Neurobiological correlates of high (HAB) versus low anxiety-related behavior (LAB): differential Fos expression in HAB and LAB rats

doi:10.1016/j.biopsych.2003.10.021

Biological Psychiatry

Volume 55, Issue 7, 1 April 2004, Pages 715-723

https://doi.org/10.1016/j.biopsych.2003.10.021 Get rights and content

Abstract

Background

Two Wistar rat lines selectively bred for either high (HAB) or low (LAB) anxiety-related behavior were used to identify neurobiological correlates of trait anxiety.

Methods

We used Fos expression for mapping of neuronal activation patterns in response to mild anxiety-provoking challenges.

Results

In both lines, exposure to an open field (OF) or the open arm (OA) of an elevated plus-maze induced Fos expression in several brain areas of the anxiety/fear circuitry. Rats of the HAB type, which showed signs of a hyperanxious phenotype and a hyperreactive hypothalamic–pituitary–adrenal axis compared with LAB rats, exhibited a higher number of Fos-positive cells in the paraventricular nucleus of the hypothalamus, the lateral and anterior hypothalamic area, and the medial preoptic area in response to both OA and OF. Less Fos expression was induced in the cingulate cortex in HAB than in LAB rats. Differential Fos expression in response to either OA or OF was observed in few brain regions, including the thalamus and hippocampus.

Conclusions

The present data indicate that the divergent anxiety-related behavioral response of HAB versus LAB rats to OF and OA exposures is associated with differential neuronal activation in restricted parts of the anxiety/fear circuitry. Distinct hypothalamic regions displayed hyperexcitability, and the cingulate cortex showed hypoexcitability, which suggests that they are main candidate mediators of dysfunctional brain activation in pathologic anxiety.

Section snippets

Animals

All animals tested were bred in the animal facilities of the Max Planck Institute of Psychiatry in Munich, Germany, as described previously (for a review, see Landgraf and Wigger 2002). The rats used in the present study were adult male animals (300–400 g) from the F12 generation. They were housed in groups of 3–5 per cage under controlled conditions of temperature, light, and humidity, with free access to food and water. At least 24 hours before the experiment, animals were taken in their home

Line differences in behavioral and neuroendocrine measures

During OF exposure, the time spent in the central zone and the number of entries into the central zone of the arena were significantly lower in HAB than in LAB rats (Figure 2A, B). In this test, the total distance traveled was lower in HAB than in LAB rats (Figure 2C). Whereas basal levels of ACTH were not different between HAB and LAB rats, responses to OF were higher in the former (Figure 2D).

During OA exposure, the time spent in and the number of entries into the distal zone of the OA were

Discussion

This study demonstrates that the brain activity pattern evoked by mild anxiogenic stimuli differs in the HAB and LAB rat lines selectively bred for extremes in anxiety-related behavior. The most striking finding was that HAB rats, with a higher level of trait anxiety and HPA axis reactivity than LAB animals, exhibited enhanced Fos expression in the medial and lateral hypothalamus, whereas they displayed less activation in the medial prefrontal cortex in response to both OF and OA exposures.

Acknowledgements

This work was supported by Deutsche Forschungsgemeinschaft (AW, RL), an Austrian Science Foundation FWF research grant (NSi), and Région Nord-Pas de Calais (NSa, OV, HS).

We thank L. Brunet and G. Courtand for their technical assistance and Iris Neumayr for excellent animal care.

Nicolas Salomé and Peter Salchner contributed equally to this work.

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Original articleNeurobiological correlates of high (HAB) versus low anxiety-related behavior (LAB): differential Fos expression in HAB and LAB rats

Abstract

Background

Methods

Results

Conclusions

Section snippets

Animals

Line differences in behavioral and neuroendocrine measures

Discussion

Acknowledgements

Neuroscience

Brain Res Bull

Psychoneuroendocrinology

Biol Psychiatry

Neuroscience

Brain Res

Brain Res

Neurosci Biobehav Rev

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Eur J Pharmacol

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Neurosci Biobehav Rev

Neurochem Int

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Neuropsychopharmacology

Behav Brain Res

Neurosci Biobehav Rev

Brain Res

Behav Brain Res

Neurobiol Aging

Brain Res

Behav Brain Res

Brain Res

Neurosci Biobehav Rev

Biol Psychiatry

Behav Brain Res

Biol Psychiatry

Neuroscience

Physiol Behav

The anterior cingulate cortex. The evolution of an interface between emotion and cognition

Ann N Y Acad Sci

Conditioned fear-induced changes in behavior and in the expression of the immediate early gene c-fosWith and without diazepam pretreatment

J Neurosci

Original article
Neurobiological correlates of high (HAB) versus low anxiety-related behavior (LAB): differential Fos expression in HAB and LAB rats