The role of gastrin-releasing peptide on conditioned fear: Differential cortical and amygdaloid responses in the rat

Rationale: Bombesin (BB), an amphibian peptide, was shown to affect the expression of the stress response. However, the physiological role of the mammalian counterparts of BB in mediating anxiety and fear responses remain to be characterized. Objective: This study examined the effects of gastrin-releasing peptide (GRP), a mammalian analogue of BB, and its receptor antagonist, BW2258U89, on conditioned emotional response (CER), using fear conditioning. Materials and methods: The effects of these compounds on contextual and cued fear conditioning were assessed after direct bilateral infusions into the prelimbic (PrL) cortex, infralimbic (IL) cortex or central nucleus of the amygdala (CeA). Results: GRP (300 ng) microinjected into each of the three target nuclei significantly reduced freezing to contextual cues. Similarly, in the cued portion of CER, GRP administered to the IL cortex significantly reduced freezing. Administration of BW2258U89 resulted in dose-dependent and site-specific effects. At the IL cortex, the 50 ng dose decreased freezing to both contextual and cued fear conditioning. At the CeA, the 300 ng dose also decreased freezing, but at the 50 ng dose, it increased contextual freezing. At the PrL cortex, BW2258U89 did not affect freezing. Conclusions: These results illustrate that (1) GRP system(s) can significantly affect the expression of learned fear, (2) some of the relevant brain sites mediating these effects include the PrL, IL and the CeA, and (3) such effects may be dependent upon whether responses were evoked by environmental contextual fear cues or by specific auditory cues that were explicitly paired with an aversive stimulus.