Alpha 2- 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 alpha2- and beta-adrenoceptors. Since both GABAA and GABAB receptors are present in the rat RN, we have recorded the firing activity of RN neurons in vivo from anaesthetized rats to study how GABAA- and GABAB-mediated effects are modulated by either alpha2- or beta-adrenoceptor activation. Both the GABAA agonist isoguvacine and the GABAB agonist baclofen depressed the firing of RN neurons. During simultaneous application of clonidine, an alpha2-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 alpha2-adrenoceptors mainly enhance GABAA-induced inhibition and induce mixed effects on GABAB response; on the other side, beta-adrenoceptors exert an opposite modulation on GABA effects, respectively, enhancing and depressing GABAA- and GABAB-mediated responses.