Serotonin 1A facilitation of frog motoneuron responses to afferent stimuli and to N-methyl- d-aspartate

The effects of serotonin and excitatory amino acids on motoneurons were examined by sucrose gap recordings from the ventral root of the isolated, hemisected frog spinal cord superfused with magnesium-free, carbonate-buffered Ringer solution. Low concentrations of serotonin (0.1 μM) and the serotonin 1A agonist8-hydroxy-2-( n-dipropylamino)tetralin (8-OH-DPAT; 0.01 μM) significantly increased the duration and amplitude of the polysynaptic components of ventral root potentials produced by dorsal root stimulation. The facilitations of the ventral root potentials were blocked by the serotonin 1A antagonist spiroxatrine, but were unaffected by the serotonin 2 antagonist ketanserin or the serotonin 3 antagonist 1αH,3α,5αH-tropan-3-yl-3,-dichlorobenzoate (MDL 72222). The actions of 0.1 μM serotonin on motoneuron depolarizations evoked by the putative excitatory amino acid transmitters l-glutamate and l-aspartate were quite variable, but in the presence of ketanserin (20 μM), small consistent increases in amino acid-induced motoneuron depolarizations were observed. 8-OH-DPAT significantly enhanced motoneuron depolarizations elicited by the selective excitatory amino acid agonist N-methyl- d-aspartate in both normal and tetrodotoxin-containing Ringer solution. Quisqualate-induced motoneuron depolarizations were also facilitated by 8-OH-DPAT in normal Ringer solution, but these increases were eliminated by addition of either tetrodotoxin or the N-methyl- d-aspartate antagonist d(−)-2-amino-5-phosphonovalerate to the Ringer superfusate. Kainate-depolarizations were not altered by low concentrations of serotonin or 8-OH-DPAT. Prior exposure of the cord to spiperone, but not ketanserin or MDL 72222 blocked the enhancement of N-methyl- d-aspartate-induced motoneuron depolarizations by 8-OH-DPAT. In the presence of saturating concentrations of glycine, 8-OH-DPAT facilitated N-methyl- d-aspartate responses. Increases in extracellular potassium activity, measured with ion-selective microelectrodes inserted in the intermediate gray matter, evoked by repetitive stimulation of myelinated afferent fibers in the sciatic nerve and by application of N-methyl- d-aspartate were significantly enhanced by 8-OH-DPAT. These findings are compatible with the notion that serotonergic activation of serotonin 1A receptors plays a role in regulating the responsiveness of frog spinal motoneurons to excitatory afferent inputs and to N-methyl- d-aspartate-mediated synaptic transmission.