title: 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.
authors.affiliation: Department of Psychiatry and Neuropsychology, Maastricht University, EURON, P.O. Box 616, 6200 MD Maastricht, The Netherlands. b.scholtissen@np.unimaas.nl
authors.forename: Bart
authors.initials: B
authors.lastname: Scholtissen
authors.forename: Ronald
authors.initials: R
authors.lastname: Deumens
authors.forename: Albert F G
authors.initials: AF
authors.lastname: Leentjens
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmitz
authors.forename: Arjan
authors.initials: A
authors.lastname: Blokland
authors.forename: Harry W M
authors.initials: HW
authors.lastname: Steinbusch
authors.forename: Jos
authors.initials: J
authors.lastname: Prickaerts
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D007150:Immunohistochemistry; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009043:Motor Activity; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D011930:Reaction Time; D012701:Serotonin / Q000502:physiology*
chemical_list: D012701:Serotonin; D016627:Oxidopamine; D007650:Ketanserin; D003913:Dextroamphetamine; D004298:Dopamine