title: The impact of 1MeTIQ on the dopaminergic system function in the 6-OHDA model of Parkinson's disease.
abstract: BACKGROUND
  Parkinson's disease (PD) is a progressive neurodegenerative disorder which is caused by degeneration of dopaminergic neurons of the nigrostriatal pathway. As a model of PD we used 6-hydroxydopamine (6-OHDA) which exerts toxic effects on catecholaminergic neurons and 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) as neuroprotective compound. The aim of the present study, was to investigate the potential neuroprotective properties of 1MeTIQ against 6-OHDA-induced neurotoxic effects in the rat.
  
  
  METHODS
  In the behavioral study, we measured locomotor activity and catalepsy. In the biochemical studies using HPLC methodology, we analyzed the concentration of dopamine and its metabolites in rat brain.
  
  
  RESULTS
  Behavioral tests showed that 6-OHDA decreased rat locomotor activity and produced an increase of catalepsy. These effects did not blocked by 1MeTIQ injections. Biochemical studies indicated that 6-OHDA lesion significantly reduced the concentration of dopamine and its metabolites in the nigro-striatal pathway in the lesioned (ipsilateral) side. Moreover, 6-OHDA induced an increase in the rate of dopamine oxidation. Both acute and chronic administration of 1MeTIQ did not reverse the effects of 6-OHDA lesion on the ipsilateral side, however, it produced a significant elevation of the dopamine concentration in the contralateral side. It is evident that multiple treatments with 1MeTIQ stimulate undamaged neurons to increased activity.
  
  
  CONCLUSIONS
  1MeTIQ was shown to possess neuroprotective potential to the dopaminergic neurons damaged by 6-OHDA lesion. This compound has a protective effect but does not have neurorestorative capacity. It does not reverse damage already caused but will maintain the function and activity of undamaged dopamine neurons at physiological level.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Neurochemistry, 31-343 Kraków, Smętna street 12, Poland. Electronic address: wasik@if-pan.krakow.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wąsik
authors.affiliation: Faculty of Biotechnology and Horticulture, University of Agriculture, Kraków, Poland.
authors.forename: Dawid
authors.initials: D
authors.lastname: Polak
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Neurochemistry, 31-343 Kraków, Smętna street 12, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Romańska
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Neurochemistry, 31-343 Kraków, Smętna street 12, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Michaluk
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Neurochemistry, 31-343 Kraków, Smętna street 12, Poland.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Antkiewicz-Michaluk
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016627:Oxidopamine / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D044005:Tetrahydroisoquinolines / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D044005:Tetrahydroisoquinolines; C050386:1-methyl-1,2,3,4-tetrahydroisoquinoline; D016627:Oxidopamine; D004298:Dopamine
keywords: 1MeTIQ; 6-OHDA; Neuroprotection; Parkinson’s disease; Rat