Contribution of AMPA/kainate receptors in the rostral ventrolateral medulla to the hypotensive and sympathoinhibitory effects of clonidine.

Wang WZ, Wang LG, Gao L, Wang W. Am J Physiol Regul Integr Comp Physiol. 2007 Sep;293(3):R1232-8 In this paper, they wanted to look at the how clonidine injections (IV or in to the RVLM) have a sympatholytic effect, so they took the simple and obvious course of action - use a glutamate receptor inhibitor in the RVLM to block the inhibitory effect of clonidine. Yes, that was a fun bit of sarcasm because this paper was not easy to understand. They were able to use microinjections of CNQX, an AMPA type glutamate receptor antagonist to block the inhibitory effect of clonidine, which is apparently known to induce GABA release in the RVLM. It seems that the effect of clonidine here is not actually on presympathetic neurons, but possibly on presynaptic GABAergic terminals, which is something that is possible. It's strange, because clonidine is not known to be an AMPA agonist, so I guess that blockade of AMPA receptors on presynaptic gabaergic fibers removes just enough excitation to counteract the effect of clonidine through the receptors it does act on. And of course, it is safe to assume that CNQX microinjections in to the RVLM also blocked the AMPA receptors on presympathetic neurons, but we already know that this can have little to no effect on sympathetic tone (which is what they also were able to show in this study). So it's a little hard to figure out what's going on, but the results speak for themselves. -DH