Izquierdo L A, Viola H, Barros D M, Alonso M, Vianna M R, Furman M, Levi de Stein M, Szapiro G, Rodrigues C, Choi H, Medina J H, Izquierdo I
Centro de Memoria, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcellos 2600 (90035-003) Porto Alegre, RS, Brazil.
Eur J Neurosci. 2001 Apr;13(7):1464-7. doi: 10.1046/j.0953-816x.2001.01530.x.
Rats exposed to a novel environment just prior to or 1-2 h, but not 4 or 6 h, before retention testing exhibited an enhanced retrieval of a one-trial inhibitory avoidance training. The bilateral intrahippocampal infusion of PD098059, an inhibitor of mitogen-activated protein kinase (MAPK), the specific upstream activator of p42 and p44 MAPKs, given 10 min before the exposure to the novel environment, blocked the enhancing effect of novelty on memory retrieval. In addition, prenovelty infusion of DL-2-amino-5-phosphonovalerate (APV), an antagonist of glutamate NMDA receptors, produced similar effects. The exposure to the novel environment is associated with an activation of p42 and p44 MAPKs and an increase in the phosphorylation state of the transcription factor cAMP response element binding protein (CREB). No changes were observed in cAMP-dependent protein kinase (PKA) activity or in alpha-CAMKII activation. Taken together, our results indicate that novelty activates hippocampal MAPKs, which are necessary, along with glutamate NMDA receptors, for the enhancing effect of novelty on retrieval.
在记忆保持测试前即刻或提前1-2小时而非4或6小时暴露于新环境的大鼠，表现出一次性抑制性回避训练的记忆提取增强。在暴露于新环境前10分钟双侧海马内注射丝裂原活化蛋白激酶（MAPK）的抑制剂PD098059（p42和p44 MAPKs的特异性上游激活剂），可阻断新环境对记忆提取的增强作用。此外，在新环境暴露前注射谷氨酸NMDA受体拮抗剂DL-2-氨基-5-磷酸戊酸（APV）也产生了类似的效果。暴露于新环境与p42和p44 MAPKs的激活以及转录因子环磷酸腺苷反应元件结合蛋白（CREB）磷酸化状态的增加有关。在环磷酸腺苷依赖性蛋白激酶（PKA）活性或α-钙调蛋白激酶II（α-CAMKII）激活方面未观察到变化。综上所述，我们的结果表明，新环境激活海马MAPKs，其与谷氨酸NMDA受体一起，对于新环境对记忆提取的增强作用是必需的。
