Hyperactivity response to apomorphine and amphetamine in the mouse: the importance of the nucleus accumbens and caudate‐putamen
Hyperactivity response to apomorphine and amphetamine in the mouse: the importance of the nucleus accumbens and caudate‐putamen
复制标题
小鼠对阿扑吗啡和安非他明的过度活跃反应：伏隔核和尾壳核的重要性
DOI：
10.1111/j.2042-7158.1979.tb13494.x
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发表时间：
1979
影响因子：
3.3
通讯作者：
V. Nohria
中科院分区：
文献类型：
--
作者：
Brenda Costaix;R. Naylor;V. Nohria
使用正常动物的运动过度反应（例如在光电池笼或活动轮中测量的那些）作为精神安定剂的特定运动抑制作用的测试的缺点是它们通常无法检测非典型精神安定剂，例如舒必利。因此，人们的兴趣集中在小鼠对阿朴吗啡的过度活跃反应上，该反应将检测舒必利和类似药物，并允许通过简单的药物相互作用消除非精神安定药物，如甲氧氯普胺（protais 等人，1976 年；Costall 等人，1978 年）。在已知对运动控制很重要的两个大脑区域中，伏隔核和纹状体（参见 Costall & Naylor 1977 年的综述），脑损伤研究表明，纹状体而不是伏隔核是阿朴吗啡可诱发多动反应的部位，这种反应已被量化为攀爬行为（Protais 等人 1976 年）。然而，很难将这一发现与“检测”舒必利和其他非典型药物作用的攀爬行为的新颖性相协调，因为中脑边缘区域（例如伏核）的变化现在被认为至少与纹状体功能的变化对精神安定作用的影响一样重要（Costall＆Naylor 1976; Waldmeier＆Maitre 1976; Elliott et a1 1977）。对转圈行为的研究证明了这一点，转圈行为可以通过精神安定剂调节，表明虽然纹状体损伤可能导致不对称，但伏隔核可以提供运动驱动的组成部分（Pycock & Marsden 1978）。因此，本研究旨在重新评估伏隔核和纹状体对于诱导阿扑吗啡诱导的小鼠攀爬行为的重要性。与安非他明诱导的多动症进行了比较，因为阿扑吗啡未能在所用小鼠品系中诱导以攀爬以外的形式表达的运动多动症。选择安非他明也是因为它能够通过中脑边缘区域引起过度活跃（Costall & Naylor 1977）。研究使用雄性白化小鼠，BKW 品系，实验开始时 25-30 g，手术时 35-40 g。使用为大鼠提供的Kopf立体定位仪和杆和切牙杆(升高到耳间线上方2.0mm)进行立体定位手术。用水合氯醛（450 mg kg-* ip）麻醉小鼠，并使用不锈钢电极（直径 0.65 mm）在尾壳核中诱导电损伤，除尖端外均绝缘，并通过 1.5 mA 电流*对应。
A disadvantage to the use of locomotor hyperactivity responses in normal animals (such as those measured in photocell cages or in activity wheels) as tests for the specific locomotor depressant actions of neuroleptic agents is their general failure to detect atypical neuroleptics such as sulpiride. Interest has, therefore, focused on a hyperactivity response in the mouse to apomorphine which will detect sulpiride and similar agents and allow the elimination of non-neuroleptic agents such as metoclopramide by simple drug interactions (protais et al 1976; Costall et a1 1978). Of two brain regions known to be important for motor control, the nucleus accumbens and striatum (see review by Costall & Naylor 1977), the striatum, rather than the nucleus accumbens, has been indicated by brain lesion studies to be the site at which apomorphine can induce the hyperactivity response, which has been quantified as a climbing behaviour (Protais et a1 1976). However, it is difficult to reconcile this finding with the novelty of climbing behaviour to ‘detect’the actions of sulpiride and other atypical agents since changes in the mesolimbic regions such as the nucleus accumbens are now considered to be at least as important as changes in striatal function for the neuroleptic effect (Costall & Naylor 1976; Waldmeier & Maitre 1976; Elliott et a1 1977). This has been exemplified by studies on circling behaviour, which can be modulated by neuroleptic agents, showing that whilst striatal damage may cause asymmetry, it is the nucleus accumbens which can provide a component of motor drive (Pycock & Marsden 1978). Therefore, the present studies were designed to re-evaluate the importance of the nucleus accumbens and striatum for the induction of climbing behaviour induced by apomorphine in the mouse. Comparisons were made with amphetamine-induced hyperactivity since apomorphine failed to induce a locomotor hyperactivity, expressed in a form other than climbing, in the strain of mouse used. Amphetamine was also selected on the basis of its ability to cause hyperactivity via the mesolimbic areas (Costall & Naylor 1977).The studies used male albino mice, BKW strain, 25-30 g at the beginning of an experiment or 35-40 g at the time of operation. Stereotaxic surgery was carried out using a Kopf stereotaxic instrument and bars and incisor bar (raised 2.0 mm above the inter-aural line) supplied for the rat. Mice were anaesthetized with chloral hydrate, 450 mg kg-* ip, and eletrolesions were induced in the caudate-putamen using a stainless steel electrode (0.65 mm diam.) Insulated except at the tip, and passing 1.5 mA for* Correspondence.