Serotonergic modulation of the responses to excitatory amino acids of rat dorsal horn neurons in vitro: implications for somatosensory transmission.
Serotonin (5-HT) is one of the major transmitters involved in supraspinal control of somatic sensation and nociception. The aim of the present study was to investigate if the 5-HT-induced modulation of sensory transmission in the dorsal horn could be due to regulation of neuronal responses to excitatory amino acids. Experiments were performed in an in vitro preparation of the young rat spinal cord. Responses to dorsal root stimulation (DR-EPSP) and to droplet application of N-methyl-D-aspartic acid (NMDA) and alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid (AMPA) were obtained by means of intracellular recordings of dorsal horn neurons. Bath applications of 5-HT (50 microM) generally caused reductions in amplitude and integrated area of DR-EPSPs and of responses to NMDA but the responses to AMPA were unaltered. A linear correlation was found between the effects of 5-HT on the DR-EPSP and on the NMDA response measured as percentage change in amplitude (r2 = 0.45; P < or = 0.01) and integrated area (r2 = 0.77; P < or = 0.001). The NMDA receptor antagonist d-AP5 (50 microM) completely abolished NMDA responses and caused a depression of the DR-EPSP similar to that of 5-HT. The 5-HT1 receptor agonist 5-carboxamidotryptamine (5-CT; 1 microM) mimicked the depressant effects of 5-HT but had a stronger depressant action on the DR-EPSP than 5-HT. The depression of NMDA responses induced by 5-HT and 5-CT was tetrodotoxin (1 microM) resistant. It is concluded that 5-HT-induced depression of NMDA responses explains partially the depressant action of 5-HT on dorsal horn synaptic transmission activating a postsynaptic site sensitive to 5-CT. The possible activation of coadjuvant mechanisms is discussed.
Lopez-Garcia
J A
JA
Departamento de Fisiología, Facultad de Medicina, Universidad de Alcalá, Madrid, Spain. FFJALG@ALCALA.ES
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D012677:Sensation / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C047087:5-carboxamidotryptamine