Anxiogenic-like effect of the NPY Y 1 receptor antagonist BIBP3226 administered into the dorsal periaqueductal gray matter in rats

Abstract

Exogenous neuropeptide Y (NPY) administered intracerebroventricularly or into the central nucleus of amygdala has anxiolytic-like effects in animal models of anxiety. These effects are probably mediated by the NPY Y 1 receptor. The role of the NPY Y 1 receptor activation by endogenous NPY in this and other brain areas has not been fully elucidated. The selective NPY Y 1 receptor antagonist (R)- N 2-(diphenylacetyl)- N-[(4-hydroxy-phenyl)methyl]- d-arginine amide (BIBP3226) was microinjected into various brain sites implicated in the regulation of anxiety-related behaviour and resultant behavioural changes were assessed using the elevated plus-maze (EPM) and open-field test in rats. Intracerebroventricular application of BIBP3226 (5.0 μg) which caused an anxiogenic-like effect in the EPM did not affect exploratory activity in the open-field test. A decrease in EPM exploration was observed also when BIBP3226 (0.5 μg) was microinjected into the dorsal periaqueductal gray matter (DPAG). Intra-DPAG BIBP3226 did not change open-field behaviour suggesting that the effects of BIBP3226 in the EPM test were not related to changes in locomotor activity in general. Bilateral application of BIBP3226 into the central nucleus of amygdala (0.5 and 2.5 μg/side) and unilateral injections into the locus coeruleus and the paraventricular nucleus of the hypothalamus (both 0.5 μg) were ineffective in modifying the plus-maze exploration. These data suggest that endogenous NPY may regulate anxiety-related behaviour in rats by acting via the NPY Y 1 receptors in DPAG.