Yamazaki Yoshihiko, Jia Yousheng, Niu Rong, Sumikawa Katumi
Department of Neurobiology and Behavior, University of California Irvine, CA 92697-4550, USA.
Eur J Neurosci. 2006 Apr;23(7):1819-28. doi: 10.1111/j.1460-9568.2006.04714.x.
The use of nicotine via cigarette smoking forms long-lasting memories that are recalled in response to environmental cues associated with previous nicotine use. However, the changes in brain memory systems that underlie these long-lasting memories are not well understood. The N-methyl-D-aspartate receptor (NMDAR) is critical for long-lasting modifications of synapses. Here we show that in vivo nicotine exposure induces the enhancement of NR2B-containing NMDAR-mediated currents in the hippocampus, a brain region associated with the formation of memories. This nicotine effect is maintained during continued nicotine exposure and is accompanied by increased tyrosine phosphorylation of NR2B. Furthermore, long-term potentiation (LTP), which is considered to be a cellular substrate of learning and memory, induced in nicotine-exposed hippocampi contains a protein synthesis-independent long-lasting component. An NR2B-selective antagonist blocks a long-lasting component of LTP, but not LTP. These results suggest that exposure to nicotine provides conditions that promote the induction of long-lasting modifications of synapses, which may be involved in the formation of memories involving nicotine use.
通过吸烟使用尼古丁会形成持久的记忆，这些记忆会在与先前使用尼古丁相关的环境线索的刺激下被唤起。然而，构成这些持久记忆基础的大脑记忆系统的变化尚未得到充分理解。N-甲基-D-天冬氨酸受体（NMDAR）对于突触的持久修饰至关重要。在此我们表明，体内尼古丁暴露会诱导海马体中含NR2B的NMDAR介导电流增强，海马体是一个与记忆形成相关的脑区。这种尼古丁效应在持续的尼古丁暴露过程中得以维持，并伴随着NR2B酪氨酸磷酸化的增加。此外，在尼古丁暴露的海马体中诱导的长时程增强（LTP），被认为是学习和记忆的细胞基础，包含一个不依赖蛋白质合成的持久成分。一种NR2B选择性拮抗剂可阻断LTP的持久成分，但不能阻断LTP。这些结果表明，尼古丁暴露提供了促进突触持久修饰诱导的条件，这可能参与了与尼古丁使用相关的记忆形成。
