The impact of 1MeTIQ on the dopaminergic system function in the 6-OHDA model of Parkinson's disease

Pharmacol Rep. 2016 Dec;68(6):1205-1213. doi: 10.1016/j.pharep.2016.08.004. Epub 2016 Aug 13.

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.

Conclusion: 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.

Keywords: 1MeTIQ; 6-OHDA; Neuroprotection; Parkinson’s disease; Rat.

MeSH terms

  • Animals
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Oxidopamine / toxicity*
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / metabolism*
  • Parkinsonian Disorders / prevention & control*
  • Rats
  • Rats, Wistar
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Tetrahydroisoquinolines / pharmacology
  • Tetrahydroisoquinolines / therapeutic use*

Substances

  • Neuroprotective Agents
  • Tetrahydroisoquinolines
  • 1-methyl-1,2,3,4-tetrahydroisoquinoline
  • Oxidopamine
  • Dopamine