Laboratorio de Neurofarmacología de los Procesos de Memoria, Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Behav Brain Res. 2011 Jul 7;220(2):319-24. doi: 10.1016/j.bbr.2011.02.016. Epub 2011 Feb 17.
Intracellular levels of the second messengers cAMP and cGMP are maintained through a balance between production, carried out by adenyl cyclase (AC) and guanylyl cyclase (GC), and degradation, carried out by phosphodiesterases (PDEs). Recently, PDEs have gained increased attention as potential new targets for cognition enhancement, with particular reference to phosphodiesterase type 5 (PDE5A). It is accepted that once consolidation is completed memory becomes permanent, but it has also been suggested that reactivation (memory retrieval) of the original memory makes it sensitive to the same treatments that affect memory consolidation when given after training. This new period of sensitivity coined the term reconsolidation. Sildenafil (1, 3, and 10mg/kg, ip), a cGMP-PDE5 inhibitor, facilitated retention performance of a one-trial step-through inhibitory avoidance task, when administered to CF-1 male mice immediately after retrieval. The effects of sildenafil (1mg/kg, ip) were time-dependent, long-lasting and inversely correlated with memory age. The administration of sildenafil (1mg/kg, ip) 30 min prior to the 2nd retention test did not affect retention of mice given post-retrieval injections of either vehicle or sildenafil (1mg/kg, ip). Finally, an enhancement of retention was also observed in CF-1 female mice receiving sildenafil (1mg/kg, ip) immediately, but not 180 min after retrieval. In the present paper we reported for the first time that systemic administration of sildenafil after memory reactivation enhances retention performance of the original learning. Our results indirectly point out cGMP, a component of the NO/cGMP/PKG pathway, as a necessary factor for memory reconsolidation.
细胞内第二信使 cAMP 和 cGMP 的水平通过其产生（由腺苷酸环化酶（AC）和鸟苷酸环化酶（GC）完成）和降解（由磷酸二酯酶（PDE）完成）之间的平衡来维持。最近，磷酸二酯酶（PDE）作为认知增强的潜在新靶点引起了更多关注，特别是磷酸二酯酶 5（PDE5A）。人们普遍认为，一旦巩固完成，记忆就会永久存在，但也有人提出，原始记忆的再激活（记忆检索）使其对在训练后给予的影响记忆巩固的相同治疗敏感。这一新的敏感时期被称为再巩固。西地那非（1、3 和 10mg/kg，ip），一种 cGMP-PDE5 抑制剂，当给予 CF-1 雄性小鼠在检索后立即给予时，可促进单次试验一步式回避任务的保留表现。西地那非（1mg/kg，ip）的作用具有时间依赖性、持久性，并与记忆年龄呈负相关。在第二次保留测试前 30 分钟给予西地那非（1mg/kg，ip）不会影响给予检索后给予载体或西地那非（1mg/kg，ip）的小鼠的保留。最后，还观察到 CF-1 雌性小鼠在检索后立即接受西地那非（1mg/kg，ip）治疗也可增强保留。在本文中，我们首次报道全身给予西地那非可增强原始学习的记忆再激活后的保留表现。我们的结果间接指出 cGMP（NO/cGMP/PKG 途径的一个组成部分）作为记忆再巩固的必要因素。
