PROMOTER CHARACTERIZATION OF THE CART GENE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这是我们实验室的主要研究项目，其中CART基因表达的调控一直是重点。由于CREB在N-ACC中的过度表达降低了可卡因的奖赏，又因为在N-ACC中注射CART多肽降低了可卡因的奖赏，我们推测在N-ACC中CREB的过表达应该会增加CART的表达，并发现CREB是CART表达的体内调节因子，这似乎是可卡因作用的机制之一。CART肽起到体内平衡调节剂的作用，并倾向于对抗可卡因在伏隔核的作用。 其他几项研究表明：注射可卡因激活了N-ACC中的CART神经元，这有力地支持了早先的一种说法，CART对骨小梁而不是皮质骨量以及骨髓中脂肪细胞的密度有作用，雌激素和孕激素可以影响猕猴中脑中CART的水平。这些后面的研究继续表明CART广泛参与各种生理功能。

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. This is the main research project in our laboratory where regulation of CART gene expression has been a focus. Because over expression of CREB in the N Acc reduces cocaine reward, and because injection of CART peptide into the N Acc reduces cocaine reward, we hypothesized that over expression of CREB in the N Acc should increase expression of CART peptide and found that CREB is an in vivo regulator of CART expression which appears to be a mechanism of the action of cocaine. CART peptide acts as a homeostatic regulator and tends to oppose the action of cocaine in the nucleus accumbens. Several other studies have shown: that administration of cocaine activates CART neurons in the N Acc  which supports strongly an earlier proposal, that CART has a role in trabecular but not cortical bone mass as well as in the density of fat cells in bone marrow, and that estrogen and progesterone can affect CART levels in the midbrain in macaques. These latter studies continue to show the broad involvement of CART in a variety of physiological functions.