Long term exposure to norharman exacerbates 6-hydroxydopamine-induced parkinsonism: possible involvement of L-type Ca2+ channels

Behavioural Brain Research
Hashem Haghdoost-YazdiHassan Jahanihashemi

Abstract

beta-Carbolines (BCs) are considered as endogenous neurotoxins that may contribute to the pathogenesis of Parkinson's disease (PD). However, several lines of evidences show that these compounds have neuroprotective effect. This study was designed to assess effect of long term exposure to norharman, a BC compound which in mammalian brain occurs at high levels in the substantia nigra, on the progress of parkinsonism induced by 6-hydroxydopamine (6-OHDA). Animals were daily treated by norharman at doses 100, 200 and 1000microg/kg (i.p.) just before to four weeks after the intrastriatal injection of 6-OHDA. Statistical analysis of apomorphine-induced rotation tests demonstrates that treatment by norharman at doses 200 and 1000microg/kg for four weeks exacerbates significantly behavioral symptoms of the parkinsonism. To explore mechanisms by which norharman affects nigral dopaminergic cells, we studied the role of L-type Ca2+ channels. For this purpose, animals were daily treated with either L-type Ca2+ channel blocker of nifedipine at doses 2 and 5mg/kg (i.p.) or nifedipine together with norharman before to four weeks after the 6-OHDA injection. While treatment with nifedipine improved behavioral symptoms of the parkinsonism, treat...Continue Reading

References

Aug 1, 1979·CRC Critical Reviews in Toxicology·T Sugimura, M Nagao
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Mar 10, 2000·European Journal of Pharmacology·C C ShiC F Chen

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Citations

Jul 14, 2012·Neurotoxicology and Teratology·Mohammad Hossein EsmaeiliHashem Haghdoost-Yazdi
Jun 2, 2015·Chemical Communications : Chem Comm·Zhenhui QiChristoph A Schalley
Oct 30, 2016·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Tomás Herraiz
Jul 6, 2011·Acta Crystallographica. Section C, Crystal Structure Communications·Robert J Thatcher, Richard E Douthwaite
Nov 1, 2013·Molecular Pharmaceutics·Celesztina DomonkosFerenc Zsila

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