ANXIOGENIC-LIKE EFFECT OF THE NPY Y-1 RECEPTOR ANTAGONIST BIBP3226 ADMINISTERED INTO THE DORSAL PERIAQUEDUCTAL GRAY-MATTER IN RATS

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 endog enous NPY in this and other brain areas has not been fully elucidated. The selective NPY Y-1 receptor antagonist (R)-N-2 nylacetyl)-N-[(4-hy droxy-phenyl)methyl]-D-arginine amide (BIBP3226) was microinjected int o various brain sites implicated in the regulation of anxiety-related behaviour and resultant behavioural changes were assessed using the el evated plus-maze (EPM) and open-field test in rats. Intracerebroventri cular application of BIBP3226 (5.0 mu g) which caused an anxiogenic-li ke effect in the EPM did not affect exploratory activity in the open-f ield test. A decrease in EPM exploration was observed also when BIBP32 26 (0.5 mu g) was microinjected into the dorsal periaqueductal gray ma tter (DPAG). Intra-DPAG BIBP3226 did not change open-field behaviour s uggesting that the effects of BIBP3226 in the EPM test were not relate d to changes in locomotor activity in general. Bilateral application o f BIBP3226 into the central nucleus of amygdala (0.5 and 2.5 mu g/side ) and unilateral injections into the locus coeruleus and the paraventr icular nucleus of the hypothalamus (both 0.5 mu g) were ineffective in modifying the plus-maze exploration. These data suggest that endogeno us NPY may regulate anxiety-related behaviour in rats by acting via th e NPY Y-1 receptors in DPAG. (C) 1998 Elsevier Science B.V. All rights reserved.