Effects of chronic mild stress on GABAergic system in the paraventricular nucleus of hypothalamus associated with cardiac autonomic activity.

Stress is associated with cardiovascular diseases. One possible mechanism is the reduction in gamma-aminobutyric acid (GABA)ergic transmission at the paraventricular nucleus (PVN), which contributes to the disinhibition of sympathoexcitatory circuits and activates sympathetic outflow. At present, the mechanism of chronic mild stress (CMS) on GABAergic transmission at the PVN and cardiac autonomic activity is not yet fully clarified. Therefore, this study was designed to investigate the effects of CMS on the GABAergic system at the PVN and on the cardiac autonomic activity. Adult male Sprague-Dawley rats were randomly assigned to control (left undisturbed in their home cage) or CMS (subjected to various mild stressors for 4 weeks). Cardiac autonomic activities were determined by heart rate variability (HRV) analysis, and GABAergic alterations at the PVN were determined from GABA levels and mRNA expression of GABA-related activities. Results showed that the CMS group had decreased HRV as determined by the standard deviation of all R-R intervals (SDNN). The low frequency (LF) and high frequency (HF) powers of the CMS group were higher than those of the control. Hence, the LF/HF ratio was consequently unaffected. These findings indicated that despite the increase in sympathetic and parasympathetic activities, the autonomic balance was preserved at 4 weeks post CMS. For the GABAergic-related parameters, the CMS group had decreased mRNA expression of glutamic acid decarboxylase-65 (GAD-65), the GABA-synthesizing enzyme, and increased mRNA expression of gamma-aminobutyric acid transporter-1 (GAT-1). Moreover, the GAD-65 mRNA expression was negatively correlated with LF. In conclusion, 4-week CMS exposure in male rats could attenuate GABAergic transmission at the PVN and alter cardiac autonomic activities.