Franowicz J S, Arnsten A F
Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06520-8001, USA.
Psychopharmacology (Berl). 1998 Mar;136(1):8-14. doi: 10.1007/s002130050533.
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.
在患有自然发生的儿茶酚胺耗竭的老年猴子中，胍法辛等α-2肾上腺素能激动剂已多次被证明可改善背外侧前额叶皮质功能，这是通过空间延迟反应任务评估得出的。低剂量（0.0001-0.001毫克/千克）和高剂量（0.5毫克/千克）的胍法辛可改善老年动物的空间工作记忆表现，但中等剂量（0.01-0.05毫克/千克）则无此作用。然而，尚不清楚胍法辛是否会同样改善年轻动物的表现。在本研究中，对7只年轻成年恒河猴进行了胍法辛对延迟反应表现影响的研究。低剂量的胍法辛（0.0001-0.01毫克/千克）对任务表现无影响，而高剂量的胍法辛（0.1-0.7毫克/千克）则显著改善了任务表现。最高剂量产生了轻度镇静作用，这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毫克/千克）对最有效剂量的胍法辛进行了挑战。单独给予该剂量的咪唑克生对任务表现无影响。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。这些结果支持了这样一种假设，即年轻完整动物的延迟反应表现可通过作用于α-2肾上腺素能受体而得到改善。
