Pharmacologic Interactions between the Muscarinic Cholinergic and Dopaminergic Systems in the Modulation of Prepulse Inhibition in Rats
Pharmacologic Interactions between the Muscarinic Cholinergic and Dopaminergic Systems in the Modulation of Prepulse Inhibition in Rats
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毒蕈碱胆碱能系统和多巴胺能系统在调节大鼠前脉冲抑制中的药理相互作用
DOI：
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发表时间：
2005
影响因子：
3.5
通讯作者：
H. Shannon
中科院分区：
文献类型：
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作者：
Carrie K Jones;E. L. Eberle;David B. Shaw;D. McKinzie;H. Shannon
声惊吓反射的前脉冲抑制（PPI）是一种感觉运动门控过程，已知在许多神经和精神疾病（包括精神分裂症）中存在缺陷。多种证据表明多巴胺能和毒蕈碱胆碱能系统在调节 PPI 中发挥着重要作用。此外，多巴胺能系统和毒蕈碱胆碱能系统之间的相互作用是众所周知的。然而，人们对这两个系统在调节 PPI 方面的潜在相互作用知之甚少。因此，本研究的目的是确定毒蕈碱胆碱能系统和多巴胺能系统在调节 PPI 中是否存在相互作用。在雄性 Sprague-Dawley 大鼠中评估了毒蕈碱胆碱能受体激动剂逆转阿扑吗啡（一种 D1/D2 多巴胺受体激动剂）诱导的 PPI 破坏的功效。 M1/M4 偏好的毒蕈碱激动剂 xanomeline 和 M2/M4 偏好的激动剂 BuTAC [([5R-[exo]-6-[丁硫基]-1,2,5-噻二唑-3-基-]-1-氮杂环环-[3.2.1])辛烷草酸盐]以类似于产生的方式逆转阿扑吗啡诱导的 PPI 破坏由 D2 样多巴胺受体拮抗剂氟哌啶醇和奥氮平组成。毒蕈碱激动剂氧化震颤素、RS86 [[2-乙基-8-甲基-2,8-二氮杂螺(4.5)癸烷-1,3-二酮]盐酸盐]、毛果芸香碱、米拉梅林和沙可美林也可逆转阿朴吗啡诱导的 PPI 破坏。此外，毒蕈碱拮抗剂东莨菪碱也会破坏 PPI，D2 样受体拮抗剂氟哌啶醇（但不是 D1 样受体拮抗剂 SCH23390 [R-(+)-7-氯-8-羟基-3-甲基-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂]）逆转东莨菪碱诱导的破坏。此外，xanomeline 可显着逆转东莨菪碱对 PPI 的破坏。总的来说，目前的研究结果表明，毒蕈碱胆碱能系统和多巴胺能系统在调节 PPI 方面存在功能性相互作用，并且毒蕈碱胆碱能激动剂可能有效治疗 PPI 和精神分裂症中观察到的其他认知障碍。
Prepulse inhibition (PPI) of the acoustic startle reflex is a sensorimotor gating process known to be deficient in a number of neurologic and psychiatric conditions, including schizophrenia. Multiple lines of evidence have indicated that the dopaminergic and muscarinic cholinergic systems play an important role in modulating PPI. Moreover, interactions between the dopaminergic and muscarinic cholinergic systems are well known; however, little is known about potential interactions between the two systems in modulating PPI. Therefore, the purpose of the present studies was to determine whether interactions occur between the muscarinic cholinergic and dopaminergic systems in modulating PPI. The efficacy of muscarinic cholinergic receptor agonists in reversing the disruption of PPI induced by apomorphine, a D1/D2 dopamine receptor agonist, was evaluated in male Sprague-Dawley rats. The M1/M4-preferring muscarinic agonist xanomeline and the M2/M4-preferring agonist BuTAC [([5R-[exo]-6-[butylthio]-1,2,5-thiadiazol-3-yl-]-1-azabyciclo-[3.2.1])octane oxalate] reversed the apomorphine-induced disruption of PPI in a manner similar to that produced by the D2-like dopamine receptor antagonists haloperidol and olanzapine. The muscarinic agonists oxotremorine, RS86 [[2-ethyl-8-methyl-2,8-diazaspiro(4.5)decane-1,3-dione] hydrochloride], pilocarpine, milameline, and sabcomeline also reversed the apomorphine-induced disruption of PPI. Moreover, the muscarinic antagonist scopolamine also disrupted PPI, and the D2-like receptor antagonist haloperidol, but not the D1-like receptor antagonist SCH23390 [R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine], reversed the scopolamine-induced disruption. In addition, xanomeline produced a significant reversal of the disruption in PPI produced by scopolamine. Collectively, the present findings demonstrate that a functional interaction occurs between the muscarinic cholinergic and dopaminergic systems in modulating PPI and that muscarinic cholinergic agonists may be effective in the treatment of the PPI and other cognitive impairments observed in schizophrenia.
影响因子：
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作者：
D. Braff;C. Grillon;M. Geyer
通讯作者：
D. Braff;C. Grillon;M. Geyer
D2 多巴胺受体激动剂会破坏大鼠的感觉运动门控。
DOI：
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发表时间：
1990
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
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作者：
Peng,RY;Mansbach,RS;Braff,DL;Geyer,MA
通讯作者：
Geyer,MA
影响因子：
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作者：
N. Swerdlow;D. Braff;N. Taaid;M. Geyer
通讯作者：
N. Swerdlow;D. Braff;N. Taaid;M. Geyer