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

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。大多数体外电生理研究检测DA对内侧PFC （mPFC）的影响，这些研究都是在青春期前的大鼠身上进行的。鉴于最近有研究表明，多巴胺能调节的前皮层皮层功能在青春期后发生变化，目前有必要研究成年动物前皮层的DA功能。中皮质DA系统与药物滥用和精神分裂症有关。通常，在反复服用可卡因后，mPFC锥体神经元的兴奋性增加已被证明。然而，这些研究在行为致敏范式中使用了非偶然给药。因此，将对可卡因自我服用后PFC兴奋性的变化进行研究，这是一种更类似于人类使用的药物滥用行为模型。精神分裂症患者的药物滥用率高于一般人群。同样，在患有新生儿海马腹侧病变（一种发育性精神分裂症动物模型）的动物中也观察到兴奋剂自我给药增强。在这种精神分裂症大鼠模型中，可卡因自我给药后皮质DA功能发生了什么变化仍有待确定。这些研究的目的是为研究与精神分裂症-药物滥用合并症相关的成年动物mPFC功能多巴胺能调节的改变提供基础。

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.