Bert Bettina, Voigt Jörg-Peter, Kusserow Heike, Theuring Franz, Rex André, Fink Heidrun
Institute of Pharmacology and Toxicology, Freie Universität Berlin, Koserstrasse 20, 14195 Berlin, Germany.
Pharmacol Biochem Behav. 2009 Mar;92(1):76-81. doi: 10.1016/j.pbb.2008.10.014. Epub 2008 Oct 31.
Even though the role of the serotonin1A (5-HT(1A))-receptor for cognitive processes is undisputed, the exact involvement of pre- and postsynaptic sites remains unexplained. Recently, we introduced a mouse line overexpressing the 5-HT(1A)-receptor in the hippocampus and cortex. In this study we investigated in comparison to wild-type mice their cognitive abilities using the Morris water-maze task and inhibitory avoidance test. Acute effects of pre- and posttraining administered 8-OH-DPAT (0.03-0.3 mg/kg i.p.) were examined in the inhibitory avoidance test. Additionally, habituation learning was studied in the hole-board test. Transgenic mice showed no overall learning deficit. Spatial learning and memory revealed in the Morris water-maze task was comparable to wild-type mice, and both genotypes habituated to the hole-board arena in a similar manner. Comparing the performance of both genotypes in the inhibitory avoidance test, cognitive functions of transgenic mice seemed to be slightly impaired. When 8-OH-DPAT was administered pretraining an amnesic effect was produced only in transgenic mice and only at the highest dose (0.3 mg/kg). Posttraining administered 0.3 mg/kg 8-OH-DPAT did not affect the performance of both genotypes. Overall, the cortical and hippocampal overexpression of the 5-HT(1A)-receptor had no major effect on cognitive functions in mice, suggesting that changes in the 5-HT(1A)-receptor density are not necessarily accompanied with alterations of learning and memory processes.
尽管血清素1A(5-HT(1A))受体在认知过程中的作用无可争议,但其突触前和突触后位点的确切参与情况仍未得到解释。最近,我们培育了一种在海马体和皮层中过表达5-HT(1A)受体的小鼠品系。在本研究中,我们使用莫里斯水迷宫任务和抑制性回避试验,与野生型小鼠相比,研究了它们的认知能力。在抑制性回避试验中,检测了训练前和训练后给予8-OH-DPAT(0.03 - 0.3毫克/千克腹腔注射)的急性效应。此外,在洞板试验中研究了习惯化学习。转基因小鼠没有表现出整体学习缺陷。莫里斯水迷宫任务中显示的空间学习和记忆与野生型小鼠相当,并且两种基因型以相似的方式适应洞板实验场。比较两种基因型在抑制性回避试验中的表现,转基因小鼠的认知功能似乎略有受损。当在训练前给予8-OH-DPAT时,仅在转基因小鼠中且仅在最高剂量(0.3毫克/千克)下产生遗忘效应。训练后给予0.3毫克/千克的8-OH-DPAT对两种基因型的表现均无影响。总体而言,5-HT(1A)受体在皮层和海马体中的过表达对小鼠的认知功能没有重大影响,这表明5-HT(1A)受体密度的变化不一定伴随着学习和记忆过程的改变。