Role of gastrin-releasing peptide and neuromedin B in anxiety and fear-related behavior

Bombesin (BB)-like peptides have been implicated in the mediation and/or modulation of the stress response. However, the impact of manipulating this peptidergic system has only been assessed in a limited number of anxiety and fear paradigms. Given that different behavioral paradigms reflect different aspects of anxiety, the objective of the present investigation was to assess the effects of two mammalian BB-related peptides, namely gastrin-releasing peptide (GRP) and neuromedin B (NMB), in paradigms thought to reflect fear and anxiety-related behaviors. To this end, the effects of central (3rd ventricular; i.c.v.) administration of GRP (0.30 nmol), GRP receptor (BB2) antagonist, [Leu13-(CH2NH)Leu14]-BN (1.26 nmol), NMB-30 (0.29 nmol), NMB (BB1) receptor antagonist, BIM 23127 (1.70 nmol) and a mixed BB1/BB2 receptor antagonist, PD 176252 (0.621 nmol) were assessed in the elevated plus maze (EPM) and in a fear potentiated startle paradigm (a model thought to reflect conditioned fear). The BB1 receptor antagonist and the mixed BB1/BB2 receptor antagonist elicited anxiolytic effects in the EPM, whereas, the BB2 receptor antagonist was without effect. In the fear potentiated startle paradigm, pretreatment with either the BB1 receptor antagonist or the BB2 receptor agonist attenuated the fear potentiated startle response, without affecting basal startle amplitude. These data suggest that NMB and GRP do affect the stress response. However, whereas NMB manipulations affected both anxiety and fear responses, GRP alterations selectively affected fear-related responses.