The nicotine metabolite, cotinine, attenuates glutamate (NMDA) antagonist-related effects on the performance of the five choice serial reaction time task (5C-SRTT) in rats.
The nicotine metabolite, cotinine, attenuates glutamate (NMDA) antagonist-related effects on the performance of the five choice serial reaction time task (5C-SRTT) in rats.
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尼古丁代谢物可替宁可减弱谷氨酸 (NMDA) 拮抗剂对大鼠五选择系列反应时间任务 (5C-SRTT) 表现的影响。
DOI：
10.1016/j.bcp.2011.12.043
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发表时间：
2012
影响因子：
5.8
通讯作者：
Bartlett,MichaelG
中科院分区：
文献类型：
--
作者：
TerryJr,AlvinV;Buccafusco,JerryJ;Schade,RFoster;Vandenhuerk,Leah;Callahan,PatrickM;Beck,WayneD;Hutchings,ElizabethJ;Chapman,JamesM;Li,Pei;Bartlett,MichaelG
可替宁是尼古丁在哺乳动物中最主要的代谢产物，其药理学半衰期大大超过其前体。然而，直到最近，相对较少的研究已经进行了系统地表征可替宁的行为药理学。我们之前的工作表明，可替宁可以改善药理学损伤模型中大鼠听觉惊吓反应的前脉冲抑制，并且可以改善非人类灵长类动物的工作记忆。在这里，我们测试的假设，可替宁提高持续的注意力在大鼠和减弱行为改变引起的谷氨酸（NMDA）拮抗剂MK-801。在固定和可变刺激持续时间（VSD）以及可变试验间隔（VITI）的五选择系列反应时任务（5C-SRTT）中评价了急性皮下（剂量范围0.03-10.0mg/kg）和慢性口服（饮用水中2.0mg/kg/天）可替宁的作用。结果表明，急性可替宁（单独给药）对5C-SRTT的性能仅有轻微影响（例如，超时响应减少）。然而，根据剂量，可替宁急性治疗可减弱MK-801相关的准确性损害和超时反应升高，并增加已完成试验的数量。此外，慢性可替宁减弱了MK-801相关的准确性损伤，并且当任务需求增加时，它减少了过早和超时反应（即，通过除了给予MK-801之外还呈现VSD或葡萄属）。这些数据表明，可替宁可能代表了对神经精神障碍具有治疗潜力的化合物的原型（即，通过改善持续的注意力和减少冲动和强迫行为），特别是那些以谷氨酸受体改变为特征的行为。
Cotinine, the most predominant metabolite of nicotine in mammalian species, has a pharmacological half-life that greatly exceeds its precursor. However, until recently, relatively few studies had been conducted to systematically characterize the behavioral pharmacology of cotinine. Our previous work indicated that cotinine improves prepulse inhibition of the auditory startle response in rats in pharmacological impairment models and that it improves working memory in non-human primates. Here we tested the hypothesis that cotinine improves sustained attention in rats and attenuates behavioral alterations induced by the glutamate (NMDA) antagonist MK-801. The effects of acute subcutaneous (dose range 0.03–10.0mg/kg) and chronic oral administration (2.0mg/kg/day in drinking water) of cotinine were evaluated in fixed and variable stimulus duration (VSD) as well as variable intertrial interval (VITI) versions of a five choice serial reaction time task (5C-SRTT). The results indicated only subtle effects of acute cotinine (administered alone) on performance of the 5C-SRTT (e.g., decreases in timeout responses). However, depending on dose, acute treatment with cotinine attenuated MK-801-related impairments in accuracy and elevations in timeout responses, and it increased the number of completed trials. Moreover, chronic cotinine attenuated MK-801-related impairments in accuracy and it reduced premature and timeout responses when the demands of the task were increased (i.e., by presenting VSDs or VITIs in addition to administering MK-801). These data suggest that cotinine may represent a prototype for compounds that have therapeutic potential for neuropsychiatric disorders (i.e., by improving sustained attention and decreasing impulsive and compulsive behaviors), especially those characterized by glutamate receptor alterations.
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DOI：
10.1016/j.bbamcr.2007.12.003
发表时间：
2008-03-01
影响因子：
5.1
作者：
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DOI：
--
发表时间：
1995
期刊：
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影响因子：
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DOI：
--
发表时间：
1993
期刊：
Pharmacology, Biochemistry and Behavior
影响因子：
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DOI：
--
发表时间：
1992
期刊：
International Journal of Radiation Applications and Instrumentation Part B Nuclear Medicine and Biology
影响因子：
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