Age-related declines in delayed non-match-to-sample performance (DNMS) are reversed by the novel 5HT6 receptor antagonist SB742457
Age-related declines in delayed non-match-to-sample performance (DNMS) are reversed by the novel 5HT6 receptor antagonist SB742457
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DOI：
10.1016/j.neuropharm.2012.06.034
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发表时间：
2012-10-01
影响因子：
4.7
通讯作者：
O'Mara, Shane M.
中科院分区：
文献类型：
--
作者：
Callaghan, Charlotte K.;Hok, Vincent;O'Mara, Shane M.
突触可塑性和神经认知功能随年龄的变化已在文献中得到充分记录。这些变化伴随着中枢神经系统（CNS）神经递质系统的改变。血清素系统在注意力、警觉性和认知方面发挥着特别重要的作用。血清素能功能的紊乱与不同的神经和神经精神疾病有关，包括抑郁症、精神病攻击和痴呆。血清素受体亚型5HT6分布在与学习和记忆相关的中枢神经系统区域，包括纹状体、皮质和海马体。我们在此检查了急性和慢性施用 5HT6 受体拮抗剂 SB742457 对延迟非匹配样本任务 (DNMS) 表现的影响，该任务用于识别中年（MA，13 个月）和年轻成年（YG，3 个月）大鼠之间的神经认知差异。我们发现，与 YG 大鼠相比，MA 大鼠在 DNMS 任务中的表现明显较低。 SB742457 (3 mg/kg/po) 的急性给药显着改善了 MA 大鼠的表现。长期服用 SB742457 (3 mg/kg) 可逆转与年龄相关的 MA 缺陷，使其表现与 YG 大鼠相匹配。此外，在停止 SB742457 治疗后 1 周内观察到这些改善。这种治疗的急性和慢性影响表明，不仅对神经递质作用有直接影响，而且可能对突触可塑性产生长期影响。这些数据共同表明了调节血清素系统在认知增强剂开发中的作用。 (C) 2012 Elsevier Ltd. 保留所有权利。
Alterations in synaptic plasticity and neurocognitive function with age have been well documented in the literature. These changes are accompanied by modifications of neurotransmitter systems in the central nervous system (CNS). The serotonergic system in particular plays an important role in attention, alertness and cognition. Disturbances in serotonergic function have been implicated in differing neurological and neuropsychiatric disorders including depression, psychosis aggression and dementia. The serotonin receptor subtype 5HT6 is distributed within CNS regions relevant to learning and memory, including the striatum, cortex and hippocampus. We examined here the effects of acute and chronic administration of the 5HT6 receptor antagonist SB742457 on performance in a delayed non-matching-to-sample task (DNMS), which was used to identify neurocognitive differences between middle-aged (MA, 13 months) and young adult (YG, 3 months) rats. We found that MA rats have significantly lower performance in the DNMS task compared to YG rats. Acute administration of SB742457 (3 mg/kg/po) significantly improved performance of the MA rats. Chronic administration of SB742457 (3 mg/kg) reversed the age-related deficit of the MA to match their performance to that of YG rats. Furthermore, these improvements were observed for 1 week post-SB742457 treatment cessation. The acute and chronic effects of this treatment suggest that there is both an immediate effect on neurotransmitter action and potentially a longer-term modification of synaptic plasticity. Together these data indicate a role for modulation of the serotonergic system in the development of cognition-enhancing agents. (C) 2012 Elsevier Ltd. All rights reserved.