title: Role of the cholecystokinin system in anxiolytic activity of dipeptide GB-115.
abstract: 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.
authors.affiliation: V. V. Zakusov Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, Russia. lgkolik@mail.ru
authors.forename: L G
authors.initials: LG
authors.lastname: Kolik
authors.forename: T A
authors.initials: TA
authors.lastname: Gudasheva
authors.forename: S B
authors.initials: SB
authors.lastname: Seredenin
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology* / Q000627:therapeutic use; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D051381:Rats; D043887:Receptor, Cholecystokinin B / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013045:Species Specificity; D013758:Tetragastrin; D015016:Yohimbine
chemical_list: D014151:Anti-Anxiety Agents; D004151:Dipeptides; C520797:GB-115; D043887:Receptor, Cholecystokinin B; D013758:Tetragastrin; D015016:Yohimbine