Serotonin modifies the neuronal inhibitory responses to gamma-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 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.
Licata
F
F
Department of Physiological Sciences, University of Catania, Catania, 95125, Italy.
Li Volsi
G
G
Di Mauro
M
M
Fretto
G
G
Ciranna
L
L
Santangelo
F
F
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001931:Brain Mapping; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D007478:Iontophoresis; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1; D012012:Red Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D005680:gamma-Aminobutyric Acid