Multiple Administration of Endogenous Amines TIQ and 1MeTIQ Protects Against a 6-OHDA-Induced Essential Fall of Dopamine Release in the Rat Striatum: In Vivo Microdialysis Study

Parkinson's disease (PD) represents one of the neurodegenerative disorders which are caused by degeneration of dopaminergic neurons in the nigrostriatal pathway. Different toxins, e.g., 6-hydroxydopamine (6-OHDA), are used to model PD in animals. 6-OHDA is a neurotoxin which damages catecholaminergic neurons via production of oxygen radicals. Tetrahydroisoquinolines (TIQs) are endogenous amines which are present in the mammalian brain. Some of them, like TIQ and 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), demonstrate neuroprotective properties. These compounds act as reversible MAO inhibitors and this way block free radical formation. To continue our previous experiments, we evaluated the effect of acute and chronic treatment with TIQ and 1MeTIQ on locomotor/exploratory activity and the release of dopamine as well as its metabolite 3-methoxytyramine (3-MT) in the striatum of unilaterally 6-OHDA-lesioned and sham-operated rats using in vivo microdialysis methodology. Additionally, the changes in the concentration of tyrosine hydroxylase in the substantia nigra were measured. A unilateral 6-OHDA lesion in the substantia nigra produces a strong reduction in the release of dopamine (approx. 70%) and 3-MT (approx. 50%) in the rat striatum. This effect was completely inhibited by multiple administration of TIQ and 1MeTIQ. The results obtained from the in vivo microdialysis study suggest that multiple treatment with both endogenous amines, TIQ and 1MeTIQ, protects dopaminergic neurons against a 6-OHDA-induced deficit of dopamine release. Furthermore, these amines were able to maintain physiological functions of striatal dopamine neurons damaged by a unilateral 6-OHDA lesion.