Département de Psychologie, Cognition et Comportement, Université de Liège, Boulevard du Rectorat 5/B32, B-4000 Liège, Belgium.
Behav Brain Res. 2013 Sep 15;253:121-7. doi: 10.1016/j.bbr.2013.07.016. Epub 2013 Jul 15.
Numerous studies have found that histamine plays a major role in memory and that the histamine H3 receptor (H3R) inverse agonist thioperamide improves cognitive performance in various animal models. However, little is known about the stages of memory that are specifically affected by thioperamide. The purpose of the present study was to investigate the effects of thioperamide on acquisition, consolidation and retrieval processes in a one-trial inhibitory avoidance task in female C57BL/6J mice. In addition, potential state-dependency effects were studied by injecting thioperamide before the training and the test sessions in order to induce similar physiological states during acquisition and retrieval. Our results indicate that post-training systemic administration of thioperamide facilitated consolidation. Moreover, the administration of thioperamide before the training session had no effect on latency to enter the black compartment during training but enhanced memory during the retention test. The administration of thioperamide before the retention test also increased performance, which indicates that this compound ameliorates memory retrieval. Finally, when animals received thioperamide before the training session and before the retention test, the cognitive enhancing effects of thioperamide were not significantly changed. Together, our results show that thioperamide improves cognitive performance in an inhibitory avoidance task through actions on different memory stages. Furthermore, inducing a similar physiological state with thioperamide during acquisition and retrieval do not significantly affect cognitive enhancement. Our results suggest that the blockade of H3R can be helpful for the treatment of neuropsychiatric conditions characterized by deficits affecting several stages of memory processing.
许多研究发现，组胺在记忆中起着重要作用，组胺 H3 受体（H3R）反向激动剂噻哌酰胺可改善各种动物模型的认知表现。然而，人们对噻哌酰胺具体影响的记忆阶段知之甚少。本研究的目的是在雌性 C57BL/6J 小鼠的单次抑制回避任务中研究噻哌酰胺对获得、巩固和检索过程的影响。此外，通过在训练和测试期间注射噻哌酰胺来研究潜在的状态依赖性效应，以便在获得和检索期间诱导相似的生理状态。我们的结果表明，训练后系统给予噻哌酰胺可促进巩固。此外，在训练期间给予噻哌酰胺前给药对进入黑箱的潜伏期没有影响，但在保留测试中增强了记忆。在保留测试前给予噻哌酰胺也增加了性能，表明该化合物改善了记忆检索。最后，当动物在训练前给药和保留测试前给药时，噻哌酰胺的认知增强作用没有明显变化。综上所述，噻哌酰胺通过作用于不同的记忆阶段来改善抑制回避任务中的认知表现。此外，在获得和检索期间用噻哌酰胺诱导相似的生理状态不会显著影响认知增强。我们的结果表明，阻断 H3R 可能有助于治疗以影响记忆处理多个阶段为特征的神经精神疾病。
