Further evidence that extracellular serotonin in the rostral ventrolateral medulla modulates 5-HT1A receptor-mediated attenuation of exercise pressor reflex

We determined changes in extracellular levels of glutamate, serotonin (5-HT), norepinephrine (NE), and dopamine (DA) within rostral ventrolateral medulla (RVLM) during 5-HT_1A-receptor stimulation-mediated inhibition of cardiovascular responses to static muscle contraction using anesthetized rats. In ten rats, muscle contraction significantly increased (P<0.01) mean arterial pressure (MAP) by 29±4 mmHg, heart rate (HR) by 25±3 bpm, and glutamate levels by 4.5±0.8 ng/5 μl. Microdialysis of a 5-HT_1A receptor agonist, 8-OH-DPAT (10 mM), into the RVLM for 30 min attenuated cardiovascular responses to muscle contraction and had no effect on glutamate levels. A subsequent administration of 10 mM WAY100635, a 5-HT_1A antagonist, into the RVLM antagonized the attenuating effects of 8-OH-DPAT. In another ten rats, muscle contraction significantly increased (P<0.01) MAP and HR by 20±2 mmHg and 25±8 bpm, respectively. In addition, levels of 5-HT, NE, and DA in the RVLM significantly increased (P<0.01) by 3.6±0.3, 3.2±0.3, and 3.3±0.4 pg/10 μl, respectively. Administration of 8-OH-DPAT (10 mM) into the RVLM for 30 min attenuated cardiovascular responses to muscle contraction and had no effects on NE and DA levels. However, the drug significantly attenuated 5-HT levels following a muscle contraction. Microdialysis of 10 mM WAY100635 into the RVLM reversed both cardiovascular and 5-HT changes. These results suggest that stimulation of 5-HT_1A-receptors within the RVLM attenuates cardiovascular responses to static exercise via a reduction of extracellular 5-HT concentration and most likely not through changes in glutamate, NE or DA levels.