PDF(Pubmed)
Abstract：
Adenylyl cyclase 1 (AC1) is a selective subtype of ACs, which is selectively expressed in neurons. The activation of AC1 is activity-dependent, and AC1 plays an important role in cortical excitation that contributes to chronic pain and related emotional disorders. Previous studies have reported that human-used NB001 (hNB001, a selective AC1 inhibitor) produced analgesic effects in different animal models of chronic pain. However, the potential effects of hNB001 on learning and memory have been less investigated. In the present study, we found that hNB001 affected neither the induction nor the expression of trace fear, but selectively enhanced the relearning ability during the extinction in aged mice. By contrast, the same application of hNB001 did not affect recent, remote auditory fear memory, or remote fear extinction in either adult or aged mice. Furthermore, a single or consecutive 30-day oral administration of hNB001 did not affect acute nociceptive response, motor function, or anxiety-like behavior in either adult or aged mice. Our results are consistent with previous findings that inhibition of AC1 did not affect general sensory, emotional, and motor functions in adult mice, and provide strong evidence that inhibiting the activity of AC1 may be beneficial for certain forms of learning and memory in aged mice.
摘要：
腺苷酸环化酶1（AC1）是一种选择性的ACs亚型，在神经元中选择性表达。AC1的激活是活性依赖性的，AC1在导致慢性疼痛和相关情绪障碍的皮质兴奋中起重要作用。先前的研究报道，人类使用的NB001（hNB001，一种选择性AC1抑制剂）在不同的慢性疼痛动物模型中产生了镇痛作用。然而,hNB001对学习和记忆的潜在影响研究较少。在本研究中,我们发现hNB001既不影响痕量恐惧的诱导也不影响其表达,但选择性地增强了老年小鼠灭绝期间的再学习能力。相比之下,HNB001的相同应用没有影响最近，远程听觉恐惧记忆，或在成年或成年小鼠中远程恐惧灭绝。此外，单次或连续30天口服hNB001不影响急性伤害性反应，运动功能,或成年或老年小鼠的焦虑样行为。我们的结果与先前的发现一致，即抑制AC1不影响一般感觉，情感,和成年小鼠的运动功能，并提供强有力的证据表明，抑制AC1的活性可能对老年小鼠的某些形式的学习和记忆有益。
