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.

译文

我们研究了具有抗焦虑特性的cholecystokinin-4的逆转类似物二肽GB-115对近交大鼠和cholecystokinin-4受体激动剂和育亨宾诱导的BALB/c和C57Bl/6小鼠行为的影响。在野外试验和高架迷宫试验中,已显示出抗焦虑剂可引起大鼠和C57Bl/6小鼠的焦虑 (对压力有积极反应),但并未调节BALB/c小鼠的行为表现出对情感的冻结反应暴露。cholecystokinin-4 2型受体的激活消除了BALB/c小鼠GB-115的抗焦虑作用。这种二肽阻止了C57Bl/6小鼠和近交大鼠cholecystokinin-4-induced焦虑的发展。Α (2)-肾上腺素能受体拮抗剂育亨宾不调节BALB/c小鼠中GB-115的作用。GB-115不能阻止育亨宾诱导的C57Bl/6小鼠焦虑的发展。我们的结果证实了GB-115表型特异性活性的数据。我们得出结论,cholecystokinin-4和GB-115具有共同的药理学靶标。

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