Department of Pharmacotherapy, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Neurosci Lett. 2012 Aug 30;524(2):133-8. doi: 10.1016/j.neulet.2012.07.022. Epub 2012 Jul 20.
Protein phosphorylation is an important mechanism for the post-translational modulation of N-methyl-d-aspartate (NMDA) receptor functions. In the present study, we investigated the levels of NR2B phosphorylation at Tyr1472 and Ser1303 in the nucleus accumbens, striatum, frontal cortex, and hippocampus of rats that exhibit behavioral sensitization to nicotine. Repeated treatment of rats with nicotine (0.6mg/kg, s.c., for 7 days) produced locomotor sensitization accompanied by increased NR2B phosphorylation at Tyr1472 in the nucleus accumbens and striatum, brain regions involved in behavioral sensitization. In contrast, no changes in NR2B phosphorylation were observed after a single treatment with nicotine in these brain regions. In addition, no changes in NR2B phosphorylation at Ser1303 were observed after repeated treatment with nicotine in any examined brain regions. These results suggest that repeated treatment with nicotine induces NR2B phosphorylation at Tyr1472 in the nucleus accumbens and striatum, which might contribute to the development of synaptic and behavioral plasticity in response to nicotine.
蛋白质磷酸化是 N-甲基-D-天冬氨酸(NMDA)受体功能的一种重要的翻译后调节机制。在本研究中,我们研究了在表现出尼古丁行为敏感的大鼠的伏隔核、纹状体、额叶皮层和海马体中 NR2B 磷酸化在 Tyr1472 和 Ser1303 位点的水平。重复给予大鼠尼古丁(0.6mg/kg,皮下,7 天)会产生运动敏化,伴随着伏隔核和纹状体中 NR2B 在 Tyr1472 位点的磷酸化增加,这些脑区与行为敏化有关。相比之下,在这些脑区单次给予尼古丁后,NR2B 的磷酸化没有变化。此外,在任何检查的脑区中,重复给予尼古丁后,NR2B 在 Ser1303 位点的磷酸化也没有变化。这些结果表明,重复给予尼古丁会导致伏隔核和纹状体中 NR2B 在 Tyr1472 位点的磷酸化,这可能有助于对尼古丁的突触和行为可塑性的发展。