Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, UFPR, C.P. 19.031, 81531-980 Curitiba, PR, Brazil.
Behav Brain Res. 2010 Dec 20;215(1):63-70. doi: 10.1016/j.bbr.2010.06.028. Epub 2010 Jul 1.
Motor impairments of Parkinson's disease (PD) appear only after the loss of more than 70% of the DAergic neurons of the substantia nigra pars compacta (SNc). An earlier phase of this disease can be modeled in rats that received a unilateral infusion of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) into the SNc. Though these animals do not present gross motor impairments, they rotate towards the lesioned side when challenged with DAergic drugs, like amphetamine and apomorphine. The present study aimed to test whether these effects occur because the drugs disrupt compensatory mechanisms that keep extracellular levels of dopamine in the striatum (DA(E)) unchanged. This hypothesis was tested by an in vivo microdialysis study in awake rats with two probes implanted in the right and left striatum. Undrugged rats did not present turning behaviour and their basal DA(E) did not differ between the lesioned and sham-lesioned sides. However, after apomorphine treatment, DA(E) decreased in both sides, but to a larger extent in the lesioned side at the time the animals started ipsiversive turning behaviour. After amphetamine challenge, DA(E) increased in both sides, becoming significantly higher in the non-lesioned side at the time the animals started ipsiversive turning behaviour. These results are in agreement with the hypothesis that absence of gross motor impairments in this rat model of early phase PD depends on maintenance of extracellular DA by mechanisms that may be disrupted by events demanding its alteration to higher or lower levels.
帕金森病（PD）的运动障碍仅在黑质致密部（SNc）中超过 70%的 DA 能神经元丧失后才会出现。该疾病的早期阶段可以在接受神经毒素 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）单侧注入 SNc 的大鼠中建模。尽管这些动物没有明显的运动障碍，但当受到 DA 能药物（如安非他命和阿扑吗啡）的挑战时，它们会向病变侧旋转。本研究旨在测试这些影响是否是因为药物破坏了使纹状体（DA(E)）中外源多巴胺水平保持不变的代偿机制。该假设通过在清醒大鼠中进行的两项探针植入右侧和左侧纹状体的体内微透析研究进行了测试。未用药物处理的大鼠没有出现转向行为，其基础 DA(E)在病变侧和假手术侧之间没有差异。然而，在阿扑吗啡治疗后，两侧的 DA(E)都减少了，但在动物开始向病变侧转向行为时，病变侧减少的程度更大。在安非他命挑战后，两侧的 DA(E)都增加了，但在动物开始向病变侧转向行为时，非病变侧的增加更为显著。这些结果与假设一致，即在这种早期 PD 大鼠模型中没有明显的运动障碍，这取决于通过可能因需要其改变为更高或更低水平而被破坏的机制来维持细胞外 DA。
