Pessiglione Mathias, Guehl Dominique, Jan Caroline, François Chantal, Hirsch Etienne C, Féger Jean, Tremblay Léon
Neurologie et Thérapeutique expérimentale (INSERM U289), Hôpital de la Salpêtrière, Paris, France.
Eur J Neurosci. 2004 Jan;19(2):437-46. doi: 10.1111/j.0953-816x.2003.03089.x.
The motor and cognitive symptoms of Parkinson's disease (PD) are well documented, but little is known about the functionality of motivational processes mediated by the limbic circuits of basal ganglia. The aim of this study was to test the ability of motivational processes to direct and to urge behaviour, in four vervet monkeys (Cercopithecus aethiops) progressively intoxicated with systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injections (0.3-0.4 mg/kg every 4-7 days). In the food preference task, the monkeys had to retrieve two types of directly visible food, simultaneously available in the wells of a reward board. At all stages of MPTP-induced parkinsonism, the monkeys continued to take their favourite food first. In the symbol discrimination task, the wells were covered with sliding plaques cued by symbols indicating the absence or presence of a reward, and the different types of food were blocked in separate sessions. Monkeys with mild or moderate parkinsonism made fewer attempts and took longer to retrieve non-preferred compared with preferred rewards. These results indicate that motivational processes are still able to direct (food preference task) and to urge (symbol discrimination task) behaviour in MPTP-lesioned monkeys. Such a functional preservation may be related to the relatively spared dopaminergic innervation of the limbic circuits that we found in our monkeys, in agreement with the literature on humans. Furthermore, the frequency of executive disorders (such as hesitations and freezing) appeared to be much lower with the preferred rewards. Thus, the preserved motivational processes may help to overcome executive dysfunction in the early stages of human PD.
帕金森病(PD)的运动和认知症状已有充分记录,但对于基底神经节边缘回路介导的动机过程的功能却知之甚少。本研究的目的是测试动机过程引导和促进行为的能力,对四只黑长尾猴(Cercopithecus aethiops)进行全身注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)(每4 - 7天注射0.3 - 0.4mg/kg)使其逐渐中毒。在食物偏好任务中,猴子必须从奖励板的孔中同时获取两种直接可见的食物。在MPTP诱导的帕金森病的各个阶段,猴子仍然首先选择它们最喜欢的食物。在符号辨别任务中,孔上覆盖有滑动板,通过表示有无奖励的符号提示,并且在不同阶段分别放置不同类型的食物。与偏好奖励相比,患有轻度或中度帕金森病的猴子获取非偏好奖励的尝试次数更少,花费的时间更长。这些结果表明,动机过程仍然能够在MPTP损伤的猴子中引导(食物偏好任务)和促进行为(符号辨别任务)。这种功能保留可能与我们在猴子中发现的边缘回路相对保留的多巴胺能神经支配有关,这与关于人类的文献一致。此外,执行障碍(如犹豫和冻结)的频率在偏好奖励时似乎要低得多。因此,保留的动机过程可能有助于克服人类PD早期的执行功能障碍。