DOPAMINE MODULATION OF LIMBIC CORTICO ACCUMBENS SYSTEM

边缘皮质伏隔系统的多巴胺调节

• 批准号: 6655545
• 负责人: Shao-Pii Onn
• 金额: $ 19万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-09 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6655545
• 关键词: amphetamines; chemical stimulation; dopamine; dopamine receptor; drug addiction; electrophysiology; evoked potentials; immunocytochemistry; immunofluorescence technique; laboratory rat; limbic system; microelectrodes; neural transmission; neurons; neurophysiology; neuroregulation; nucleus accumbens; organ culture; prefrontal lobe /cortex; synapses

DESCRIPTION: (Adapted from the Investigator's Abstract) Psychostimulant abuse in humans is known to produce states similar to both positive and negative symptoms of schizophrenia. Studies in rats have suggested that hyper-dopaminergic activity in subcortical structures such as nucleus accumbens leads to behavioral abnormality that may have relevance to positive symptoms. Emotional and cognitive deficits that characterize negative symptoms have been recently demonstrated in monkeys similarly treated with low doses of amphetamine and that in many ways resemble those identified in human amphetamine abusers. These cognitive deficits are believed to result from a dysfunction in the prefrontal cortex, thus linking to a clinical state of hypofrontality. A basic dysfunction of prefrontal-accumbens circuits is thought to be critical to the cognitive dysfunction, negative affect and abnormal reward-related behavior that is characteristic of schizophrenia and drug abuse. My working hypotheses is that in amphetamine treated rats there exists deficits in the excitatory drive from the limbic afferents from the entorhinal cortex and the mediodorsal thalamus to the prefrontal cortex and/or deficits in the dopamine modulation of these excitatory afferents. Thus the proposed experiments using in vivo intracellular recording and labeling techniques will compare and contrast information arising intracortically (eg entorhinal cortex; aim 1) and subcortically (eg mediodorsal thalamus; aim 2), the latter of which transmits basal ganglia outflow back to the prefrontal cortex. Lastly cortical processing in influencing basal ganglia outflow from the nucleus accumbens. I predict attenuated intracortical processing (aim 1) to occur in conjunction with an augmented basal ganglia feedback circuit, as marked by increases in both mediodorsal thalamus-evoked activity in prefrontal cortex neurons (aim 2) and prefrontal cortex-evoked activity in nucleus accumbens neurons (aim 3), in amphetamine treated rats. The proposed study is of particular interest with respect to the deficit syndrome in schizophrenia and possibly other mental disorders such as drug addiction associated with negative affect and depression.

描述：（改编自研究者摘要）精神兴奋剂滥用 在人类中产生类似于积极和消极的状态 精神分裂症的症状。对老鼠的研究表明， 皮质下结构如丘脑核中的高多巴胺能活性 导致可能与阳性症状相关的行为异常。 以阴性症状为特征的情感和认知缺陷一直是 最近在用低剂量的 安非他明，并且在许多方面类似于在人类中鉴定的那些 安非他明滥用者这些认知缺陷被认为是由于 前额叶皮层功能障碍，因此与临床状态有关， 前额叶功能减退一个基本的功能障碍，前额叶-脑桥电路被认为是 对认知功能障碍、负性情绪和异常 精神分裂症和药物滥用所特有的奖励相关行为。 我的工作假设是，在安非他明治疗的大鼠存在缺陷， 来自内嗅皮层的边缘传入神经的兴奋性驱动 和中背丘脑到前额叶皮层和/或 多巴胺对这些兴奋性传入神经的调节。因此，建议 使用体内细胞内记录和标记技术的实验将 比较和对比皮质内产生的信息（如内嗅皮质; aim 1）和皮质下（如内侧背丘脑; aim 2），后者， 将基底神经节的流出物传输回前额皮质。最后皮质 影响基底神经节流出脑桥核的加工。我 预测皮质内处理（aim 1）减弱与 随着基底神经节反馈回路的增加， 双侧中背丘脑诱发的前额叶皮层神经元活动（aim 2） 和前额叶皮层诱发的活动，在延髓核神经元（aim 3）， 安非他明处理的大鼠。拟议的研究特别令人感兴趣， 关于精神分裂症和其他精神疾病的缺陷综合征， 与负面影响有关的药物成瘾等疾病， 萧条