Petri D, de Souza Silva M A, Chao O Y-H, Schnitzler A, Huston J P
Center for Behavioral Neuroscience, Heinrich Heine University Düsseldorf, Universitätsstr. 1, D-40225 Düsseldorf, Germany; Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Düsseldorf, Universitätsstr. 1, D-40225 Düsseldorf, Germany.
Center for Behavioral Neuroscience, Heinrich Heine University Düsseldorf, Universitätsstr. 1, D-40225 Düsseldorf, Germany.
Neuroscience. 2015 Oct 29;307:51-63. doi: 10.1016/j.neuroscience.2015.08.022. Epub 2015 Aug 24.
Parkinson's disease (PD) patients not only exhibit motor impairments, but also characteristic deficits in cognitive and affective functions. Such functions have consistently been associated with the medial prefrontal cortex (mPFC). To determine whether there is an interaction between the midbrain dopamine system (MDS) and the mPFC underlying the cognitive and emotional deficits seen in rats, we administered a disconnection procedure of these structures by applying lesions to the mPFC (N-methyl-d-aspartic acid (NMDA)) and the medial forebrain bundle (6-hydroxydopamine (6-OHDA)) either in the same or opposite hemispheres. The results indicate a functional interaction of the MDS and the mPFC: Disconnection effects on behavior were observed with respect to memory-, anxiety- and depression-related behaviors. A disconnection of the mPFC and MDS had promnestic, antidepressant- and anxiolytic-like effects. In order to determine whether this circuit between the mPFC and MDS involves serotonergic mechanisms, we also utilized serotonin-specific disconnections of the mPFC by applying the 5-HT-specific agent 5,7-dihydroxytryptamine (5,7-DHT) into the mPFC and 6-OHDA into the medial forebrain bundle, again either in the same or opposite hemispheres. The behavioral effects observed here resembled those incurred by the unspecific disconnection of the mPFC, demonstrating a significant contribution of serotonergic mechanisms to the interplay between the MDS and the mPFC. Taken together, these experiments provide evidence for an interaction of the MDS and the mPFC in the control of cognitive and affective processes known to be impaired in PD and point toward a prominent involvement of the serotonergic system. A disconnection of the mPFC and the MDS had promnestic, antidepressant- and anxiolytic-like behavioral effects. These findings may impact therapeutic approaches in the treatment of cognitive and neuropsychiatric symptoms seen in PD.
帕金森病（PD）患者不仅表现出运动障碍，还存在认知和情感功能方面的特征性缺陷。这些功能一直与内侧前额叶皮质（mPFC）相关。为了确定中脑多巴胺系统（MDS）与mPFC之间是否存在相互作用，这种相互作用是大鼠认知和情感缺陷的基础，我们通过在同一或对侧半球对mPFC（N-甲基-D-天冬氨酸（NMDA））和内侧前脑束（6-羟基多巴胺（6-OHDA））进行损伤，实施了这些结构的切断手术。结果表明MDS与mPFC之间存在功能相互作用：在记忆、焦虑和抑郁相关行为方面观察到了对行为的切断效应。mPFC和MDS的切断具有改善记忆、抗抑郁和抗焦虑样作用。为了确定mPFC和MDS之间的这个回路是否涉及5-羟色胺能机制，我们还通过将5-羟色胺特异性药物5,7-二羟基色胺（5,7-DHT）注入mPFC以及将6-OHDA注入内侧前脑束，同样在同一或对侧半球，利用了mPFC的5-羟色胺能特异性切断。此处观察到的行为效应类似于mPFC非特异性切断所产生的效应，表明5-羟色胺能机制对MDS与mPFC之间的相互作用有显著贡献。综上所述，这些实验为MDS与mPFC在控制已知在PD中受损的认知和情感过程中的相互作用提供了证据，并表明5-羟色胺能系统有突出作用。mPFC和MDS的切断具有改善记忆、抗抑郁和抗焦虑样行为效应。这些发现可能会影响PD中所见认知和神经精神症状的治疗方法。
