Integrative Neurophysiology and Neurotechnology, Neuronano Research Center, Department of Experimental Medical Sciences, Lund University, BMC, S-221 84 Lund, Sweden.
Brain Institute, Federal University of Rio Grande do Norte, Av. Nascimento de Castro, 2155, 59056-450 Natal, RN, Brazil.
Exp Neurol. 2018 Apr;302:155-168. doi: 10.1016/j.expneurol.2018.01.010. Epub 2018 Jan 13.
Recently, the biased and highly selective 5-HT agonists, NLX-112, F13714 and F15599, have been shown to alleviate dyskinesia in rodent and primate models of Parkinson's disease, while marginally interfering with antiparkinsonian effects of levodopa. To provide more detailed information on the processes underlying the alleviation of dyskinesia, we have here investigated changes in the spectral contents of local field potentials in cortico-basal ganglia-thalamic circuits following treatment with this novel group of 5-HT agonists or the prototypical agonist, 8-OH-DPAT. Dyskinetic symptoms were consistently associated with 80 Hz oscillations, which were efficaciously suppressed by all 5-HT agonists and reappeared upon co-administration of the antagonist, WAY100635. At the same time, the peak-frequency of fast 130 Hz gamma oscillations and their cross-frequency coupling to low-frequency delta oscillations were modified to a different extent by each of the 5-HT agonists. These findings suggest that the common antidyskinetic effects of these drugs may be chiefly attributable to a reversal of the brain state characterized by 80 Hz gamma oscillations, whereas the differential effects on fast gamma oscillations may reflect differences in pharmacological properties that might be of potential relevance for non-motor symptoms.
最近，具有偏倚性和高度选择性的 5-HT 激动剂 NLX-112、F13714 和 F15599 已被证明可缓解帕金森病啮齿动物和灵长类动物模型中的运动障碍，同时轻微干扰左旋多巴的抗帕金森病效应。为了提供有关运动障碍缓解背后过程的更详细信息，我们在此研究了新型 5-HT 激动剂或原型激动剂 8-OH-DPAT 治疗后皮质基底节丘脑回路局部场电位的光谱含量变化。运动障碍症状与 80 Hz 振荡一致相关，所有 5-HT 激动剂均有效地抑制了这些振荡，而拮抗剂 WAY100635 则重新出现了这些振荡。与此同时，快速 130 Hz 伽马振荡的峰值频率及其与低频 delta 振荡的交叉频率耦合被每种 5-HT 激动剂以不同的程度改变。这些发现表明，这些药物的共同抗运动障碍作用可能主要归因于大脑状态的逆转，该状态的特征是 80 Hz 伽马振荡，而对快速伽马振荡的不同影响可能反映了药理学特性的差异，这些差异可能与非运动症状有关。
