Alpha2- and beta-adrenoceptors differentially modulate GABAA- and GABAB-mediated inhibition of red nucleus neuronal firing

In mesencephalic red nucleus (RN), GABA-induced inhibition of neuronal firing is modulated by noradrenaline acting on alpha(2)- and beta-adrenoceptors. Since both GABA(A) and GABA(B) receptors are present in the rat RN, we have recorded the firing activity of RN neurons in vivo from anaesthetized rats to study how GABA(A)- and GABA(B)-mediated effects are modulated by either alpha(2)- or beta-adrenoceptor activation. Both the GABA(A) agonist isoguvacine and the GABA(B) agonist baclofen depressed the firing of RN neurons. During simultaneous application of clonidine, an alpha(2)-adrenoceptor agonist, half of the isoguvacine- and baclofen-mediated responses were modified: isoguvacine-mediated inhibition was enhanced by 97% without any change in effect duration, whereas baclofen responses were either increased or slightly reduced in the same number of cases. Application of isoprenaline, a beta-adrenoceptor agonist, increased isoguvacine effect in 66% of neurons without modifying effect duration; the amount of increase (43%) was significantly lower than that induced by clonidine. On the other hand, in the presence of isoprenaline, baclofen response was reduced in 72% of neurons with respect to both the amount (52%) and the duration (34%) of effect. Taken together, these results indicate that alpha(2)-adrenoceptors mainly enhance GABA(A)-induced inhibition and induce mixed effects on GABA(B) response; on the other side, beta-adrenoceptors exert an opposite modulation on GABA effects, respectively, enhancing and depressing GABA(A)- and GABA(B)-mediated responses. (C) 2003 Elsevier Inc. All rights reserved.