Role of 5-HT 1A receptors in the lower brainstem on the cardiovascular response to dorsomedial hypothalamus activation

Abstract

The dorsomedial hypothalamus (DMH) is an essential brain region for the integration of the physiological response to psychological stressors. The cardiovascular components of the response include increases in blood pressure, heart rate and the activity of sympathetic nerves to the kidney, skin, brown adipose tissue, and heart. Neurons in the rostral ventrolateral medulla (RVLM) and in the region of the medullary raphe are important components of the descending pathways that mediate the cardiovascular response to the DMH activation. Activation of 5-hydroxytryptamine 1A (5-HT 1A) receptors in the brain leads to a suppression of the cardiac and sympathetic vasomotor components of the DMH-evoked response and of the response to acute psychological stress. In this study we showed that intracisternal injection of a low dose (1 µg/kg) of the 5-HT 1A receptor agonist, 8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT), significantly reduced the increases in heart rate and renal sympathetic nerve activity evoked by disinhibition of the DMH, but had no effect on these responses when injected intravenously. Subsequent intracisternal administration of the 5-HT 1A receptor antagonist WAY-100635 restored the DMH-evoked cardiovascular responses to levels observed before 8-OH-DPAT administration. Bilateral microinjections of 8-OH-DPAT (200pmol on each side) into the RVLM, however, did not significantly affect the cardiovascular response to disinhibition of the DMH. These observations demonstrate that activation of 5-HT 1A receptors within the lower brainstem, but not in the RVLM, can powerfully suppress the cardiovascular response evoked from the DMH.