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  Impaired extinction of learned fear in rats selectively bred for high anxiety - evidence of altered neuronal processing in prefrontal-amygdala pathways

Muigg, P., Hetzenauer, A., Hauer, G., Hauschild, M., Gaburro, S., Frank, E., et al. (2008). Impaired extinction of learned fear in rats selectively bred for high anxiety - evidence of altered neuronal processing in prefrontal-amygdala pathways. European Journal of Neuroscience, 28(11), 2299-2309.

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Genre: Journal Article
Alternative Title : Eur. J. Neurosci.

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 Creators:
Muigg, P., Author
Hetzenauer, A., Author
Hauer, G., Author
Hauschild, M., Author
Gaburro, S., Author
Frank, E.1, Author           
Landgraf, R.1, Author           
Singewald, N., Author
Affiliations:
1AG Landgraf, Rainer, Florian Holsboer (Direktor), Max Planck Institute of Psychiatry, Max Planck Society, ou_1607151              

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Free keywords: amygdala; c-Fos; cued fear conditioning; HAB; medial prefrontal cortex
 Abstract: 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.

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Language(s): eng - English
 Dates: 2008-12
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 396558
ISI: 000261184800014
 Degree: -

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Title: European Journal of Neuroscience
  Alternative Title : Eur. J. Neurosci.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 28 (11) Sequence Number: - Start / End Page: 2299 - 2309 Identifier: ISSN: 0953-816X