Ventrolateral medulla: an important site of action for the hypotensive effect of drugs that activate serotonin-1A receptors.

The purpose of our study was to test the hypothesis that drugs that activate the 5-HT1A receptor lower arterial pressure by interacting with 5-HT1A receptors located in the ventrolateral medulla. For this purpose, cats were anesthetized with alpha-chloralose while arterial pressure, heart rate, and several indices of respiratory activity were being monitored during either topical application or microinjection of 5-HT1A receptor agonist and antagonist drugs in the region of the intermediate area of the ventrolateral medulla. Topical application of drugs that activate 5-HT1A receptors (e.g., 8-OH-DPAT and urapidil) produced decreases in arterial pressure, heart rate, and tidal volume but an increase in respiratory rate. These effects were prevented by prior topical application of the 5-HT1A antagonist drug, spiperone. Intravenous administration of 5-HT1A receptor agonist drugs produced similar cardiorespiratory effects, and these effects were counteracted by topical application of spiperone to the intermediate area of the ventrolateral medulla. Microinjection of 8-OH-DPAT into two sites associated with the intermediate area, namely the subretrofacial nucleus and the bicuculline-sensitive hypotensive site, also resulted in decreases in arterial pressure (-40 +/- 10 mm Hg, n = 5; and -21 +/- 4 mm Hg, n = 3, respectively). These data indicate that hypotension produced by drugs that activate 5-HT1A receptors occurs, at least in part, from an action in the ventrolateral medulla, presumably in the subretrofacial nucleus and/or the bicuculline-sensitive hypotensive site.