title: Effects of dorsal periaqueductal gray CRF1- and CRF2-receptor stimulation in animal models of panic.
abstract: An increasing amount of evidence suggests that dysregulation of corticotrophin-releasing factor (CRF) signaling may contribute to the etiology of anxiety disorders such as post-traumatic stress disorder and panic. The dorsal periaqueductal gray matter (dPAG) in the midbrain has been considered a key region involved in the physiopathology of anxiety and panic. Administration of CRF in this structure enhances the expression of anxiety-related defensive behaviors in different animal models. Controversial results have been obtained regarding the involvement of CRF1 and CRF2 receptors in the regulation of panic-related responses. We report here that CRF (0.0625-1 μg) in the dPAG facilitates escape expression in two animal models that associate this behavior with panic, the elevated T-maze and the electrical stimulation of the dPAG. This effect, equally observed after CRF injection in the dorsomedial and dorsolateral columns of the PAG, is due to the activation of CRF1 receptors as revealed by its blockade by the CRF1 receptor antagonist antalarmin. In the elevated T-maze, CRF also facilitates inhibitory avoidance acquisition, suggesting an anxiogenic effect. Local administration of urocortin 2 (0.01-0.1 μg), a preferential CRF2 receptor agonist, failed to change escape expression, but impaired avoidance learning, indicating an anxiolytic effect. The results indicate that CRF1 receptors in the dPAG play a pervasive role in the regulation of defensive responses associated with both generalized anxiety and panic. Recruitment of CRF2 receptors only impacts upon the former type of behaviors, leading to an effect opposed to that caused by CRF1 receptor activation.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Thatiane de Oliveira
authors.initials: Tde O
authors.lastname: Sergio
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Ailton
authors.initials: A
authors.lastname: Spiacci
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, São Paulo, Brazil. Electronic address: zangross@fmrp.usp.br.
authors.forename: Hélio
authors.initials: H
authors.lastname: Zangrossi
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D008297:Male; D008845:Microinjections; D010200:Panic / Q000187:drug effects*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D054832:Urocortins / Q000008:administration & dosage / Q000494:pharmacology; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C103016:antalarmin; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone
keywords: Anxiety; CRF; Dorsal periaqueductal gray; Elevated T-maze; Escape; Inhibitory avoidance; Panic