title: Comparison of the Effects of Acute and Chronic Administration of Tetrahydroisoquinoline Amines on the In Vivo Dopamine Release: A Microdialysis Study in the Rat Striatum.
abstract: The etiology of Parkinson's disease (PD) may involve endogenous and exogenous factors. 1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), which was shown to be neurotoxic for dopaminergic neurons, is one of such factors, thus it can be used to construct an animal model of PD. In contrast, 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) produce neuroprotective effects acting as monoamino oxidase (MAO) inhibitors and free radical scavengers that reduce oxidative stress in the mammalian brain. In this study, we aimed to investigate the effects of neuroprotective compounds, TIQ and 1MeTIQ, on the dopamine release in vivo in an animal model of PD induced by chronic administration of 1BnTIQ (25 mg/kg i.p.). Using an in vivo microdialysis methodology, we measured the impact of both acute and chronic treatment with TIQ and 1MeTIQ (50 mg/kg i.p.) on 1BnTIQ-induced changes in dopamine release in the rat striatum. Additionally, the behavioral test was carried out to check the influence of repeated administrations of the investigated compounds on the locomotor activity of rats. The behavioral studies showed that the chronic administration of 1BnTIQ produced a significant elevation of exploratory locomotor activity, and both the investigated amines, TIQ and 1MeTIQ, administered together with 1BnTIQ completely prevented 1BnTIQ-produced hyperactivity. The in vivo microdialysis studies demonstrated that the chronic treatment with 1BnTIQ caused a significant and long-lasting increase in the dopamine release (approximately 300 %) to the extracellular space in the rat striatum, which was demonstrated in the basal samples 24 h after 1BnTIQ injection. The combined chronic administration of 1BnTIQ and the investigated compounds, TIQ or 1MeTIQ, completely antagonized the 1BnTIQ-induced essential disturbances of the dopamine releasing to the extracellular space in the striatum. In conclusion, we suggest that higher concentrations of 1BnTIQ in the brain produced distinct impairment in the dopamine release, whereas TIQ and 1MeTIQ (compounds with previously revealed neuroprotective properties) completely prevented 1BnTIQ-induced abnormalities in the function of dopamine neurons and restored the dopamine release to the control values.
authors: Department of Neurochemistry, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland. wasik@if-pan.krakow.pl.
authors: Agnieszka
authors: A
authors: Wąsik
authors: Department of Neurochemistry, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland.
authors: Irena
authors: I
authors: Romańska
authors: Department of Neurochemistry, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland.
authors: Lucyna
authors: L
authors: Antkiewicz-Michaluk
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism*; D015259:Dopamine Agents / Q000008:administration & dosage*; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000378:metabolism; D017208:Rats, Wistar; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D015259:Dopamine Agents; D018696:Neuroprotective Agents; D044005:Tetrahydroisoquinolines; C050386:1-methyl-1,2,3,4-tetrahydroisoquinoline; C014843:1,2,3,4-tetrahydroisoquinoline; C001746:3-methoxytyramine; D004298:Dopamine; C084924:1,2,3,4-tetrahydro-1-(phenylmethyl)isoquinoline
keywords: Dopamine release; Microdialysis study; Rat striatum; Tetrahydroisoquinolines