title: Cortagine infused into the medial prefrontal cortex attenuates predator-induced defensive behaviors and Fos protein production in selective nuclei of the amygdala in male CD1 mice.
abstract: Corticotropin-releasing factor (CRF) plays an essential role in coordinating the autonomic, endocrine and behavioral responses to stressors. In this study, we investigated the role of CRF within the medial prefrontal cortex (mPFC) in modulating unconditioned defensive behaviors, by examining the effects of microinfusing cortagine a selective type-1 CRF receptor (CRF1) agonist, or acidic-astressin a preferential CRF1 antagonist, into the mPFC in male CD-1 mice exposed to a live predator (rat exposure test--RET). Cortagine microinfusions significantly reduced several indices of defense, including avoidance and freezing, suggesting a specific role for CRF1 within the infralimbic and prelimbic regions of the mPFC in modulating unconditioned behavioral responsivity to a predator. In contrast, microinfusions of acidic-astressin failed to alter defensive behaviors during predator exposure in the RET. Cortagine microinfusions also reduced Fos protein production in the medial, central and basomedial, but not basolateral subnuclei of the amygdala in mice exposed to the rat predatory threat stimulus. These results suggest that CRF1 activation within the mPFC attenuates predator-induced unconditioned anxiety-like defensive behaviors, likely via inhibition of specific amygdalar nuclei. Furthermore, the present findings suggest that the mPFC represents a unique neural region whereby activation of CRF1 produces behavioral effects that contrast with those elicited following systemic administration of CRF1 agonists.
authors.affiliation: Department of Psychology, University of Hawaii, Honolulu, HI, USA; Pacific Biomedical Research Center, University of Hawaii, Honolulu, HI, USA; Specialized Neuroscience Research Program, University of Hawaii, Honolulu, HI, USA. Electronic address: nathan.pentkowski@asu.edu.
authors.forename: Nathan S
authors.initials: NS
authors.lastname: Pentkowski
authors.forename: Philip
authors.initials: P
authors.lastname: Tovote
authors.forename: Arturo R
authors.initials: AR
authors.lastname: Zavala
authors.forename: Yoav
authors.initials: Y
authors.lastname: Litvin
authors.forename: D Caroline
authors.initials: DC
authors.lastname: Blanchard
authors.forename: Joachim
authors.initials: J
authors.lastname: Spiess
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Blanchard
mesh_terms: D000679:Amygdala / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004291:Dominance-Subordination; D004924:Escape Reaction / Q000187:drug effects*; D020387:Food Chain; D057967:Infusions, Intraventricular; D008297:Male; D051379:Mice; D016761:Oncogene Proteins v-fos / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*
chemical_list: D016761:Oncogene Proteins v-fos; D011993:Recombinant Fusion Proteins; C488590:cortagine; D003346:Corticotropin-Releasing Hormone
keywords: Anxiety; CRF; Corticotropin-releasing factor; Defense; Emotion; Fear; PFC