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Volume 17, Number 12, Issue of June 15, 1997 pp. 4895-4903
Copyright ©1997 Society for Neuroscience

Chronic Social Stress Alters Levels of Corticotropin-Releasing Factor and Arginine Vasopressin mRNA in Rat Brain

Received Aug. 21, 1996; revised April 2, 1997; accepted April 8, 1997.

David S. Albeck⁴, Christina R. McKittrick¹, D. Caroline Blanchard², Robert J. Blanchard², Julia Nikulina², Bruce S. McEwen¹, and Randall R. Sakai³

¹ Rockefeller University, New York, New York 10021, ² University of Hawaii, Honolulu, Hawaii 96822, ³  University of Pennsylvania, Philadelphia, Pennsylvania 19104, and ⁴ University of Colorado Health Sciences Center, Denver, Colorado 80262

In the visible burrow system model of chronic social stress, male rats housed in mixed-sex groups quickly form a dominance hierarchy in which the subordinates appear to be severely stressed. A subgroup of subordinates have an impaired corticosterone response after presentation of a novel restraint stressor, leading to their designation as nonresponsive subordinates. To examine the mechanism underlying the blunted corticosterone response in these animals, in situ hybridization histochemistry was used to quantify corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) mRNA expression in the brain. In two separate visible burrow system experiments, the nonresponsive subordinates expressed a significantly lower average number of CRF mRNA grains per cell in the paraventricular hypothalamic nucleus compared with stress-responsive subordinates, dominants (DOM), or cage-housed control (CON) rats. The number of CRF mRNA labeled cells was also significantly lower in nonresponders than in responsive subordinates or DOM. In the central amygdala, CRF mRNA levels were increased in both groups of subordinates compared with CON rats, whereas responsive subordinates exhibited higher levels than the DOM rats as well. AVP mRNA levels did not vary with behavioral rank in any subdivision of the paraventricular hypothalamic nucleus. In the medial amygdala, the number of cells expressing AVP mRNA was significantly greater in CON rats compared with both groups of subordinates, although the average number of AVP mRNA grains per cell did not vary with rank. In addition, the number of AVP-positive cells significantly correlated with plasma testosterone level.

Key words: stress; corticosterone; CRF; AVP; in situ hybridization; neuropeptide

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