Modulation of hippocampal dopamine metabolism and hippocampal-dependent cognitive function by catechol-O-methyltransferase inhibition.
Modulation of hippocampal dopamine metabolism and hippocampal-dependent cognitive function by catechol-O-methyltransferase inhibition.
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DOI：
10.1177/0269881112454228
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发表时间：
2012-12
期刊：
影响因子：
--
通讯作者：
Tunbridge EM
中科院分区：
文献类型：
--
作者：
Laatikainen LM;Sharp T;Bannerman DM;Harrison PJ;Tunbridge EM
儿茶酚-O-甲基转移酶（COMT）分解代谢儿茶酚胺类神经递质，影响认知功能。COMT调节前额叶皮层的多巴胺水平，它在这一区域的作用通常被用来解释它对认知的影响。然而，它在其他对认知功能重要的大脑区域中的作用在很大程度上仍未被探索。在这里，我们研究了COMT对海马多巴胺代谢和海马依赖行为的影响。我们检测了中枢作用COMT抑制剂托卡朋（30 mg/kg i. p.）在大鼠背海马多巴胺代谢，评估组织匀浆和细胞外，使用体内微透析。此外，我们还研究了托卡朋对依赖于背侧海马的延迟-奖励交替和空间新奇偏好行为任务的影响。托卡朋显著调节背海马中的多巴胺代谢，如通过细胞外高香草酸（HVA）的消耗和二羟基苯乙酸（DOPAC）的积累所指示的。托卡朋也提高了性能的延迟奖励交替和空间新奇偏好任务，相比，车辆处理的大鼠。我们的研究结果表明，COMT调节背海马神经化学和调制海马依赖的行为。这些发现支持COMT抑制作为认知增强剂的治疗候选资格，并表明，除了前额叶皮层，海马可能是介导这些效应的关键区域。
Catechol-O-methyltransferase (COMT) catabolises the catecholamine neurotransmitters and influences cognitive function. COMT modulates dopamine levels in the prefrontal cortex and its action in this region is generally invoked to explain its effects on cognition. However, its role in other brain regions important for cognitive function remains largely unexplored. Here, we investigated COMT’s impact on dopamine metabolism in the hippocampus and hippocampal-dependent behaviour. We examined the acute effects of a centrally-acting COMT inhibitor, tolcapone (30 mg/kg i.p.), on dopamine metabolism in the rat dorsal hippocampus, assessed both in tissue homogenates and extracellularly, using in vivo microdialysis. Additionally, we investigated the effect of tolcapone on delayed-rewarded alternation and spatial novelty preference, behavioural tasks which are dependent on the dorsal hippocampus. Tolcapone significantly modulated dopamine metabolism in the dorsal hippocampus, as indexed by the depletion of extracellular homovanillic acid (HVA) and the accumulation of dihydroxyphenylacetic acid (DOPAC). Tolcapone also improved performance on the delayed-rewarded alternation and spatial novelty preference tasks, compared to vehicle-treated rats. Our findings suggest that COMT regulates dorsal hippocampal neurochemistry and modulates hippocampus-dependent behaviours. These findings support the therapeutic candidacy of COMT inhibition as a cognitive enhancer, and suggest that, in addition to the prefrontal cortex, the hippocampus might be a key region for mediating these effects.
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DOI：
10.1073/pnas.111134598
发表时间：
2001-06-05
影响因子：
11.1
作者：
Egan, MF;Goldberg, TE;Weinberger, DR
通讯作者：
Weinberger, DR
影响因子：
10.6
作者：
Barnett, Jennifer H.;Scoriels, Linda;Munafo, Marcus R.
通讯作者：
Munafo, Marcus R.
影响因子：
4.7
作者：
ACQUAS, E;CARBONI, E;DICHIARA, G
通讯作者：
DICHIARA, G
影响因子：
3.4
作者：
Dias, R;Aggleton, JP
通讯作者：
Aggleton, JP
影响因子：
2.6
作者：
de Frias, CM;Annerbrink, K;Nilsson, LG
通讯作者：
Nilsson, LG