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 (4μl) of NH
solution at 2 or 200ng/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.