Dorsomedial hypothalamus CRF type 1 receptors selectively modulate inhibitory avoidance responses in the elevated T-maze

Dorsomedial hypothalamus CRF type 1 receptors selectively modulate inhibitory avoidance responses in the elevated T-maze

Author Silva, Mariana Santos Carvalho de Faria Autor UNIFESP Google Scholar
Pereira, Bruno Aranha Autor UNIFESP Google Scholar
Céspedes, Isabel Cristina Autor UNIFESP Google Scholar
Nascimento, Juliana Olivetti Guzman Autor UNIFESP Google Scholar
Bittencourt, Jackson C. Google Scholar
Viana, Milena de Barros Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Abstract Corticotropin-releasing factor (CRF) plays a critical role in the mediation of physiological and behavioral responses to stressors. in the present study, we investigated the role played by the CRF system within the dorsomedial hypothalamus (DMH) in the modulation of anxiety- and panic-related responses. Male Wistar rats were administered into the DMH with CRF (125 and 250 ng/0.2 mu l, experiment 1) or with the CRFR1 antagonist antalarmin (25 ng/0.2 mu l, experiment 2) and 10 min later tested in the elevated T-maze (ETM) for inhibitory avoidance and escape measurements. in clinical terms, these responses have been respectively related to generalized anxiety and panic disorder. To further verify if the anxiogenic effects of CRF were mediated by CRFR1 activation, we also investigated the effects of the combined treatment with CRF (250 ng/0.2 mu l) and antalarmin (25 ng/0.2 mu l) (experiment 3). All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. Results showed that 250 ng/0.2 mu l of CRF facilitated ETM avoidance, an anxiogenic response. Antalarmin significantly decreased avoidance latencies, an anxiolytic effect, and was able to counteract the anxiogenic effects of CRF. None of the compounds administered altered escape responses or locomotor activity measurements. These results suggest that CRF in the DMH exerts anxiogenic effects by activating type 1 receptors, which might be of relevance to the physiopathology of generalized anxiety disorder. (C) 2014 Elsevier B.V. All rights reserved.
Keywords Corticotropin-releasing factor
Dorsomedial hypothalamus
Elevated T-maze
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Grant number FAPESP: 2011/17471-0
FAPESP: 2013/17389-8
Date 2014-09-01
Published in Behavioural Brain Research. Amsterdam: Elsevier B.V., v. 271, p. 249-257, 2014.
ISSN 0166-4328 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 249-257
Access rights Closed access
Type Article
Web of Science ID WOS:000340323000034

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