DESCENDING INHIBITION IN THE NEONATE RAT SPINAL-CORD IS MEDIATED BY 5-HYDROXYTRYPTAMINE

The inhibitory effects of a stimulus to the thoracic cord on lumbar segmental A single stimulus to the latero-ventral cord surface at T11-T12 evoked fast and slow responses in both L4 ventral roots and inhibited rapid segmental reflexes, both ipsi- and contralaterally. The monosynaptic reflex (MSR) was strongly inhibited and the polysnaptic reflex (PSR) and contralateral fast reflex (CON FAST) were inhibited by 30-40%. The inhibition rose to a maximum 2 sec after the conditioning stimulus, plateaued between 2-20 sec and gradually waned to low levels by 100 sec. The slow segmental responses were not inhibited. Inhibition of the MSR was only elicited ipsilaterally and that of PSR was reduced by about 50% on stimulation of the contralateral thoracic cord; inhibition of CON FAST could be evoked from either side of the cord. Inhibition of the MSR from 2-50 sec was greatly reduced by 5-HT2 receptor antagonists. Ketanserin (1 muM) and ritanserin (1 muM) were equally effective but LY 53857 (1 muM) had a weaker blocking action. Only ketanserin reduced inhibition of the PSR. Prazosin (0.1 muM) did not affect inhibition of the MSR but yohimbine (1 muM) blocked it as effectively as ketanserin. This was probably due to 5-HT2 receptor blockade, since 0.1 muM yohimbine had little blocking action and 1 muM idazoxan none, nor did 0.1 muM clonidine mimic inhibition of the MSR. Inhibition of the MSR and PSR was not reduced by 1 muM naloxone, 1 muM strychnine, 1 muM bicuculline nor 10-30 muM APV. Consistent with the release of 5-HT by descending pathways, the 5-HT uptake blocker, citalopram 0.1 muM and the 5-HT releaser, p-chloroamphetamine 1 muM, depressed segmental reflexes, especially the MSR. 5-Hydroxytryptamine did not have the same depressant action on segmental reflexes as stimulation of the thoracic cord; the slow responses were most affected. Both 8-OH-DPAT (1-3 muM) and dipropyl-5-CT (1 muM) preferentially depressed the MSR. Neither spiroxatrine (0.1 muM) nor methysergide (5-10 nM) altered inhibition of the MSR. The concentration of ketanserin required to reduce sub-maximal inhibition by 50% was estimated using 2 concentrations of antagonist. The pIC50, estimated for the blockade by ketanserin of inhibition 20-50 sec after a conditioning stimulus, was 7.3-7.5. It is concluded that inhibition of the MSR and PSR does not involve mediation by glycine, GABA(A) nor NMDA receptors, nor release of enkephalins nor noradrenaline. The late phase of inhibition of the MSR appears to be dependent on 5-HT, acting at 5-HT2 receptors.