OHDA) produce behavioral symptoms mimicking PD. In the present study, the role of serotonin and dopamine was investigated both behaviorally and neuroanatomically. In a reaction time task, motor initiation and motor performance were impaired in the lesioned animals compared to controls. The performance of rats treated with d-amphetamine or serotonergic ligands (DOI and ketanserin) in the reaction time task indicated that 5-HT and DA appear to be agonistically related in the CPu. The relation was the same in both control and 6-OHDA lesioned rats. 12 weeks after lesioning, motor initiation recovered, whereas motor performance did not. Parallel to the behavioral study, a second group of animals was lesioned and, at 3 days, 6 weeks and 12 weeks after lesioning, a subgroup was killed to obtain a qualitative indication of the degree of 6-OHDA lesion. Over the three time points, a substantial recovery of tyrosine hydroxylase staining in the CPu was visible. Taken together, since serotonergic ligands have the same effect as dopaminergic ligands on reaction time responding indicated that 5-HT and DA release are agonistically linked in control and 6-OHDA lesioned rats.