Anxiolytic-like effect of the selective Neuropeptide Y Y2 receptor antagonist BIIE0246 in the elevated plus-maze

Neuropeptide Y and posttraumatic stress disorder

“…43 Treatment with Y2 antagonist BIIE0246 produces anxiolysis in the elevated plus maze. 44 Newer smallmolecule Y2 antagonists have produced contradictory effects. Although Y2 antagonist, JNJ-31020028 was found to reduce anxiety following alcohol withdrawal, 45 JNJ-5207787 was found to be ineffective.…”

In vitro and in vivo characterization of JNJ-31020028 (N-(4-{4-[2-(diethylamino)-2-oxo-1-phenylethyl]piperazin-1-yl}-3-fluorophenyl)-2-pyridin-3-ylbenzamide), a selective brain penetrant small molecule antagonist of the neuropeptide Y Y2 receptor

“…However, studies using knockout mice are of course limited by possible compensatory changes, and in addition, a recent study failed to observe an anxiolytic phenotype in Y 2 knockout mice from a pure C57BL background, suggesting an interaction between background genetics and phenotype (Caberlotto et al 2007). One possible difference between the previous experiment with BIIE-0246 (Bacchi et al 2006) and the current one is in the different routes of injection (i.c.v. versus systemic).…”

“…BIIE-0246 does not cross the blood-brain barrier and has a very narrow margin between efficacy and nonspecific effect (sedation) after intracerebroventricular (i.c.v.) administration (Bacchi et al 2006). In fact, no proper dose-response curve has been generated after i.c.v.…”

“…administration of BIIE-0246 suggest that Y 2 antagonists should be anxiolytic (Bacchi et al 2006;Carvajal et al 2006;Painsipp et al 2008;Redrobe et al 2003;Tschenett et al 2003). However, studies using knockout mice are of course limited by possible compensatory changes, and in addition, a recent study failed to observe an anxiolytic phenotype in Y 2 knockout mice from a pure C57BL background, suggesting an interaction between background genetics and phenotype (Caberlotto et al 2007).…”

Epigenetics of Personality Traits: An Illustrative Study of Identical Twins Discordant for Risk-Taking Behavior

“…DLX1 expression is critical for NPY production, as DLX1 knockout mice show a progressive loss of NPY most likely as a result of interneuronal loss (Cobos et al, 2005). Numerous animal model studies implicate NPY in modulating stress and anxiety, as both NYP receptor antagonists and knockouts produce an anxiolytic effect (Bacchi et al, 2006). This is likely because the stress response produced by the HPA is inhibited by GABA (Kovacs et al, 2004); however, NPY release in turn inhibits the effects of GABA, effectively exciting stress response (Kash & Winder, 2006).…”