The effect of short moderate stress on the midbrain corticotrophin releasing factor system in a macaque model of functional hypothalamic amenorrhea

FHA-type stress reverses the relative difference in CRF innervation of the serotonergic raphe nucleus between stress-sensitive and stress-resilient animals, and may decrease urocortin 1 transport from cells to axons.

Cynthia L. Bethea, Ph.D., Kenny Phu, B.S., Arubala P. Reddy, Ph.D., Judy L. Cameron, Ph.D.

Volume 100, Issue 4, Pages 1111-1121.e2, October 2013


To study the effect of moderate stress on corticotropin-releasing factor (CRF) components in the serotonergic midbrain region in a monkey model of functional hypothalamic amenorrhea.

After characterization of stress sensitivity, monkeys were moved to a novel room and given 20% less chow for 5 days before euthanasia.

Primate research center.

Female cynomolgus macaques (Macaca fascicularis) characterized as highly stress resilient (HSR, n = 5), medium stress resilient (n = 4), or stress sensitive (SS, n = 4).

Five days of diet in a novel room with unfamiliar conspecifics.

Main Outcome Measure(s):
Density of CRF axons in the serotonergic dorsal raphe nucleus; the number of urocortin 1 (UCN1) cells; the density of UCN1 axons; the expression of CRF receptor 1 (CRF-R1) and CRF-R2 in the dorsal raphe nucleus.

The CRF innervation was higher in HSR than in SS animals; UCN1 cell number was higher in HSR than in SS animals and UCN1 axon bouton density was not different; all opposite of nonstressed animals. The CRF-R1 was not different between the sensitivity groups, but CRF-R2 was higher in HSR than in SS animals. The relative expression of CRF-R1 and CRF-R2 was similar to nonstressed animals.

The HSR animals respond to stress with an increase in CRF delivery to serotonin neurons. With stress, UCN1 transport decreases in HSR animals. The CRF receptor expression was similar with or without stress. These changes may contribute to resilience in HSR animals.

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