The effect of long-term ovariectomy on midbrain stress systems in free ranging macaques.

Communication between the serotonin system and the CRF system plays a pivotal role in the mediation of stress and stress reactivity. CRF appears to be inhibitory of serotonin neurotransmission through the CRF receptor type 1 (CRF-R1). Serotonin neurons also detect the urocortins, which are thought to be anxiolytic. Components of the CRF system in the serotonergic dorsal raphe region were examined in macaques that were ovary-intact or ovariectomized for 3 years living in a relatively natural environment. Female Japanese macaques (Macaca fuscata) were ovariectomized or tubal-ligated (n=5/group) and returned to their natal troop for 3 years. Quantitation of (1) CRF innervation of the serotonergic dorsal raphe, (2) CRF-Receptor type 1 (CRF-R1) in the dorsal raphe, (3) Urocortin 1 (UCN1) cells near the Edinger-Westfal nucleus and (4) UCN1 axons, was obtained with immunocytochemical staining and image analysis. There was no statistical difference in CRF axonal staining in the dorsal raphe, or in UCN1 axonal staining near the dorsal raphe. However, the average number of detectable UCN1 postive cells was significantly lower in the Ovx group than in the Intact group (p=0.003). Average CRF-R1 positive pixel number and positive cell number were significantly higher in the Ovx group than in the Intact group (p=0.005 and 0.02, respectivly). The higher expression of CRF-R1 and lower expression of UCN1 in the Ovx group indicates they may be more vulnerable to stress. The greater expression of CRF-R1 could cause a greater inhibition of serotonin upon a stress-induced increase in CRF as well.