Differential effects of nomifensine and imipramine on motivated behavior in the runway model of intracranial self-stimulation.
Differential effects of nomifensine and imipramine on motivated behavior in the runway model of intracranial self-stimulation.
复制标题
诺米芬辛和丙咪嗪对颅内自我刺激跑道模型中动机行为的不同影响。
DOI：
10.1016/j.ejphar.2013.09.079
复制
发表时间：
2013
影响因子：
5
通讯作者：
Sendo T.
中科院分区：
文献类型：
--
作者：
Esumi S;Kawasaki Y;Nakamoto A;Sagara H;Gomita Y;Kitamura Y;Sendo T.
动机缺陷（对以前的奖励刺激失去乐趣或兴趣）是重性抑郁症的核心症状之一，需要有效的模型来评估药物的动机作用。颅内自我刺激（ICSS）跑道模型中的启动刺激效应可以作为研究药物激励效应的模型系统。然而，这种新的实验模型的特点还没有完全阐明。在这项研究中，我们研究了诺米芬辛和丙咪嗪在跑道ICSS模型，强迫游泳测试，和自发活动测试，以区分动机从情感样状态的影响。诺米芬辛剂量依赖性地增加跑道上的跑步速度，并减少强迫游泳测试中的不动时间。相比之下，丙咪嗪降低跑道上的跑步速度，虽然它也减少了不动时间在强迫游泳测试。此外，在跑道模型中的动机增强作用的诺米芬辛完全抑制预处理与多巴胺受体拮抗剂氟哌啶醇，虽然诺米芬辛诱导的运动增加不受氟哌啶醇。这些结果表明，诺米芬辛显示动机增强和抗抑郁样作用。此外，在跑道ICSS模型中，诺米芬新的动机作用主要由多巴胺受体介导，并且动机行为的增强并不简单地反映过度运动。
A motivational deficit (the loss of pleasure or interest in previously rewarding stimuli) is one of the core symptoms of major depression, and valid models evaluating the motivational effects of drugs are needed. It was recently demonstrated that the priming stimulation effect in the runway model of intracranial self-stimulation (ICSS) can be used as a model system to study the motivational effects of drugs. However, the characteristics of this novel experimental model have not been fully clarified. In this study, we investigated the effects of nomifensine and imipramine in the runway ICSS model, forced swim tests, and locomotor activity tests to differentiate motivation from affective-like states. Nomifensine dose-dependently increased running speed on the runway and decreased immobility time in the forced swim test. In contrast, imipramine decreased running speed on the runway although it also decreased immobility time in the forced swim test. In addition, the motivation-enhancing effect of nomifensine in the runway model was completely inhibited by pretreatment with the dopamine receptor antagonist haloperidol, although nomifensine-induced increases in locomotion were not affected by haloperidol. These results demonstrate that nomifensine displays motivation-enhancing and antidepressant-like effects. In addition, the motivational effects of nomifensine in the runway ICSS model are primarily mediated by dopamine receptors and enhancements of motivated behavior do not simply reflect hyperlocomotion.