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Unilateral lesions of the Nigrostriatal pathway

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  1. Abstract.
  2. Introduction.
  3. Materials and methods.
    1. Animals.
    2. Surgery.
  4. Behavioral testing.
    1. Preoperative testing.
    2. Postoperative testing.
  5. Histology.
    1. Intracardial perfusion.
    2. Sectioning and staining.
    3. Anatomical analysis.
  6. Statistical analysis.
    1. Behavioral analysis.
    2. Anatomical analysis.
  7. Pargyline versus no Pargyline-injected group.
  8. Correlation between percentage of cell loss and rotational behavior.
  9. Discussion.
  10. Role of lesion size.
  11. Conclusion.

The nigrostriatal system through the basal ganglia is essential for regulating motor movement. Normal motor behavior requires a delicate balance between the excitatory direct pathway and the inhibitory indirect pathway modulated by the D1 and D2 receptors, respectively. Unilateral destruction of the striatum or its dopaminergic inputs changes unidirectional behavior in animals. The most common method of inducing a unilateral lesion is through the injection of the neurotoxin 6-OHDA in substantia nigra pars compacta (SNc). This lesion causes a lateralized destruction of dopamine neurons as well as a loss of striatal dopamine innervation. The anatomical and behavioral effects of amphetamine and apomorphine were examined to investigate the role of dopamine neurons in the nigrostriatal pathway. Amphetamine induced net ipsiversive rotations while apomorphine induced net contraversive rotation with increasing time after 6-OHDA lesions. The role of lesion size has contributed substantially to the rotational behavior of both drugs. Furthermore, behavioral effects of this lesion are similar to motor symptoms and neuropathology seen in patients with Parkinson's Disease. Hence, the 6-OHDA lesion may be a relevant model for finding the treatment of Parkinson's disease.

[...] In experimental animals, the total number of rotations was five times greater post-amphetamine injection than pre-injection 4.049 Similarly, in control rats the total number of rotations was three times greater post-amphetamine injection than pre-injection 2.530 After establishing the baseline response to amphetamine, experimental rats with unilateral 6-OHDA lesions developed significant ipsilateral rotation bias 6-7 days as well as 10-11 days post-surgery following amphetamine injection, while the control group showed no variation in net ipsiversive rotations pre- and post-operatively (Figure 5). [...]


[...] Furthermore, studies have shown that a unilateral lesion of the nigrostriatal pathway induces postural asymmetry (Ungerstedt, 1971). The role of dopamine neurons and the effect of 6-OHDA lesions in SNc have been investigated with respect to rotational behavior under amphetamine and apomorphine. The effect of these drugs, however, varied depending on the placement and the extent of the lesion produced. Results from other studies have suggested that 6-OHDA injected into the SN pars compacta can effectively induce lesions to DA neurons (Fornaguera et al., 1994). [...]


[...] We first determined the dominant hemisphere of the nigrostriatal pathway, and then produced a unilateral 6-OHDA lesion in SNc of the dominant hemisphere. Then, we sought to examine the effects of disruption of the motor pathway by observing differences in rotational behavior with the injection of amphetamine and apomorphine. Lastly, we evaluated the role of lesion degree and tried to correlate that to the disrupted rotational behavior. We hypothesized that when of neuronal cell loss was observed, amphetamine would induce ipsiversive rotational behavior and that apomorphine would induce contraversive rotational behavior in a unilateral 6-OHDA lesion with increasing time after lesion. [...]

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