Yoo Ji-Hoon, Cho Jae-Han, Lee Seok-Yong, Lee Sanggeol, Loh Horace H, Ho Ing K, Jang Choon-Gon
Department of Pharmacology, College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
Neurosci Lett. 2006 Mar 6;395(2):98-102. doi: 10.1016/j.neulet.2005.10.089. Epub 2005 Nov 21.
This study investigated the expression of nNOS after repeated morphine or cocaine administration in order to determine if nNOS (neuronal nitric oxide synthase) is involved in the morphine- or cocaine-induced behavioral sensitization in mu-opioid receptor knockout (MOR(-/-)) mice. Higher numbers of nNOS-positive cells were observed in the dentate gyrus of the hippocampus (DG) of the wild-type (MOR(+/+)) mice repeatedly treated with either morphine or cocaine than in the saline treated MOR(+/+) mice (morphine, +122%; cocaine, +82%). Moreover, the MOR(-/-) mice also showed significantly higher morphine- or cocaine-induced nNOS expression levels in the DG than in the saline treated MOR(+/+) mice (morphine, +234%; cocaine, +54%). The MOR(-/-) mice showed a significantly higher morphine-induced nNOS expression level (+103%) or a lower cocaine-induced nNOS expression level (+38%) in the DG than in the morphine- or cocaine-treated MOR(+/+) mice. These results suggest that morphine and cocaine sensitization is differentially regulated by the mu-opioid receptors in MOR(-/-) mice via the nNOS systems in the DG.
本研究调查了反复给予吗啡或可卡因后nNOS（神经元型一氧化氮合酶）的表达，以确定nNOS是否参与μ-阿片受体基因敲除（MOR(-/-)）小鼠的吗啡或可卡因诱导的行为敏化。在反复给予吗啡或可卡因的野生型（MOR(+/+)）小鼠海马齿状回（DG）中观察到的nNOS阳性细胞数量，高于给予生理盐水的MOR(+/+)小鼠（吗啡组，增加122%；可卡因组，增加82%）。此外，MOR(-/-)小鼠在DG中由吗啡或可卡因诱导的nNOS表达水平也显著高于给予生理盐水的MOR(+/+)小鼠（吗啡组，增加234%；可卡因组，增加54%）。与给予吗啡或可卡因的MOR(+/+)小鼠相比，MOR(-/-)小鼠在DG中由吗啡诱导的nNOS表达水平显著更高（增加103%），而由可卡因诱导的nNOS表达水平更低（增加38%）。这些结果表明在MOR(-/-)小鼠中，吗啡和可卡因敏化通过DG中的nNOS系统受μ-阿片受体的差异调节。
