Social isolation disrupts autonomic regulation of the heart and influences negative affective behaviors

Abstract

Background: There is a documented association between affective disorders (e.g., depression and anxiety) and cardiovascular disease in humans. Chronic social stressors may play a mechanistic role in the development of behavioral and cardiac dysregulation. The current study investigated behavioral, cardiac, and autonomic responses to a chronic social stressor in prairie voles, a rodent species that displays social behaviors similar to humans.

Methods: Female prairie voles were exposed to 4 weeks of social isolation (n = 8) or pairing (control conditions; n = 7). Electrocardiographic parameters were recorded continuously during isolation, and behavioral tests were conducted during and following this period.

Results: Isolation induced a significant increase in resting heart rate, reduction in heart rate variability (standard deviation of normal-to-normal intervals and amplitude of respiratory sinus arrhythmia), and exaggerated cardiac responses during an acute resident-intruder paradigm. Isolation led also to both depression-like and anxiety-like behaviors in validated operational tests. These changes in response to social isolation showed predictable interrelations and were mediated by a disruption of autonomic balance including both sympathetic and parasympathetic (vagal) mechanisms.

Conclusions: These findings indicate that social isolation induces behavioral, cardiac, and autonomic alterations related to those seen after other stressors and which are relevant to cardiovascular disease and affective disorders. This model may provide insight into the mechanisms that underlie these co-occurring conditions.

Figure 1

Mean (+ SEM) heart rate (Panel A), standard deviation of normal-to-normal intervals (SDNN index; Panel B), and amplitude of respiratory sinus arrhythmia (Panel C) in prairie voles at baseline and following 2 and 4 weeks of social isolation or pairing. Note the scale differences among the 3 panels. *P<0.05 vs. respective paired value; ^#P<0.05 vs. respective baseline value.

Figure 2

Mean (+ SEM) absolute fluid intake (Panel A) and mean sucrose preference, relative to total fluid intake (Panel B), during a 1-hour fluid intake test in prairie voles at baseline and following 2 and 4 weeks of social isolation or pairing. For sucrose intake and sucrose preference: *P<0.05 vs. respective paired value; ^#P<0.05 vs. respective baseline value.

Figure 3

Mean (+ SEM) heart rate in prairie voles following 4 weeks of social isolation or pairing. *P<0.05 vs. respective paired value; ^#P<0.05 vs. respective value during the open arms.

Figure 4

Mean (+ SEM) heart rate during a 5-minute resident-intruder test (Panel A) and time to recovery of heart rate following the test (to within 1% of pre-test heart rate values; Panel B) in prairie voles following 4 weeks of social isolation or pairing. *P<0.05 vs. respective paired value.

Figure 5

Mean (+ SEM) absolute heart rate (Panel A) relative to pre-drug values, and change in heart rate from pre-drug values (Panel B), in prairie voles following 4 weeks of social isolation or pairing and during β-adrenergic receptor blockade with atenolol, cholinergic receptor blockade with atropine, and combined receptor blockade with both drugs. *P<0.05 vs. respective paired value.