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Effects of gastrin-releasing peptide agonist and antagonist administered to the basolateral nucleus of the amygdala on conditioned fear in the rat

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Abstract

Rationale

Bombesin (BB)-like peptides have been shown to affect neuroendocrine and neural functions related to the stress response and the modulation of conditioned fear. In line with this view, central administration of gastrin-releasing peptide (GRP; a mammalian analogue of BB) or its receptor antagonist (D-Tpi6, Leu13 psi[CH2NH]-Leu14) BB(6–14) (RC-3095) modulates conditioned fear.

Objective

The present study examined the effects of bilateral infusions of GRP or its receptor antagonist (RC-3095) into the basolateral nucleus of the amygdala (BLA) on the conditioned emotional response.

Methods

The effects of GRP (150, 300, and 600 ng/0.5 μl) and/or RC-3095 (50, 500, and 1,000 ng/0.5 μl) on contextual and cued fear conditioning were assessed following direct bilateral infusion of these compounds into the BLA.

Results

Both GRP and RC-3095 (all doses) reduced freezing during the contextual testing period but did not influence responding in the cued test. Although both compounds reduced freezing in the contextual paradigms, at a moderate dose pretreatment with RC-3095 attenuated the GRP-elicited decrease in contextual freezing.

Conclusions

It appears that manipulation of GRP at the BLA may influence the expression of learned fear and that these effects preferentially influence contextual versus cue-dependent emotional responses.

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Acknowledgements

This study was supported by funds from the Canadian Institutes of Health Research (CIHR) and the Natural Science and Engineering Research Council of Canada (NSERC). HA is a Canada Research Chair in Neuroscience. All experiments were conducted in accordance with the Canadian Council of Animal Care and were approved by the animal care committee of the University of Ottawa.

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Authors and Affiliations

  1. School of Psychology, University of Ottawa, Ottawa, Ontario, Canada

    Christine Mountney & Zul Merali

  2. Department of Cellular & Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada

    Zul Merali

  3. University of Ottawa Institute of Mental Health Research, Ottawa, Ontario, K1N 6N5, Canada

    Zul Merali

  4. Institute of Neuroscience, Carleton University, Ottawa, Ontario, K1S 5B6, Canada

    Hymie Anisman

  5. University of Ottawa Institute of Mental Health Research, 1145 Carling Avenue Rm. 2054 Lady Grey Building, Ottawa, Ontario, K1Z 7K4, Canada

    Zul Merali

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  1. Christine Mountney
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Correspondence to Zul Merali.

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Mountney, C., Anisman, H. & Merali, Z. Effects of gastrin-releasing peptide agonist and antagonist administered to the basolateral nucleus of the amygdala on conditioned fear in the rat. Psychopharmacology 200, 51–58 (2008). https://doi.org/10.1007/s00213-008-1118-7

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