Maternal separation enhances neuronal activation and cardiovascular responses to acute stress in borderline hypertensive rats

Abstract

There is much evidence suggesting early life events, such has handling or repeated separations from the nest, can have a long-term effect on the biological and behavioral development of rats. The current study examined the effect of repeated maternal separation (MS) on the behavioral, cardiovascular, and neurobiological responses to stress in subjects vulnerable to environmental stressors as adults. Borderline hypertensive rats (BHR), which are the first generation offspring of spontaneously hyperternsive and Wistar-Kyoto rats, were separated from the dams for 3h per day from postnatal day 1 through 14. Non-separated controls remained in the home cage. When allowed to explore the open field chamber for 60 min as adults, MS subjects had significantly greater locomotor activity compared to controls. All subjects were exposed to 30 min of restraint stress during which time mean arterial pressure (MAP) and heart rate (HR) were measured. Although both groups had comparable increases in MAP, MS animals displayed significantly higher HR throughout the stress period. Finally, MS subjects had significantly more stress-induced Fos positive cells, an estimate of neuronal activation, in the central nucleus of the amygdala (CeA), paraventricular nucleus of the hypothalamus (PVN), and the bed nucleus of the stria terminalis (BNST), each of which plays an important role in organizing the biobehavioral response to stress. These results suggest that maternal separation can further enhance stress reactivity in this model and may represent a useful approach for studying the relationship between early life events and future vulnerability to stressful situations.

Figure 1

Total exploratory activity in open field (top panel) during 60 min test and binned in 10 minute blocks (bottom panel) for MS (n= 9) and N-MS (n=19) subjects. Data are expressed as mean ± SEM.

Figure 2

HR (top panel) and MAP (bottom panel) during 30 minutes of restraint stress in MS (n=14, open circle) and N-MS (n=10, closed squares) BHR. Data are expressed as mean ±SEM.

Figure 3

Fos immunoreactive cells in PVN (top panel), CeA (middle panel), and BST (bottom panel) in MS and N-MS BHR (n = 9−14 per group). Data are expressed as the mean±SEM.