Role of the cholecystokinin system in anxiolytic activity of dipeptide GB-115.

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.