Anan Madoka, Higa Ryoko, Shikano Kenshiro, Shide Masahito, Soda Akinobu, Carrasco Apolinario Magdeline E, Mori Kenji, Shin Toshitaka, Miyazato Mikiya, Mimata Hiromitsu, Hikida Takatoshi, Hanada Toshikatsu, Nakao Kazuwa, Kangawa Kenji, Hanada Reiko
Department of Neurophysiology, Faculty of Medicine, Oita University, Oita, Japan.
Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
Heliyon. 2020 May 19;6(5):e03947. doi: 10.1016/j.heliyon.2020.e03947. eCollection 2020 May.
Neuromedin U (NMU) is a bioactive neuropeptide, highly distributed in the gastrointestinal tract and the central nervous system. NMU has various physiological functions related to feeding behavior, energy metabolism, stress responses, circadian rhythmicity and inflammation. Recently, several reports indicate that the central NMU system plays an important role in the reward systems in the brain. However, the underlying molecular mechanisms are not yet fully defined. In this study, we found that some of cocaine-induced c-Fos immunoreactive cells were co-localized with NMU in the nucleus accumbens (NAc), caudate putamen (CPu), and basolateral amygdala (BLA), which are key brain regions associated with the brain reward system, in wild type mice. Whereas, a treatment with cocaine did not influence the kinetics of NMU or NMU receptors mRNA expression in these brain regions, and NMU-knockout mice did not show any higher preference for cocaine compared with their control mice. These results indicate that cocaine has some effect on NMU expressing neurons related to the brain reward system, and this suggests NMU system may have a role on the brain reward systems activated by cocaine.
神经介素U(NMU)是一种生物活性神经肽,在胃肠道和中枢神经系统中高度分布。NMU具有与进食行为、能量代谢、应激反应、昼夜节律和炎症相关的多种生理功能。最近,一些报告表明,中枢NMU系统在大脑的奖赏系统中起重要作用。然而,其潜在的分子机制尚未完全明确。在本研究中,我们发现野生型小鼠中,一些可卡因诱导的c-Fos免疫反应性细胞在伏隔核(NAc)、尾壳核(CPu)和基底外侧杏仁核(BLA)中与NMU共定位,这些都是与大脑奖赏系统相关的关键脑区。然而,可卡因处理并未影响这些脑区中NMU或NMU受体mRNA表达的动力学,并且与对照小鼠相比,NMU基因敲除小鼠对可卡因没有表现出更高的偏好。这些结果表明,可卡因对与大脑奖赏系统相关的NMU表达神经元有一定影响,这表明NMU系统可能在由可卡因激活的大脑奖赏系统中起作用。