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bioRxiv · 10.1101/784488

Role of CRF receptor 1 antagonism in the bed nucleus of the stria terminalis of male rats after intermittent social defeat stress

Vasconcelos, M.·Stein, D.·Gallas-Lopes, M.·Landau, L.·Behrens, L.·Albrechet-Souza, L.·Miczek, K.·de Almeida, R. M. M.
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Abstract

We recently demonstrated that the experience of brief episodes of social defeat caused impairments in social behaviors. Moreover, we provided evidence that the antagonism of corticotropin-releasing factor binding protein (CRFBP) in the bed nucleus of the stria terminalis (BNST) restored social approach in stressed animals. This study aimed to test the relation between corticotropin-releasing factor receptor type 1 (CRFR1) located in the BNST and the establishment of social stress-disrupted behaviors in rats submitted to social defeat in the resident-intruder paradigm. Animals were tested for sweet solution preference, subjected to the elevated-plus maze (EPM), and to the social interaction three-chamber test. Social behavior was tested after BNST drug infusions. The drug used in this study was a CRF receptor 1 antagonist, CP376395 (CP), administered in two doses: 50 ng/0.20 L/side, and 500 ng/0.20 L/side. Saline solution was used as vehicle and administered 0.20 L/side. Socially stressed animals (n = 11) did not differ compared to control animals (n = 11) in the EPM. Stressed animals displayed impaired social behavior, represented by a decrease in time spent in the interaction zone. The lower dose (CP 50 ng/0.20 L/side) administered intra-BNST restored social behaviors in stressed animals. On the other hand, the higher dose of the CRFR1 antagonist (CP 500 ng/0.20 L/side) induced social avoidance in rats without a history of agonistic confrontations. These findings implicate BNST CRFR1 signaling in the modulation of social behaviors in rats given the choice to explore an unfamiliar conspecific.

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Vasconcelos, M., Stein, D., Gallas-Lopes, M., Landau, L., Behrens, L., Albrechet-Souza, L., Miczek, K., de Almeida, R. M. M.. 2019-10-09. Role of CRF receptor 1 antagonism in the bed nucleus of the stria terminalis of male rats after intermittent social defeat stress. https://doi.org/10.1101/784488

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