Functional studies on monoaminergic transmitter release in parkinsonism

1. In vivo pulse voltammetry and apomorphine induced circling behaviour were used to study the effect of antiparkinsonian drugs and neurotoxins on striatal, extraneuronal dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations which are a measure of dopamine (DA) release/DA metabolism and serotonin (5-HT) release, respectively. 2. The DA precursor dihydroxyphenylalanine (DOPA, i.p.) increased extraneuronal DOPAC and reduced 5-HIAA levels whereas the opposite effect was induced by the 5-HT precursor 5-hydroxytryptophan (5-HTP, i.p.). Tryptophan, i.p., decreased the extraneuronal DOPAC levels without significant effect on 5-HT release. 3. The monoamine oxidase (MAO) inhibitors pargyline, i.p., and deprenyl, i.p., as well as the DA agonist apomorphine, i.p., decreased the catechol signal. The DA antagonist haloperidol, i.p., increased extraneuronal DOPAC. 4. In longterm studies unilateral application of the neurotoxins 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetra-hydroxypyridine (MPTP), and 1-methyl-4-phenylpyridinium cation (MPP+) into the substantia nigra pars compacta abolished the DOPAC signal in the striatum at the lesioned side. This effect can be partially or fully restored by DOPA depending on the time elapsed after neurotoxin administration. 5. In accordance with the voltammetric recorded unilateral lesion of the dopaminergic system the apomorphine stimulated circling behaviour was significantly enhanced in MPTP and MPP+ treated rats as compared with controls. 6. The results obtained indicate that antiparkisonian drugs and neurotoxins besides their effect on total catecholamine and 5-HT concentrations change specifically the extraneuronal levels of the transmitter (metabolites). Moreover the results suggest that neurotoxin-treated rats can be used as a model to study Parkinson-like effects with regard to the pathogenesis and treatment of this disease.