Dèpartement de Psychologie, Cognition and Comportement, Université de Liège, Liège, Belgium.
Neuroscience. 2011 Oct 13;193:132-42. doi: 10.1016/j.neuroscience.2011.07.034. Epub 2011 Jul 28.
Albeit there is no doubt that histamine and its H(3) receptors participate in several aspects of learning and memory, such as memory consolidation, nothing is known about their potential involvement in memory reconsolidation. On the basis of previous reports of pro-cognitive effects of histamine H(3) receptor inverse agonists (which augment histamine release), we investigated to what extent the most representative of them, thioperamide, is able to facilitate reconsolidation of a contextually-conditioned fear memory in C57BL/6J mice. We also examined the effects of thioperamide on the stark disruptive effect that the non-competitive N-methyl-d-aspartate (NMDA) antagonist dizocilpine (MK-801) typically exerts on both reconsolidation and consolidation. Post-training systemic injections (i.p.) of thioperamide facilitated consolidation at 10 and 20 mg/kg and reversed amnesia induced by an i.p. injection of 0.12 mg/kg dizocilpine at 5, 10 and 20 mg/kg. Importantly, none of the five thioperamide doses (2.5, 5, 10, 20 and 30 mg/kg) given right after reactivation (reexposure to the context in which training took place 48 h earlier) affected reconsolidation, whereas all similarly given doses of dizocilpine (0.03, 0.06 and 0.12 mg/kg) disrupted it more or less equally. By contrast, thioperamide was able to unambiguously reverse the deficit in reconsolidation induced by 0.12 mg/kg dizocilpine at 10 and 20, but not 5 mg/kg. This is the first demonstration of an involvement of the interactive articulation between histamine and NMDA receptors in the mechanisms of memory reconsolidation, which seems to be indifferent to an increase of brain histamine per se. The results suggest a qualitatively different participation of histaminergic signalling in the mechanisms of reconsolidation and consolidation. The precise circuits within which these interactions take place are yet to be identified.
尽管毫无疑问，组胺及其 H（3）受体参与了学习和记忆的多个方面，例如记忆巩固，但对于它们在记忆再巩固中的潜在作用仍一无所知。基于组胺 H（3）受体反向激动剂（增强组胺释放）具有认知促进作用的先前报道，我们研究了最具代表性的噻哌酰胺（thioperamide）在多大程度上能够促进 C57BL/6J 小鼠的情境条件性恐惧记忆的再巩固。我们还检查了噻哌酰胺对非竞争性 N-甲基-D-天冬氨酸（NMDA）拮抗剂地卓西平（MK-801）对再巩固和巩固均具有明显破坏作用的影响。在训练后进行全身注射（i.p.）噻哌酰胺可促进 10 和 20 mg/kg 剂量的巩固，并逆转 0.12 mg/kg 地卓西平（i.p.注射）在 5、10 和 20 mg/kg 剂量下引起的健忘症。重要的是，在再激活后（在 48 小时前进行训练的情境中重新暴露）给予的五个噻哌酰胺剂量（2.5、5、10、20 和 30 mg/kg）均未影响再巩固，而所有类似给予的地卓西平剂量（0.03、0.06 和 0.12 mg/kg）或多或少都会破坏再巩固。相比之下，噻哌酰胺能够明确逆转 0.12 mg/kg 地卓西平在 10 和 20 mg/kg 但不能在 5 mg/kg 剂量下引起的再巩固缺陷。这是首次证明组胺和 NMDA 受体之间的相互作用在记忆再巩固的机制中发挥作用，这似乎与大脑组胺本身的增加无关。这些结果表明，在再巩固和巩固的机制中，组胺能信号传递的参与具有不同的性质。这些相互作用发生的确切回路仍有待确定。
