When administered intravenously,
serotonin (
5-hydroxytryptamine; 5-HT) evokes a triphasic blood pressure response, consisting of the Bezold-Jarisch-associated depressor response, a pressor action, and long-lasting depressor response. Because the pressor response may, in part, be caused by central nervous system (CNS) activation by
5-HT, we predicted that destruction of the anteroventral third ventricle (AV3V) region, an area rich in
5-HT receptors, would attenuate increases in blood pressure to intravenous
5-HT. In anesthetized
sham-lesioned and AV3V-lesioned Sprague-Dawley rats, we measured mean arterial pressure (MAP), heart rate (HR), and lumbar sympathetic nerve activity (SNA) to increasing bolus doses of intravenous
5-HT (1, 2.5, 5, 10, 25 mu g/kg), before and after blockade of
bradycardia using
methylatropine (200 mu g/kg). In all rats, bolus
injections of
5-HT elicited
bradycardia accompanied by a fall in lumbar SNA and an initial
hypotension followed by a pressor response and a longer lasting hypotensive response. The
bradycardia, reduction in lumbar SNA, and both depressor responses were equivalent in
sham-lesioned and AV3V-lesioned groups. Importantly, AV3V lesions attenuated pressor responses to increasing doses of
5-HT (3 +/- 1, 6 +/- 4, 6 +/- 4, 17 -/+ 4 35 +/- 3 mmHg) compared to
sham-lesioned controls (6 +/- 3, 16 +/- 7, 33 +/- 5, 54 +/- 4, 51 +/- 6 mmHg; P < 0.0001). This attenuation was conserved following blockade of
bradycardia with
methylatropine (P < 0.01). In summary, pressor responses to intravenous
5-HT are diminished by AV3V lesions. These data indicate that the pressor component of the blood pressure response to intravenous
5-HT is partly dependent upon interaction with the CNS.