ACTIVATION OF 5-HT1C/2 RECEPTORS DEPRESSES POLYSYNAPTIC REFLEXES AND EXCITATORY AMINO ACID-INDUCED MOTONEURON RESPONSES IN FROG SPINAL-CORD

被引:13
作者
HOLOHEAN, AM
HACKMAN, JC
SHOPE, SB
DAVIDOFF, RA
机构
[1] UNIV MIAMI,SCH MED,DEPT NEUROL D45,POB 016960,MIAMI,FL 33101
[2] VET AFFAIRS MED CTR,NEUROPHYSIOL & SPINAL CORD PHARMACOL LABS,MIAMI,FL 33101
关键词
SEROTONIN; SPINAL CORD; FROG; MOTONEURON; EXCITATORY AMINO ACID;
D O I
10.1016/0006-8993(92)90736-S
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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-mu-M 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-mu-M). 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. The relatively selective 5-HT1A antagonist spiroxatrine and the selective 5-HT3 blocker MDL 72222 were without effect against the depressive effects of 5-HT. These observations support the notion that 5-HT putatively released from descending bulbospinal fibers can alter frog motoneuronal output. The data indicate that 5-HT1C/2 receptors affect the afferent input to motoneurons and do so by attenuation of NMDA receptor-mediated synaptic processes.
引用
收藏
页码:8 / 16
页数:9
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