Neonatal maternal separation decreases mean arterial blood pressure in adult female rats

Abstract

Introduction The prevalence of depression is higher in adult women than in men. Interestingly, a decrease in arterial blood pressure is commonly observed in patients affected by this mood disorder. This association raises the possibility that low blood pressure could distinguish a subgroup of the population that are at higher risk to develop this psychiatric disorder. In rats, exposure to neonatal maternal separation (NMS) leads to depressive-like behaviors in adult animals, thus offering a simple translational model for pre-clinic studies. In addition, a variety of studies showed that during the premenstrual period a high number of women at reproductive-age present symptoms of irritability, emotional hypersensitivity, increased anxiety as well as depression. The impact of hormonal fluctuations on psychiatric disorders is well established, yet there are only a few studies regarding blood pressure control during different phases of the menstrual cycle. While the link between stress (including NMS) and hypertension has been well documented in males, the effects of hormonal fluctuations in pre-clinical studies in female animals have not been explored. Based on that, we developed two main hypotheses: 1) by comparison with undisturbed (control) rats, NMS decreases arterial blood pressure in adult females. 2) NMS will increase the impact of the estrous cycle on blood pressure. Methodology Rat pups were either undisturbed (control) or subjected to NMS during which pups were placed in individual spaces into a temperature-controlled incubator 3h/day from postnatal day 3 to 12. Once they reached adulthood, (8 weeks of age) cardiovascular parameters were measured in females using the tail cuff method. To cover all phases of the estrous cycle, we did our measurements once a week during 7 weeks, (between 8-14 weeks of animal's life), during the morning (9-12h) period. The data were analyzed using the two-way ANOVA test, comparing the treatment (CTRL vs NMS) and the phases of the estrous cycle. Results We showed that the diastolic and systolic pressures of NMS females were 5% less than controls (diastolic: CTRL: 84 mmHg, NMS: 79 mmHg, p=0.0015, systolic: CTRL: 121 mmHg, NMS: 116 mmHg, p=0.02). This resulted in a significant drop in mean arterial pressure (CTRL: 96 mmHg, NMS: 91 mmHg, p=0.02). The heart rate was similar between the groups. Surprisingly, we observed no effects of the estrous cycle on the blood pressure neither in NMS nor in control animals. Discussion This demonstrates that the NMS decreases the blood pressure of our female animals in adult life as observed in humans with anxiety and depressive behaviors. This observation further validates our model and justifies new studies exploring the mechanisms by which early life stress leads to physiological and psychiatric changes in adulthood. Ultimately, this research can help us develop more precise therapies for specific groups. For instance, Licht et al 2009 demonstrated that the use of antidepressant from patients that exhibited decreased blood pressure increases their risk to present hypertension.