ABSTRACT
The excitatory responses evoked by glutamate and its agonists in secondary vestibular neurons of the rat were studied during microiontophoretic application of 5-hydroxytryptamine (5-HT). Ejection of 5-HT modified neuronal responsiveness to glutamate in 86% of the studied units, the effect being a depression of the excitatory responses in two-thirds of cases and an enhancement in the remaining third. 5-HT was also effective in modifying 94% of the responses evoked by N-methyl-d-aspartate (NMDA), inducing a depressive effect in 76% of cases and an enhancement in the remaining ones. Quisqualate-evoked effects were depressed and enhanced by 5-HT in about the same number of cases; in contrast, kainate-evoked responses were enhanced. The depressive action of 5-HT was mimicked by application of alpha-methyl-5-hydroxytryptamine (alpha-Me-5-HT), a 5-HT(2) receptor agonist, whereas the enhancing effect could be evoked by application of 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT(1A) receptor agonist. The 5-HT(2) receptor antagonist ketanserin was able to reduce, but not to block totally, the depressive action of 5-HT on glutamate- or NMDA-evoked responses. No significant difference was detected between neuronal responses in the lateral and the superior vestibular nucleus. These results indicate that 5-HT is able to modulate the responsiveness of secondary vestibular neurons to excitatory amino acids. Its action is mostly depressive, involves 5-HT(2) receptors, and is exerted on NMDA receptors. A minor involvement of other 5-HT receptors (at least 5-HT(1A)) and other glutamate receptors (for quisqualate and kainate) in the modulatory action of 5-HT is plausible.
Subject(s)
Glutamic Acid/pharmacology , Neurons/drug effects , Neurons/physiology , Serotonin/pharmacology , Vestibular Nuclei/drug effects , Vestibular Nuclei/physiology , Animals , Evoked Potentials/drug effects , Evoked Potentials/physiology , Excitatory Amino Acid Agonists/pharmacology , Kainic Acid/pharmacology , N-Methylaspartate/pharmacology , Quisqualic Acid/pharmacology , Rats , Rats, Wistar , Receptors, Amino Acid/physiology , Receptors, N-Methyl-D-Aspartate/physiology , Serotonin Receptor Agonists/pharmacology , Vestibular Nuclei/cytologyABSTRACT
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 rostral RN and a depression in those in the caudal RN. The application of 8-hydroxy-2(di-n-propylamino)tetralin, a specific 5-HT(1A) receptor agonist, enhanced GABA responses, whereas alpha-methyl-5-hydroxytryptamine, a 5-HT(2A) receptor agonist, depressed them. Both the 5-HT(2) antagonist methysergide and the 5-HT(2A) 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(A) 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-HT(1A) and 5-HT(2A) receptors. The functional significance of a serotonergic control on GABAergic inhibitory effects in RN is discussed.
