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          Institute: MPI für Psychiatrie     Collection: Publikationen MPI für Psychiatrie     Display Documents

ID: 396558.0, MPI für Psychiatrie / Publikationen MPI für Psychiatrie
Impaired extinction of learned fear in rats selectively bred for high anxiety - evidence of altered neuronal processing in prefrontal-amygdala pathways
Authors:Muigg, P.; Hetzenauer, A.; Hauer, G.; Hauschild, M.; Gaburro, S.; Frank, E.; Landgraf, R.; Singewald, N.
Date of Publication (YYYY-MM-DD):2008-12
Title of Journal:European Journal of Neuroscience
Journal Abbrev.:Eur. J. Neurosci.
Issue / Number:11
Start Page:2299
End Page:2309
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:The impaired extinction of acquired fear is a core symptom of anxiety disorders, such as post-traumatic stress disorder, phobias or panic disorder, and is known to be particularly resistant to existing pharmacotherapy. We provide here evidence that a similar relationship between trait anxiety and resistance to extinction of fear memory can be mimicked in a psychopathologic animal model. Wistar rat lines selectively bred for high (HAB) or low (LAB) anxiety-related behaviour were tested in a classical cued fear conditioning task utilizing freezing responses as a measure of fear. Fear acquisition was similar in both lines. In the extinction trial, however, HAB rats showed a marked deficit in the attenuation of freezing responses to repeated auditory conditioned stimulus presentations as compared with LAB rats, which exhibited rapid extinction. To gain information concerning the putatively altered neuronal processing associated with the differential behavioural response between HAB and LAB rats, c-Fos expression was investigated in the main prefrontal-amygdala pathways important for cued fear extinction. HAB compared to LAB rats showed an attenuated c-Fos response to repeated conditioned stimulus presentations in infralimbic and cingulate cortices, as well as in the lateral amygdala, but facilitated the c-Fos response in the medial part of the central amygdala. In conclusion, the present results support the notion that impaired extinction in high anxiety rats is accompanied by an aberrant activation profile in extinction-relevant prefrontal-amygdala circuits. Thus, HAB rats may represent a clinically relevant model to study the mechanisms and potential targets to accelerate delayed extinction processes in subjects with enhanced trait anxiety.
Free Keywords:amygdala; c-Fos; cued fear conditioning; HAB; medial prefrontal cortex
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:N. N.
Affiliations:MPI für Psychiatrie
External Affiliations:[Muigg, Patrik; Hetzenauer, Alfred; Hauer, Gabriele; Hauschild, Markus; Gaburro, Stefano; Singewald, Nicolas] Innsbruck Univ, Ctr Mol Biosci Innsbruck, Dept Pharmacol & Toxicol, Inst Pharm, A-6020 Innsbruck, Austria.; [Frank, Elisabeth; Landgraf, Rainer] Max Planck Inst Psychiat, Dept Behav Neuroendocrinol, D-8000 Munich, Germany.
Identifiers:ISI:000261184800014 [ID No:1]
ISSN:0953-816X [ID No:2]
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