Neuroanatomical sites mediating the motivational effects of opioids as mapped by the conditioned place preference paradigm in rats.
Neuroanatomical sites mediating the motivational effects of opioids as mapped by the conditioned place preference paradigm in rats.
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发表时间：
1993
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通讯作者：
R. Bals-Kubik;A. Ableitner;A. Herz;T. Shippenberg
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作者：
R. Bals-Kubik;A. Ableitner;A. Herz;T. Shippenberg
一个无偏的条件位置偏好范式被用来研究介导阿片受体激动剂增强和厌恶效应的神经解剖学基础。单侧显微注射选择性mu激动剂DAMGO到腹侧被盖区（VTA），中边缘和中皮质多巴胺（DA）系统的起源，导致药物相关部位的剂量依赖性偏好。然而，在VTA DA神经元的末端投射部位、伏隔核和内侧前额叶皮层以及下丘脑外侧注射DAMGO没有效果。相比之下，微注射kappa激动剂u50,488和dynorphin衍生物E-2078进入VTA产生部位厌恶。u50,488和E-2078在伏隔核、内侧前额叶皮层和外侧下丘脑微注射后也观察到位置厌恶。然而，将mu和kappa激动剂显微注射到中纹状体DA系统的起源-黑质或其主要终末区-尾状核-壳核均无效果。放射自显影研究显示，这些物质停留在注射部位周围的限制区域内，证实观察到的影响是在那里介导的。因此，这些数据表明VTA中的A10神经元在调节mu和kappa阿片类药物诱导的动机状态中起重要作用。奖励效应与VTA中mu受体的激活有关，而厌恶效应与VTA及其边缘-皮质末端区kappa受体的激活有关。
An unbiased conditioned place preference paradigm was used to examine the neuroanatomical substrates mediating the reinforcing and aversive effects of mu and kappa opioid agonists. Unilateral microinjection of the selective mu agonist DAMGO into the ventral tegmental area (VTA), the origin of the mesolimbic and mesocortical dopamine (DA) systems, resulted in dose-dependent preferences for the drug-associated place. Intracranial injections of DAMGO into terminal projection sites of VTA DA neurons, the nucleus accumbens and the medial prefrontal cortex, however, as well as into the lateral hypothalamus, were without effect. In contrast, microinjections of the kappa agonist U50,488H and the dynorphin derivative E-2078 into the VTA produced place aversions. Place aversions were also observed after microinjections of U50,488H and E-2078 into the nucleus accumbens, medial prefrontal cortex and lateral hypothalamus. However, microinjections of mu and kappa agonists into either the origin of the mesostriatal DA system, the substantia nigra or into its major terminal field, the nucleus caudatus-putamen, was without effect. Autoradiographic studies revealed that the substances remained within a restricted area around the injection site, confirming that the effects observed were mediated therein. Thus, these data suggest an important role for the A10 neurons in the VTA in the regulation of both mu and kappa opioid-induced motivational states. The rewarding effects are associated with the activation of mu receptors in the VTA, whereas aversive effects are associated with the activation of kappa receptors in the VTA and its limbic-cortical terminal regions.