CART: A NOVEL COCAINE REGULATED NEUROCHEMICAL

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。在过去的一年里取得了非常实质性的进展。主要的发现是通过信号和结合在AtT20细胞中鉴定出CART受体。这一进展将允许在受体上筛选潜在的药物，并为克隆受体提供工具。此外，我们提供了CART至少部分受皮质酮调节的证据，这可能有助于解释文献中的一些观察结果。CART在大脑和血清中也表现出昼夜节律。正如预期的那样，CART基因敲除小鼠有各种行为变化，这支持了许多论文，表明CART在许多生理过程中发挥着重要作用。我们还发现了一条可能是一条重要的神经通路，即从下丘脑外侧到VTA的一条包含CART的通路；这可能是摄食和奖励之间的联系，并部分解释了药物奖励和摄食奖励之间的重叠。许多新的实验现在是可能的，特别是在受体研究领域。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Very substantial progress has been made over the past year. The major finding has been the identification of a CART receptor in AtT20 cells by signaling and binding. This advance will allow screening of potential medications at the receptor and provide tools for cloning the receptor. In addition, we provided evidence that CART is at least partly regulated by corticosterone, which may help explain some observations in the literature. CART also exhibits a diurnal rhythm in brain and serum. As would be expected, CART knockout mice have a variety of behavioral changes which supports many papers indicating an important role for CART in many physiological processes. We also found what may be an important neuronal pathway, a CART-containing pathway from the lateral hypothalamus to the VTA; this may be a connection between feeding and reward and partly explain the overlap between drug reward and feeding reward. Many new experiments are now possible, particularly in the are of receptor studies.