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Dopamine Effects in Prefrontal Cortex in Models of Drug Abuse and Schizophrenia

药物滥用和精神分裂症模型中前额皮质的多巴胺作用

基本信息

批准号：
7405847
负责人：
CARRIE E. JOHN
金额：
$ 4.96万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-06-01 至 2010-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7405847
关键词：
Action Potentials Adolescence Adolescent Adult Animal Model Animals Apomorphine Behavior Behavioral Brain Catheters Cells Characteristics Cocaine Comorbidity Condition Control Groups Development Dopamine Dopamine Agonists Dopamine D2 Receptor Dopamine Receptor Drug abuse Drug usage Foundations Goals Hippocampus (Brain)Human In Vitro Interneurons Lesion Measures Medial Membrane Membrane Potentials Modeling Monitor Neonatal Neurobiology Neurons Numbers Operative Surgical Procedures Patients Pharmaceutical Preparations Physiologic pulse Plastics Population Prefrontal Cortex Process Property Pulse taking Rate Rattus Receptor Signaling Regulation Reinforcement Schedule Relative (related person)Resistance Rest Schizophrenia Self Administration Self-Administered Slice Substance abuse problem Sucrose Testing Time Week Withdrawal Work base behavioral sensitization day dopamine system hippocampal pyramidal neuron mature animal nerve supply neuronal excitability patch clamp postnatal psychostimulant research study response

项目摘要

DESCRIPTION (provided by applicant): The prefrontal cortex (PFC) contains a rich dopamine (DA) innervation. The majority of electrophysiological studies examining DA effects on the medial PFC (mPFC) in vitro have been performed in pre-adolescent rats. Given that it has recently been shown that dopaminergic regulation of mPFC function changes postpubertally, there is a present need to examine DA function in the PFC in adult animals. The mesocortical DA system is implicated in drug abuse and schizophrenia. Typically, increased excitability of mPFC pyramidal neurons has been documented after repeated cocaine administration. However, these studies used non-contingent administration in behavioral sensitization paradigms. Therefore, changes in PFC excitability after cocaine self-administration, a model of drug abuse behavior that better resembles human use, will be examined. Schizophrenia patients have been shown to have higher rates of substance abuse than the average population. Similarly, enhanced stimulant self-administration has been observed in animals with a neonatal ventral hippocampal lesion, a developmental animal model of schizophrenia. It remains to be determined what changes occur in cortical DA function in this rat model of schizophrenia after cocaine self-administration. The goal of these studies is to provide a foundation of work examining alterations in dopaminergic regulation of mPFC function in adult animals as related to schizophrenia-drug abuse comorbidity.

描述（由申请人提供）：前额皮质（PFC）含有丰富的多巴胺（DA）神经支配。大多数在体外检查 DA 对内侧 PFC (mPFC) 影响的电生理学研究都是在青春期前的大鼠中进行的。鉴于最近已表明 mPFC 功能的多巴胺能调节在青春期后发生变化，因此目前需要检查成年动物 PFC 中的 DA 功能。中皮质 DA 系统与药物滥用和精神分裂症有关。通常，重复给予可卡因后，mPFC 锥体神经元的兴奋性增加。然而，这些研究在行为敏化范式中使用了非偶然给药。因此，将检查可卡因自我给药后 PFC 兴奋性的变化，这是一种更类似于人类使用的药物滥用行为模型。研究表明，精神分裂症患者的药物滥用率高于普通人群。同样，在患有新生儿腹侧海马病变的动物（一种精神分裂症的发育动物模型）中观察到兴奋剂的自我给药增强。在这种精神分裂症大鼠模型中自我给予可卡因后，皮质 DA 功能发生了什么变化仍有待确定。这些研究的目的是为检查成年动物 mPFC 功能的多巴胺能调节变化与精神分裂症药物滥用共病相关的工作奠定基础。