Kolik L G, Gudasheva T A, Seredenin S B
V. V. Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, Russia.
Bull Exp Biol Med. 2012 Oct;153(6):851-4. doi: 10.1007/s10517-012-1842-1.
We studied the effect of dipeptide GB-115, a retroanalogue of cholecystokinin-4 with anxiolytic properties, on the behavior of outbred rats and BALB/c and C57Bl/6 mice induced by cholecystokinin-4 receptor agonists and yohimbine. Anxiogenic agents were shown to cause anxiety in rats and C57Bl/6 mice (with an active response to stress) in the open field test and elevated plus maze test, but did not modulate the behavior of BALB/c mice exhibiting a freezing response to emotiogenic exposure. Activation of cholecystokinin-4 type 2 receptors abolished the antianxiety effect of GB-115 in BALB/c mice. This dipeptide prevented the development of cholecystokinin-4-induced anxiety in C57Bl/6 mice and outbred rats. α(2)-Adrenoceptor antagonist yohimbine did not modulate the effects of GB-115 in BALB/c mice. GB-115 did not prevent the development of yohimbine-induced anxiety in C57Bl/6 mice. Our results confirm the data on phenotype-specific activity of GB-115. We conclude that cholecystokinin-4 and GB-115 have a common pharmacological target.
我们研究了具有抗焦虑特性的胆囊收缩素-4反向类似物二肽GB-115对远交系大鼠以及BALB/c和C57Bl/6小鼠行为的影响，这些行为由胆囊收缩素-4受体激动剂和育亨宾诱导产生。在旷场试验和高架十字迷宫试验中，致焦虑剂被证明会使大鼠和C57Bl/6小鼠（对应激有积极反应）产生焦虑，但对情绪源性暴露表现出僵住反应的BALB/c小鼠的行为没有调节作用。胆囊收缩素-4 2型受体的激活消除了GB-115对BALB/c小鼠的抗焦虑作用。这种二肽可预防C57Bl/6小鼠和远交系大鼠中胆囊收缩素-4诱导的焦虑的发生。α(2)-肾上腺素能受体拮抗剂育亨宾对GB-115在BALB/c小鼠中的作用没有调节作用。GB-115不能预防C57Bl/6小鼠中育亨宾诱导的焦虑的发生。我们的结果证实了关于GB-115表型特异性活性的数据。我们得出结论，胆囊收缩素-4和GB-115有共同的药理学靶点。
