Intracerebral injection of low amounts of norharman induces moderate Parkinsonism-like behavioral symptoms in rat

β-Carbolines (BCs) are considered to be endogenous toxins and have been proposed as possible causative candidates inducing Parkinson's disease (PD). However, there is controversy about the effect and also effective dose of these compounds in the etiology of PD. This study was designed to further examine the effect of norharman (NH), a BC which in mammalian brain occurs at high levels in the substantia nigra, on the development of Parkinsonism-like behaviors in rats. A small amount (4 μl) of NH solution at 2 or 200 ng/ml was unilaterally injected into either striatum or substantia nigra (SN) by stereotaxic surgery. The development of Parkinsonism was assessed by three conventional behavioral tests, compared to the effects of unilateral 6-hydroxydopamine (6-OHDA) — induced lesions in the nigrostriatal pathway. An apomorphine‐induced rotational test revealed no Parkinsonism‐like behavior in the NH treated groups. However, rats that received the high concentration of NH into their SN showed significant biased swings in the elevated body swing test. In a rotarod test, NH treated groups showed relatively weak motor performance and their learning patterns were close to that of the 6-OHDA treated rats. Considering that the rotational test is only valid in animals with severe Parkinsonism, but time spent on the rotating rod correlates inversely with severity of Parkinsonism, our results indicate that a single exposure to low amounts of NH is effective in producing moderate Parkinsonism-like behavioral symptoms, possibly through a neurotoxic effect of this agent on the SN dopaminergic neurons.

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► Intracerebral injection of norharman induced Parkinsonism-like behavior in rats.
► This effect was observed after a single injection of low amounts of norharman.
► The Parkinsonism behaviors were revealed by swing and rotarod tests but not by the apomorphine-induced rotational test.
► Exposure to a natural form of β-carbolines is sufficient for the development of moderate Parkinsonism-like behaviors.