title: Dorsomedial hypothalamus CRF type 1 receptors selectively modulate inhibitory avoidance responses in the elevated T-maze.
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 μl, experiment 1) or with the CRFR1 antagonist antalarmin (25 ng/0.2 μl, 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 μl) and antalarmin (25 ng/0.2 μl) (experiment 3). All animals were tested in an open field, immediately after the ETM, for locomotor activity assessment. Results showed that 250 ng/0.2μl 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.
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, 11060-001 Santos, SP Brazil.
authors.forename: Mariana S C F
authors.initials: MS
authors.lastname: Silva
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, 11060-001 Santos, SP Brazil.
authors.forename: Bruno A
authors.initials: BA
authors.lastname: Pereira
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, 11060-001 Santos, SP Brazil.
authors.forename: Isabel C
authors.initials: IC
authors.lastname: Céspedes
authors.affiliation: Departamento de Psiquiatria e Psicologia Médica, Universidade Federal de São Paulo, 04038-020 São Paulo, SP, Brazil.
authors.forename: Juliana O G
authors.initials: JO
authors.lastname: Nascimento
authors.affiliation: Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-000, SP, Brazil.
authors.forename: Jackson C
authors.initials: JC
authors.lastname: Bittencourt
authors.affiliation: Departamento de Biociências, Universidade Federal de São Paulo, 11060-001 Santos, SP Brazil. Electronic address: milenabv@gmail.com.
authors.forename: Milena B
authors.initials: MB
authors.lastname: Viana
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D001362:Avoidance Learning / Q000187:drug effects*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004924:Escape Reaction / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D000099052:CRF Receptor, Type 1
chemical_list: D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone
keywords: Anxiety; CRF; Corticotropin-releasing factor; Dorsomedial hypothalamus; Elevated T-maze; Panic