Norharman exacerbates 6-hydroxydopamine-induced Parkinson’s disease but cannot establish it alone

Introduction: β-carbolines (BCs) are heterocyclic indole alkaloids found in human body, grilled meat, alcoholic beverages and tobacco smoke. Based on the present reports, there are controversies about the role of these compounds in the pathophysiology of Parkinson' disease (PD). The aim of this study was to investigate the effect of norharman, a BC, in the prevention, exacerbation or creation of PD in 6-hydroxydopamine (6-OHDA) rat model. Methods: In the first part of this study, PD was established in rats by stereotaxic injection of 6-OHDA into the striatum. At the 2nd and 4th weeks post-surgery, apomorphine-induced rotational test was performed. Just before the surgery to the 4th week, after that rats received i.p. daily injections of norharman or its solvent at different doses. In the second part of the study, other groups of rats received daily intraperitoneal injections of norharman at different doses without prior injections of 6-OHDA. Fifteen and 30 days after the beginning of the injections, apomorphine-induced rotational and elevated body swing tests were performed. Results: In the 6-OHDA-induced Parkinsonism rats, daily injection of norharman at doses of 200 and 1000, but not 100 μg/kg, significantly increased apomorphine-induced rotations compared to the control group at the 4th week postsurgery. In the intact rats, daily injection of norharman at doses of 200, 500 and 1000 μg/kg could not produce any PD symptoms in the apomorphine-induced rotational and elevated body swing tests. Conclusion: Longtime exposure to BCs can exacerbate PD but it cannot create the disease.