Activation of 5-HT1C/2 receptors depresses polysynaptic reflexes and excitatory amino acid-induced motoneuron responses in frog spinal cord.
Sucrose gap recordings from the ventral roots of isolated, hemisected frog spinal cords were used to evaluate the effects of high concentrations of serotonin (5-HT) and alpha-methyl-5-HT (alpha-Me-5-HT) on the changes in motoneuron potential produced by dorsal root stimulation and by excitatory amino acids and agonists. Bath application of 5-HT in concentrations of 10 microM or greater produced a concentration-dependent motoneuron depolarization. Polysynaptic ventral root potentials evoked by dorsal root stimuli were reduced in both amplitude and area by 5-HT or alpha-Me-5-HT (both 100 microM). This may result from a reduction of the postsynaptic sensitivity of motoneurons to excitatory amino acid transmitters because 5-HT significantly depressed motoneuron depolarizations produced by addition of L-glutamate and L-aspartate to the superfusate. Similarly, 5-HT reduced depolarizations produced by the excitatory amino acid agonists N-methyl-D-aspartate (NMDA), quisqualate, alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA), and kainate. alpha-Me-5-HT reduced NMDA depolarizations. Tetrodotoxin (TTX) did not affect the ability of 5-HT to attenuate NMDA or kainate depolarizations, but did eliminate the 5-HT-induced attenuation of quisqualate and AMPA depolarizations. The glycine receptor site associated with the NMDA receptor did not appear to be affected by 5-HT because saturation of the site by excess glycine did not alter the 5-HT-induced depression of NMDA responses. The 5-HT1C/2 antagonist ketanserin and the 5-HT1A/2 antagonist spiperone significantly attenuated the 5-HT-induced depression of NMDA-depolarizations.(ABSTRACT TRUNCATED AT 250 WORDS)
Holohean
A M
AM
Neurophysiology Laboratory, Veterans Affairs Medical Center, Miami, FL.
Hackman
J C
JC
Shope
S B
SB
Davidoff
R A
RA
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects*; D011894:Rana pipiens; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012018:Reflex / Q000187:drug effects*; D012584:Sciatic Nerve / Q000166:cytology / Q000187:drug effects; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects; D013126:Spinal Nerve Roots / Q000502:physiology
D000596:Amino Acids; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; C042390:alpha-methylserotonin; D012701:Serotonin