Early life stress causes sex-dependent disorders of cardiovascular regulation in adult rats

Abstract

Background. Early life stress (ELS) is caused by adverse and traumatic events in childhood and is associated with an increased risk of developing mental and physical disorders later in life.

The aim of the study was to investigate the effect of maternal separation and isolation from littermates (MSI) in early ontogenesis on the heart rate autonomic regulation in young adult rats of both sexes under physical (footshock, FS) and psychosocial emotional stress (EmS) (observation of a rat receiving FS, "witness stress").

Methods. Electrocardiograms were recorded noninvasively in non-anesthetized rats (subjected to MSI, 32 males and 28 females, or raised with mother, 23 males and 24 females) using a special cuff with attached electrodes. The heart rate (HR) and time-domain and spectral parameters of the heart rate variability (HRV) were quantified for each 5-min recording.

Results. In the control group, females showed increased basal HRV and HF-range power compared to males. In females (but not in males), after repeated (for 5 days) FS, an increase in HR and a decrease in HRV were observed; EmS caused a decrease in HR. Rats of both sexes after MSI developed a hyperactive phenotype, aggression, and decreased social interaction. Behavioral disorders were accompanied by an increase in basal HR and a decrease in HRV. In the MSI group, in response to repeated FS, HR increased only in females, while EmS caused an increase in HR in rats of both sexes. Moreover, after EmS, HRV increased in females but decreased in males.

Conclusion. ELS caused sex-dependent dysfunctions of the autonomic nervous system in adult rats. Autonomic dysregulation may be one of the mechanisms for stress vulnerability and stress-induced pathologies in adulthood.