Camats-Perna Judith, Kalaba Predrag, Ebner Karl, Sartori Simone B, Vuyyuru Harish, Aher Nilima Y, Dragačević Vladimir, Singewald Nicolas, Engelmann Mario, Lubec Gert
AG Neuroendokrinologie und Verhalten, Institut für Biochemie und Zellbiologie, Otto-von-Guericke-Universität Magdeburg, Magdeburg, Germany.
Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Vienna, Austria.
Front Behav Neurosci. 2019 Apr 11;13:63. doi: 10.3389/fnbeh.2019.00063. eCollection 2019.
In the laboratory, long-term social recognition memory (SRM) in mice is highly susceptible to proactive and retroactive interference. Here, we investigate the ability of novel designed dopamine (DA) re-uptake inhibitors (-CE-123 and -CE-123) to block retroactive and proactive interference, respectively. Our data show that administration of -CE-123 30 min before learning blocks retroactive interference that has been experimentally induced at 3 h, but not at 6 h, post-learning. In contrast, treatment 30 min before learning blocked the induction of retroactive interference at 6 h, but not 3 h, post-learning. Administration of -CE-123 failed to interfere with proactive interference at both 3 h and 6 h. Analysis of additional behavioral parameters collected during the memory task implies that the effects of the new DA re-uptake inhibitors on retroactive and proactive interference cannot easily be explained by non-specific effects on the animals' general social behavior. Furthermore, we assessed the mechanisms of action of drugs using intracerebral -microdialysis technique. The results revealed that administration of -CE-123 and -CE-123 dose-dependently increased DA release within the nucleus accumbens of freely behaving mice. Thus, the data from the present study suggests that the DA re-uptake inhibitors tested protect the consolidation of long-term social memory against interference for defined durations after learning. In addition, the data implies that DA signaling in distinct brain areas including the nucleus accumbens is involved in the consolidation of SRM in laboratory mice.
在实验室中,小鼠的长期社会识别记忆(SRM)极易受到前摄干扰和倒摄干扰的影响。在此,我们研究新设计的多巴胺(DA)再摄取抑制剂(-CE-123和-CE-123)分别阻断倒摄干扰和前摄干扰的能力。我们的数据表明,在学习前30分钟给予-CE-123可阻断在学习后3小时而非6小时实验诱导的倒摄干扰。相反,在学习前30分钟给予该药物可阻断在学习后6小时而非3小时倒摄干扰的诱导。给予-CE-123在3小时和6小时均未能干扰前摄干扰。对记忆任务期间收集的其他行为参数的分析表明,新的DA再摄取抑制剂对倒摄干扰和前摄干扰的影响不能轻易地用对动物一般社会行为的非特异性影响来解释。此外,我们使用脑内微透析技术评估了药物的作用机制。结果显示,给予-CE-123和-CE-123剂量依赖性地增加了自由活动小鼠伏隔核内的DA释放。因此,本研究的数据表明,所测试的DA再摄取抑制剂可保护长期社会记忆在学习后的特定时间段内的巩固免受干扰。此外,数据表明包括伏隔核在内的不同脑区中的DA信号传导参与了实验室小鼠中SRM的巩固。