Serotonin modifies the neuronal inhibitory responses to γ-aminobutyric acid in the red nucleus:: A microiontophoretic study in the rat

The effects of 5-hydroxytryptamine (5-HT) on the inhibitory responses evoked by gamma -aminobutyric acid (GABA) in neurons of the red nucleus (RN) were studied using a microiontophoretic technique. Extracellular unitary recordings performed in anesthetized rats demonstrated that 5-HT ejection influenced GABA-evoked inhibition in 94% of RN neurons, enhancing them in 52% and depressing them in 46% of cases. Both effects were specific and dose-dependent, although enhancements or depressions of the GABA responses were respectively inversely and directly related to the doses of 5-HT applied. The type of modulation exerted by 5-HT on the GABA responses was independent of the action of the amine on background firing. In fact, 5-HT induced an enhancement of the GABA responses in neurons mostly located in the rostraI RN and a depression in those in the caudal RN. The application of 8-hydroxy-2(di-n-propylamino)tetralin, a specific 5-HT2A receptor agonist, enhanced GABA responses, whereas alpha -methyI-5-hydroxytryptamine, a 5-HT,A receptor agonist, depressed them. Both the 5-HT2 antagonist methysergide and the 5-MT, selective antagonist ketanserin were able to block partially or totally the depressive action of 5-HT on GABA responses. In contrast, the same 5-HT antagonists mimicked the enhancing action of 5-HT on the GABA responses or were ineffective. Application of bicuculline, a GABA, receptor antagonist, enhanced the excitatory action of 5-HT on the background firing and slightly reduced the inhibitory action. It is concluded that 5-HT is able to modulate GABA-evoked responses in RN neurons by acting on both 5-HT1A and 5-HT2A receptors. The functional significance of a serotonergic control on GABAergic inhibitory effects in RN is discussed. (C) 2001 Academic Press.