首页> 美国卫生研究院文献>Neuropsychopharmacology >Chronic Corticosterone Exposure during Adolescence Reduces Impulsive Action but Increases Impulsive Choice and Sensitivity to Yohimbine in Male Sprague-Dawley Rats
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Chronic Corticosterone Exposure during Adolescence Reduces Impulsive Action but Increases Impulsive Choice and Sensitivity to Yohimbine in Male Sprague-Dawley Rats

机译:青春期慢性皮质酮暴露可减少冲动行为但会增加雄性Sprague-Dawley大鼠的冲动选择和对育亨宾的敏感性。

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摘要

Chronic stress during adolescence is associated with an increased risk for alcoholism and addictive disorders. Addiction is also associated with increased impulsivity, and stress during adolescence could alter cortical circuits responsible for response inhibition. Therefore, the present study determined the effect of chronic exposure to the stress hormone corticosterone (CORT) during adolescence on tests of impulsivity in adulthood and examined possible biochemical mechanisms. Male Sprague-Dawley rats were exposed to CORT by their drinking water during adolescence (post-natal day 30–50). The rats were then tested in adulthood to assess behavior on the 5-choice serial reaction time task (5CSRTT), stop-signal reaction time task (SSRTT), and the delay-discounting task, which differentially assess attention, impulsive action, and impulsive choice. Yohimbine-induced impulsivity on the 5CSRTT and biochemical analysis of the lateral orbital frontal cortex (lOFC) was also assessed owing to the ability of yohimbine to activate the hypothalamic-pituitary-adrenal axis and influence impulsivity. Adolescent CORT-treated rats were found to behave largely like controls on the 5CSRTT, but did show reduced premature responses when the intertrial interval was increased. Nevertheless, the CORT-treated rats tended to have more yohimbine-induced impulsive responses at low doses on this task, which was not found to be due to increased pCREB in the lOFC, but could be related to a higher expression/activity of the AMPA receptor subunit GluR1. Adolescent CORT-treated rats performed more accurately on the SSRTT, but showed greater impulsivity on the delay-discounting task, as indicated by steeper discounting functions. Therefore, adolescent CORT exposure reduced impulsive action but increased impulsive choice, indicating that chronic stress hormone exposure in adolescence can have long-term consequences on behavior.
机译:青春期的慢性应激与酗酒和成瘾性疾病的风险增加有关。成瘾还与冲动性增加有关,青春期的压力可能会改变负责抑制反应的皮层回路。因此,本研究确定了青春期长期暴露于应激激素皮质酮(CORT)对成年冲动测试的影响,并研究了可能的生化机制。雄性Sprague-Dawley大鼠在青春期(产后30–50天)通过饮水接触了CORT。然后在成年期对大鼠进行测试,以评估其五项选择系列反应时间任务(5CSRTT),停止信号反应时间任务(SSRTT)和延迟折扣任务的行为,从而分别评估注意力,冲动行为和冲动选择。由于育亨宾具有激活下丘脑-垂体-肾上腺轴并影响冲动的能力,因此还评估了育亨宾在5CSRTT上的冲动性和外侧眶额叶皮层(10FC)的生化分析。研究发现,用CORT青春期治疗的大鼠的行为与5CSRTT上的对照大致相同,但当间隔时间增加时,确实显示出过早的反应减少。然而,在低剂量下,经CORT治疗的大鼠在此剂量下倾向于具有更多的育亨宾诱导的冲动反应,这不是由于10FC中pCREB的增加所致,但可能与AMPA的较高表达/活性有关。受体亚基GluR1。用CORT治疗的青春期大鼠在SSRTT上的表现更为准确,但在延迟折扣任务上表现出更大的冲动,这表现为更陡峭的贴现功能。因此,青春期CORT暴露可减少冲动行为,但增加冲动选择,表明青春期慢性应激激素暴露可对行为产生长期影响。

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