Anxiogenesis induced by social defeat in male mice: Role of nitric oxide, NMDA, and CRF1 receptors in the medial prefrontal cortex and BNST

Autor(es)

Faria, M. P. ^{[1, 2]} ; Laverde, C. F. ^{[1, 2]} ; Nunes-de-Souza, R. L. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] UNESP, Joint Grad Program Physiol Sci PIPGCF UFSCar, BR-14800903 Araraquara, SP - Brazil

^[2] Sao Paulo State Univ, Sch Pharmaceut Sci, Lab Pharmacol, UNESP, Araraquara, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Neuropharmacology; v. 166, APR 2020.
• Citações Web of Science: 0

Resumo

Nitric oxide (NO) release in the right medial prefrontal cortex (RmPFC) produces anxiogenesis. In the bed nucleus of the stria terminalis (BNST), a region that receives neuronal projections from the mPFC, NO provokes anxiety, an effect that is blocked by local injections of corticotrophin-releasing factor type 1 receptor (CRF1) or n-methyl-D-aspartate receptor (NMDAr) antagonist. Anxiety is also enhanced by social defeat stress, and chronic stress impairs and facilitates, respectively, PFC and BNST roles in modulating behavioral responses to aversive situations. This study investigated whether the (i) chronic social defeat stress (CSDS) increases NO signaling in the mPFC; and/or (ii) anxiogenic effects provoked by the intra-RmPFC injection of NOC-9 (an NO donor) or by CSDS are prevented by intra-BNST injections of AP-7 (0.05 nmol) or CP 376395 (3.0 nmol), respectively, NMDAr and CRF1 antagonists, in male Swiss-Webster mice exposed to the elevated plus-maze (EPM). Results showed that (a) CSDS increased anxiety (i.e., reduced open-arm exploration) and repeatedly activated nNOS-containing neurons, as measured by Delta FosB (a stable nonspecific marker of neural activity) + nNOS double-labeling, in the right (but not left) mPFC, (b) NOC-9 in the RmPFC also increased anxiety, and (c) both CSDS and NOC-9 effects were reversed by injections of AP-7 or CP 376395 into the BNST. These results suggest that NMDA and CRF1 receptors located in BNST play an important role in the modulation of anxiety provoked by NO in the RmPFC, as well as by chronic social defeat in mice. (AU)

• Processo FAPESP: 17/25409-0 - Mecanismos neurobiológicos subjacentes à lateralidade funcional do córtex pré-frontal medial nas reações de defesa induzidas pelo estresse de derrota social em camundongos
• Beneficiário: Ricardo Luiz Nunes de Souza
• Modalidade de apoio: Auxílio à Pesquisa - Regular