TY - JOUR T1 - Clonidine Evokes Vasodepressor Responses via α<sub>2</sub>-Adrenergic Receptors in Gigantocellular Reticular Formation JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 688 LP - 694 VL - 289 IS - 2 AU - Sue A. Aicher AU - Carrie T. Drake Y1 - 1999/05/01 UR - http://jpet.aspetjournals.org/content/289/2/688.abstract N2 - The gigantocellular depressor area (GiDA) is a functionally defined subdivision of the medullary gigantocellular reticular formation where vasodepressor responses are evoked by glutamate nanoinjections. The GiDA also contains reticulospinal neurons that contain the α2A-adrenergic receptor (α2A-AR). In the present study, we sought to determine whether nanoinjections of the α2-AR agonist clonidine into the GiDA evoke cardiovascular responses and whether these responses can be attributed to the α2-AR. We found that nanoinjections of clonidine into the GiDA evoke dose-dependent decreases in arterial pressure and heart rate. These responses were equivalent in magnitude to responses produced by clonidine nanoinjections into the sympathoexcitatory region of the rostral ventrolateral medulla. Furthermore, the vasodepressor and bradycardic responses produced by clonidine injections into the GiDA were blocked in a dose-dependent fashion by the highly selective α2-AR antagonist 2-methoxyidazoxan, but not by prazosin, which is an antagonist at both the α1-AR and the 2B subtype of the α-AR. The antagonism by 2-methoxyidazoxan was site specific because injections of the antagonist into the rostral ventrolateral medulla failed to block the responses evoked by clonidine injections into the GiDA. These findings support the notion that clonidine produces sympathoinhibition through multiple sites within the medullary reticular formation, which is consistent with the wide distribution of the α2A-AR in reticulospinal neurons. These data also suggest that clonidine may have multiple mechanisms of action because it evokes a cardiovascular depressive response from regions containing neurons that have been determined to be both sympathoinhibitory and sympathoexcitatory. The American Society for Pharmacology and Experimental Therapeutics ER -