Kudryashova I V, Stepanichev M Yu, Gulyaeva N V
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia.
Neurosci Behav Physiol. 2009 Jan;39(1):65-72. doi: 10.1007/s11055-008-9097-z. Epub 2008 Dec 17.
We have previously demonstrated transient increases in caspase-3 activity in the hippocampus of rat pups from age 17 days. We report here our studies on the effects of inhibition of caspase-3 during this period on the acquisition of a two-way avoidance reaction. Rat pups received intracerebroventricular doses of the caspase-3 inhibitor Z-DEVD-FMK On postnatal day 18. Control animals of the same age received the inactive peptide Z-FA-FMK or isotonic saline solution. Inhibition of caspase-3 during the period of its natural activation in the hippocampus during early ontogenesis was found to impair the development of operant behavior in rats. This was apparent as a reduction in the efficiency of learning during acquisition of active avoidance reactions and decreases in the numbers of intersignal reactions. Administration of the inhibitor had no specific action on the types of conditioned reflex activity less associated with operant learning. Thus, there were no differences between the experimental and control groups in the numbers of emotional reactions to the conditioned stimulus. The number of orientational-investigative conditioned reactions also showed no change after administration of Z-DEVD-FMK. On the background of the reduction in the efficiency of the acquisition of the conditioned active avoidance reflex, the number of incomplete acts, in contrast to other types of conditioned reactions, increased significantly after administration of Z-DEVD-FMK, which is evidence for the persistence of the ability to form associative connections between activation of the conditioned signal and the need to move to the other sector. The difficulty in these animals arose at the decision-taking stage on choosing the appropriate form of behavior. Changes in orientational-investigative behavior were not associated with inhibition of caspase-3 during the critical period of development, as the effects of Z-DEVD-FMK and Z-FA-FMK were similar.
我们之前已经证明，从17日龄起，大鼠幼崽海马体中的半胱天冬酶-3活性会出现短暂升高。我们在此报告我们关于在此期间抑制半胱天冬酶-3对双向回避反应习得影响的研究。18日龄的大鼠幼崽接受脑室内注射半胱天冬酶-3抑制剂Z-DEVD-FMK。同年龄的对照动物接受无活性肽Z-FA-FMK或等渗盐溶液。发现在早期个体发育过程中海马体中半胱天冬酶-3自然激活期间对其进行抑制会损害大鼠操作性行为的发展。这表现为在主动回避反应习得过程中学习效率降低以及信号间反应次数减少。给予抑制剂对与操作性学习关联较少的条件反射活动类型没有特异性作用。因此，实验组和对照组对条件刺激的情绪反应次数没有差异。给予Z-DEVD-FMK后，定向探究性条件反应的次数也没有变化。在条件性主动回避反射习得效率降低的背景下，与其他类型的条件反应相比，给予Z-DEVD-FMK后不完全行为的次数显著增加，这证明在条件信号激活与转移到另一区域的需求之间形成关联连接的能力持续存在。这些动物的困难出现在选择适当行为形式的决策阶段。定向探究行为的变化与发育关键期对半胱天冬酶-3的抑制无关，因为Z-DEVD-FMK和Z-FA-FMK的作用相似。
