Vol. 289, Issue 2, 688-694, May 1999

Clonidine Evokes Vasodepressor Responses via ₂-Adrenergic Receptors in Gigantocellular Reticular Formation¹

Sue A. Aicher and Carrie T. Drake

Department of Neurology and Neuroscience, Division of Neurobiology, Cornell University Medical College, New York, New York

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 _2A-adrenergic receptor (_2A-AR). In the present study, we sought to determine whether nanoinjections of the ₂-AR agonist clonidine into the GiDA evoke cardiovascular responses and whether these responses can be attributed to the ₂-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 ₂-AR antagonist 2-methoxyidazoxan, but not by prazosin, which is an antagonist at both the ₁-AR and the 2B subtype of the -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 _2A-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.