Serotonin modifies the neuronal inhibitory responses to gamma-aminobutyricacid in the red nucleus: A microiontophoretic study in the rat

The effects of 5-hydroxytryptamine (5-HT) on the inhibitory responses evoke d by gamma -aminobutyric acid (GABA) in neurons of the red nucleus (RN) wer e studied using a microiontophoretic technique. Extracellular unitary recor dings performed in anesthetized rats demonstrated that 5-HT ejection influe nced 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-depen dent, although enhancements or depressions of the GABA responses were respe ctively inversely and directly related to the doses of 5-HT applied. The ty pe of modulation exerted by 5-HT on the GABA responses was independent of t he action of the amine on background firing. In fact, 5-HT induced an enhan cement of the GABA responses in neurons mostly located in the rostraI RN an d 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 ago nist, 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 an tagonists mimicked the enhancing action of 5-HT on the GABA responses or we re ineffective. Application of bicuculline, a GABA, receptor antagonist, en hanced 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 modulat e GABA-evoked responses in RN neurons by acting on both 5-HT1A and 5-HT2A r eceptors. The functional significance of a serotonergic control on GABAergi c inhibitory effects in RN is discussed. (C) 2001 Academic Press.