Alpha 2A adrenergic receptor agonist, guanfacine, attenuates cocaine-related impairments of inhibitory response control and working memory in animal models.
Alpha 2A adrenergic receptor agonist, guanfacine, attenuates cocaine-related impairments of inhibitory response control and working memory in animal models.
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DOI：
10.1016/j.pbb.2014.09.010
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Plagenhoef M
中科院分区：
文献类型：
--
作者：
Terry AV Jr;Callahan PM;Schade R;Kille NJ;Plagenhoef M
有大量证据表明，中枢作用的α2A肾上腺素受体激动剂可以减轻由前额皮质功能障碍引起的执行功能障碍。这些积极的影响导致了最近美国食品和药物管理局（FDA）批准α2A激动剂可口定和胍法辛用于治疗注意力缺陷/多动障碍（ADHD），但也表明它们可能对药物滥用障碍和其他神经精神疾病有有益的影响。本研究的目的是评估胍法辛在训练大鼠执行持续注意任务、五选择系列反应时间任务（5C-SRTT）和训练猴子执行工作/短期记忆任务、延迟匹配样本任务（DMTS）时，减轻与急性可卡因暴露相关的行为改变的能力。在啮齿动物5C-SRTT中，急性腹腔注射可卡因（3.5-15.0 mg/kg）不影响准确性，但与过早反应和超时反应的剂量依赖性增加有关。胍法辛（0.1-1.0 mg/kg i.p）剂量依赖性地降低了与可卡因相关的过早反应和超时反应，并减弱了在可变ITI版本的5C-SRTT中观察到的抑制反应控制的类似缺陷。在猴子的DMTS任务中，急性肌肉注射可卡因（4.0 mg/kg）与长延迟间隔的准确性受损有关，胍法辛（0.4 mg/kg）减弱了这种影响。这些动物研究表明，胍法辛可能具有治疗与可卡因滥用有关的执行功能损伤的治疗潜力。
There is considerable evidence that centrally acting α2A adrenergic receptor agonists can attenuate impairments in executive function that result from dysfunction of the prefrontal cortex. Such positive effects resulted in the recent approval by the United States Food and Drug Administration (FDA) of the α2A agonists clonidine and guanfacine for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD), but also suggest that they could have beneficial effects in substance abuse disorders and other neuropsychiatric conditions. The purpose of this study was to evaluate guanfacine for its ability to attenuate behavioral alterations associated with acute cocaine exposure in rats trained to perform a task of sustained attention, the five choice serial reaction time task (5C-SRTT) and monkeys trained to perform a task of working/short term memory, the delayed match to sample task (DMTS). In the rodent 5C-SRTT acute intraperitoneal (i.p.) administration of cocaine (3.5–15.0 mg/kg) did not affect accuracy, but was associated with dose-dependent increases in premature responses and timeout responses. Guanfacine (0.1–1.0 mg/kg i.p.) dose-dependently decreased premature responses and timeout responses associated with cocaine and it attenuated similar deficits in inhibitory response control observed in a variable ITI version of the 5C-SRTT. In the DMTS task in monkeys, acute intramuscular (i.m.) administration of cocaine (4.0 mg/kg) was associated with impairments in accuracy at long delay intervals, an effect that was attenuated by guanfacine (0.4 mg/kg). These animal studies suggest that guanfacine may have therapeutic potential for treating impairments of executive function that are associated with the abuse of cocaine.
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影响因子：
4.7
作者：
Callahan PM;Hutchings EJ;Kille NJ;Chapman JM;Terry AV Jr
通讯作者：
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3.4
作者：
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作者：
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作者：
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作者：
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通讯作者：
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