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

描述（由申请人提供）：前额叶皮层（PFC）含有丰富的多巴胺（DA）神经支配。大多数的电生理研究，检查DA对内侧PFC（mPFC）在体外的影响已在青春期前大鼠。鉴于它最近已被证明，多巴胺能调节mPFC功能的变化postpubertally，目前需要检查DA功能的PFC在成年动物。中皮层DA系统与药物滥用和精神分裂症有关。通常情况下，增加mPFC锥体神经元的兴奋性已被记录后，重复可卡因管理。然而，这些研究在行为敏化范式中使用了非权变管理。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。精神分裂症患者的药物滥用率高于一般人群。类似地，在患有新生儿腹侧海马损伤的动物（精神分裂症的发育动物模型）中观察到增强的刺激剂自我给药。可卡因自我给药后，这种精神分裂症大鼠模型中皮质DA功能发生了什么变化仍有待确定。这些研究的目的是提供一个工作的基础，检查与精神分裂症药物滥用合并症有关的成年动物中多巴胺能调节mPFC功能的改变。

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.