CHARACTERIZATION OF THE SYMPATHETIC-NERVE RESPONSES TO AMPHETAMINE - ROLE OF CENTRAL ALPHA(2)-ADRENERGIC RECEPTORS

Although amphetamine has profound cardiovascular actions, the role of the sympathetic nervous system in these responses is largely unknown. The purpose of this study was to characterize the sympathetic nerve re sponses to amphetamine and to determine whether these neural responses involve an action of amphetamine in the rostral ventrolateral medulla (RVLM). In sinoaortically denervated (SAD) and sham-SAD rats, ampheta mine dose-dependently increased mean arterial pressure (MAP) and heart rate (HR), while decreasing (-87 +/- 5%; max) renal sympathetic nerve discharge (SND) for 57 +/- 5 min. Comparison of the SND responses iu SAD and sham-SAD rats revealed a small but significant contribution of the baroreceptor reflex to the sympathoinhibitory response. In separa te studies, the bilateral microinjection of amphetamine into RVLM decr eased HX, MAP, and SND. The magnitude and duration of the decrease in SND elicited by amphetamine were significantly attenuated by the prior intravenous (i.v.) administration of idazoxan (alpha(2)-adrenergic an tagonist). The prior bilateral microinjection of idazoxan or piperoxan into RVLM significantly attenuated the duration of the sympathoinhibi tory responses elicited by i.v. amphetamine. Idazoxan and piperoxan al so tended to decrease the magnitude of the SND response; however, this reduction was significant at only the highest doses. The MAP and HR r esponses were unaffected by idazoxan treatment. The microinjection of terazosin (alpha(1)-adrenergic antagonist) or propranolol (beta-adrene rgic antagonist) into RVLM did not alter the HR, MAP, or SND responses to i.v. amphetamine. We conclude that i.v. amphetamine decreases SND in anesthetized rats, in large part, by a mechanism involving the acti vation of alpha(2)-adrenergic receptors in RVLM.