The α-2a noradrenergic agonist, guanfacine, improves delayed response performance in young adult rhesus monkeys
The α-2a noradrenergic agonist, guanfacine, improves delayed response performance in young adult rhesus monkeys
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DOI：
10.1007/s002130050533
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发表时间：
1998-03-01
影响因子：
3.4
通讯作者：
Arnsten, AFT
中科院分区：
文献类型：
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作者：
Franowicz, JS;Arnsten, AFT
在自然发生的儿茶酚胺耗竭的老年猴中，α-2肾上腺素能激动剂如胍法辛已多次被证明可改善背外侧前额叶皮质功能，如通过空间延迟反应任务评估的。低剂量（0.0001-0.001 mg/kg）和高剂量（0.5 mg/kg）但不中等剂量（0.01-0.05 mg/kg）的胍法辛均改善老年动物的空间工作记忆表现。然而，目前还不知道胍法辛是否会同样改善年轻动物的表现。在本研究中，胍法辛对延迟反应性能的影响，其特征在于在7个年轻的成年恒河猴。低剂量胍法辛（0.0001-0.01 mg/kg）对任务绩效没有影响，而高剂量胍法辛（0.1-0.7 mg/kg）显著改善任务绩效。最高剂量产生轻度镇静，与药物对延迟反应的影响无关。用α-2拮抗剂咪唑克生（0.1 mg/kg）激发最有效剂量的胍法辛。当单独给予该剂量的咪唑克生时，对任务表现没有影响。与α-2机制一致，咪唑克生显著降低了胍法辛治疗动物的延迟反应表现。这些结果支持了这一假设，即在年轻的完整的动物延迟反应性能可以通过α-2肾上腺素能受体的行动得到改善。
In aged monkeys with naturally occurring catecholamine depletion, alpha-2 adrenergic agonists such as guanfacine have repeatedly been shown to improve dorsolateral prefrontal cortical function, as assessed by the spatial delayed response task. Both low (0.0001-0.001 mg/kg) and high (0.5 mg/kg) but not intermediate (0.01-0.05 mg/kg) doses of guanfacine improve spatial working memory performance in aged animals. However, it is not known whether guanfacine would similarly improve performance in young animals. In the present study, the effects of guanfacine on delayed response performance were characterized in seven young adult rhesus monkeys. Low doses of guanfacine (0.0001-0.01 mg/kg) had no effect on task performance, while high doses of guanfacine (0.1-0.7 mg/kg) significantly improved task performance. The highest doses produced mild sedation that was independent of drug effects on delayed response. The most effective dose of guanfacine was challenged with the alpha-2 antagonist idazoxan (0.1 mg/kg). This dose of idazoxan had no effect on task performance when given alone. Consistent with an alpha-2 mechanism, idazoxan significantly decreased delayed response performance in guanfacine-treated animals. These results support the hypothesis that delayed response performance in young intact animals can be improved through actions at alpha-2 adrenergic receptors.