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

• Published in: Biological psychiatry (1969) Vol. 55; no. 7; pp. 715 - 723
• Main Authors: Salomé, Nicolas, Salchner, Peter, Viltart, Odile, Sequeira, Henrique, Wigger, Alexandra, Landgraf, Rainer, Singewald, Nicolas
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2004; Elsevier Science; Elsevier
• Subjects: Adrenocorticotropic Hormone; Adrenocorticotropic Hormone - blood; Adult and adolescent clinical studies; Affectivity. Emotion; Animals; Anterior Hypothalamic Nucleus; Anterior Hypothalamic Nucleus - metabolism; Anxiety; Anxiety - genetics; Anxiety - psychology; Anxiety disorders. Neuroses; Arousal; Arousal - genetics; Biological and medical sciences; Brain; Brain - metabolism; Brain Mapping; elevated plus-maze; Fear; Fear - physiology; Fos mapping; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Expression - physiology; Gyrus Cinguli; Gyrus Cinguli - metabolism; HAB; Hippocampus; Hippocampus - metabolism; HPA axis; Hypothalamic Area, Lateral; Hypothalamic Area, Lateral - metabolism; Hypothalamo-Hypophyseal System; Hypothalamo-Hypophyseal System - metabolism; Immunoenzyme Techniques; LAB; Life Sciences; Male; Medical sciences; Miscellaneous; Nerve Net; Nerve Net - metabolism; Neurons; Neurons - metabolism; Neurons and Cognition; open field; Paraventricular Hypothalamic Nucleus; Paraventricular Hypothalamic Nucleus - metabolism; Personality. Affectivity; Phenotype; Preoptic Area; Preoptic Area - metabolism; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-fos - genetics; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Rats; Rats, Wistar; Selection (Genetics); Selection, Genetic; Thalamus; Thalamus - metabolism; Trait anxiety; elevated plus-maze; open field; Fos mapping; HAB; HPA axis; Trait anxiety; LAB; Affect affectivity; Animal model; Rat; Hypothalamohypophysoadrenal axis; Exploratory behavior; Rodentia; Experimental study; Gene expression; Open field behavior; Vertebrata; Breeding line; Mammalia; Animal; Anxiety; Comparative study
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2003.10.021

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