Hypothalamic expression of serotonin 1A, 2A and 2C receptor and GAD67 mRNA in female cynomolgus monkeys with different sensitivity to stress.

Like women, female cynomolgus monkeys show differential sensitivity to stress-induced reproductive dysfunction. A combined social and metabolic stress (mild diet+moderate exercise+relocation) will rapidly induce anovulation in a third of female cynomolgus monkeys (stress-sensitive; SS); a third will ovulate once and then become anovulatory (medium stress-resilient; MSR) and a third are highly stress-resilient (HSR) and exhibit normal menstrual cycles through two stressed menstrual cycles. In a non-stressed menstrual cycle, SS animals have lower levels of estrogen and progesterone, lower activity of the serotonin system and lower expression of genes related to the serotonin system in the dorsal raphe nucleus. In this study, we examined the expression of 5HT1A, 5HT2A, 5HT2C receptors and GAD67 in the hypothalamus of SS, HSR and MSR monkeys using in situ hybridization. SS monkeys exhibited higher expression of 5HT2A mRNA in the paraventricular nucleus (PVN), higher expression of 5HT2C and GAD67 in the infundibulum, as well as higher expression of GAD67 in the posterior hypothalamus (PH), compared with HSR monkeys. However, the expression of 5HT1A mRNA in the ventromedial nucleus (VMN) was not different between groups. We speculate that the serotonin and GABA systems may be altered in the stress-response and reproductive-related circuits of SS monkeys, and may be participating in altering the sensitivity of the reproductive system to stress in these individuals.