Neonatal handling increases cardiovascular reactivity to contextual fear conditioning in borderline hypertensive rats (BHR)

Abstract

Much research has demonstrated that events occurring in early life can have a profound influence on future biobehavioral responses to stressful and emotion provoking situations. The purpose of these studies was to determine the effects of an early environmental manipulation, handling (HAN) on cardiovascular (CV) reactivity, freezing behavior and corticosterone (CORT) responses to contextual fear conditioning in the borderline hypertensive rat (BHR),which is susceptible to environmental stressors. HAN subjects were separated from the nest for 15 min/day on post-natal days 1-14, while non-handled (NON-HAN) controls remained in the home cage. Adult subjects were exposed to the contextual fear conditioning procedure and returned to the chamber 24 h later for a 10 min test period. HAN subjects displayed significantly more freezing behavior compared to NON-HAN(92%+/-2.2 vs 80.7%+/-5.7, p<.05). Although resting MAP did not differ between groups, HAN subjects had increased MAP reactivity when re-exposed to the chamber. In addition, HAN subjects had significantly lower CORT levels at the end of the 10 min test period (174.2+/-9 ng/ml vs 237.2+/-12.9 ng/ml, p<.05). In the second experiment, CORT responses to 60 min of restraint stress and recovery following return to the home cage were assessed in separate groups of HAN and NON-HAN subjects. HAN subjects showed reduced CORT levels in response to acute restraint stress. These results indicate that neonatal handling can modulate biobehavioral responses to contextual fear conditioning in BHR and may suggest a useful model with which to study emotionality and susceptibility to CV disease.

Figure 1

Change in MAP (top panel) and HR (bottom panel) in response to reexposure to the fear conditioning chamber in handled (dark squares, n=9) and non-handled (open circles, n=7) subjects. Data are expressed as mean ± SEM.

Figure 2

Plamsa corticosterone levels 10 minutes following re-exposure to the fear conditioning chamber in handled (shaded bar, n = 7) and non-handled (open bar, n = 5) subjects. Data are expressed as mean ± SEM.

Figure 3

Plasma corticosterone levels taken during a baseline period (time = 0), twice during 60 minutes of restraint stress (time = 30 and 60), and twice after return to the home cage (time = 90 and 120) in handled (dark squares, n = 7) and non-handled (open circles, n = 5) subjects. Data are expressed as mean ± SEM.

Figure 4

Freezing behavior during 10 min of response to re-exposure to the fear conditioning chamber in handled (shaded bar, n = 16 ) and non-handled (open bar, n = 13) subjects. Data are mean ± SEM.