CRF type 1 receptors of the medial amygdala modulate inhibitory avoidance responses in the elevated T-maze.
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 medial amygdala (MeA) in the modulation of anxiety and fear-related responses. Male Wistar rats were bilaterally administered into the MeA with CRF (125 and 250 ng/0.2μl, 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 CRF, in the two doses administered, 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 MeA exerts anxiogenic effects by activating type 1 receptors, which might be of relevance to the physiopathology of generalized anxiety disorder.
Departamento de Biociências, Universidade Federal de São Paulo, 11060-001, Santos, Brazil.
Jéssica E
JE
Vicentini
Departamento de Biociências, Universidade Federal de São Paulo, 11060-001, Santos, Brazil.
Isabel C
IC
Céspedes
Departamento de Psiquiatria e Psicologia Médica, Universidade Federal de São Paulo, 04038-020, São Paulo, Brazil.
Juliana O G
JO
Nascimento
Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, 05508-000, Brazil.
Jackson C
JC
Bittencourt
Departamento de Biociências, Universidade Federal de São Paulo, 11060-001, Santos, Brazil. Electronic address: mviana@unifesp.br.
Milena B
MB
Viana
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D066276:Corticomedial Nuclear Complex / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D007266:Inhibition, Psychological; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology*; D000099052:CRF Receptor, Type 1
D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone
Anxiety; CRF; Corticotropin-releasing factor; Elevated T-maze; Fear; Medial amygdala; Panic