INHIBITION OF REFLEX RESPONSES OF NEONATE RAT LUMBAR SPINAL-CORD BY 5-HYDROXYTRYPTAMINE

1 Monosynaptic (MSR) and polysynaptic (PSR) segmental reflex responses were recorded from a ventral root of the neonate rat hemisected spinal cord. Amplitudes of the two components were monitored with a peak height detector. 2 5-Hydroxytryptamine (5-HT) depressed the MSR and PSR in a concentration-dependent manner. The IC50 for MSR depression was 9.5 +/- 3.2-mu-M and for PSR depression was 9.0 +/- 4.8-mu-M. 3 Blockade of neuronal uptake of 5-HT by citalopram (0.1-mu-M) greatly increased sensitivity to 5-HT. In the presence of citalopram, the IC50 for MSR depression was 30 +/- 18 nM and for PSR depression was 89 +/- 23 nM. 4 5-HT did not depress the MSR or the PSR by releasing glycine since strychnine (1-mu-M) did not prevent these actions of 5-HT. 5 5-Carboxamidotryptamine (5-CT), 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), RU 24969, 1-[3-(trifluoromethyl)phenyl]-piperazine (TFMPP) and methysergide were full agonists for depression of the MSR. The IC50 for 5-CT was 3.6 +/- 0.5 nM, for 8-OH-DPAT was 0.4 +/- 0.04-mu-M, for TFMPP was 0.93 +/- 0.3-mu-M and for methysergide was 21.8 +/- 3.0 nM. The order of potency was 5-CT > methysergide > 5-HT > 8-OH-DPAT > TFMPP. 6 8-OH-DPAT, RU 24969, TFMPP and methysergide had either no or only a minor action in reducing the PSR. 5-CT caused a 50% depression at the highest concentration tested (30 nM). 7 Neither ketanserin (1-mu-M) nor spiperone (1-mu-M) caused appreciable blockade of 5-HT depression of the MSR or 5-HT depression of the PSR. 8 Blockers of neuronal 5-HT uptake (citalopram 0.1 or 1-mu-M, fluvoxamine 1-mu-M) usually reduced the MSR and, to a lesser extent, the PSR. Reflex depressions were reversed by ketanserin (1-mu-M). 9 It was concluded that 5-HT has a potent depressant action on segmental reflexes; depression of the MSR is unrelated to depolarization of motoneurones. Although depression of the MSR was mimicked by 5-HT1A receptor ligands, the action of endogenous 5-HT may be mediated through 5-HT2 receptors. Exogenous 5-HT may act at a mixture of 5-HT receptor subtypes to depress the MSR.