Impaired serotonergic control of HR in depression Impaired serotonergic regulation of heart rate may underlie reduced baroreflex sensitivity in an animal model of depression

Serotonin (5HT) is crucial to normal reflex vagal modulation of heart rate (HR). Reduced baroreflex sensitivity (sBRS) and HR variability (HRV) reflect impaired neural, particularly vagal, control of HR and are independently associated with depression. In conscious, telemetered Flinders-Sensitive Line rats (FSL), a well-validated animal model of depression, we tested the hypothesis that cardiovascular regulatory abnormalities are present and associated with deficient serotonergic control of reflex cardio-vagal function. In FSL, and control Flinders-Resistant rat (FRL) and Sprague Dawley rat (SD) strains, diurnal measurements of HR, arterial pressure (AP), activity, sBRS and HRV were made. All strains had normal and similar diurnal variations in HR, AP and activity. HR was elevated in FRL contributing to the reduced HRV and sBRS seen in this strain. FSL had reduced sBRS and high frequency power HRV during the night indicating reduced reflex cardio-vagal activity. The ratio of low to high frequency bands of HRV was increased in FSL suggesting a relative predominance of cardiac sympathetic and/or reflex activity compared to FRL and SD. These data show that conscious FSL have cardiovascular regulatory abnormalities similar to depressed humans. Acute changes in HR, AP, temperature and sBRS to 8-OHDPAT, 5HT-1A/1B/7 receptor agonist, were also determined. In FSL, despite inducing an exaggerated hypothermic effect, 8-OHDPAT did not decrease HR and AP or improve sBRS suggesting impaired serotonergic neural control of cardio-vagal activity. These data suggest that impaired serotonergic control of cardiac reflex function could be one mechanism linking reduced sBRS to increased cardiac risk in depression.