Inhibition of reflex responses of neonate rat lumbar spinal cord by 5‐hydroxytryptamine

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Abstract
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 μm and for PSR depression was 9.0 ± 4.8 μm. 3 Blockade of neuronal uptake of 5-HT by citalopram (0.1 μm) 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 μm) 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 μm, for TFMPP was 0.93 ± 0.3 μm 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 μm) nor spiperone (1 μm) 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 μm, fluvoxamine 1 μm) usually reduced the MSR and, to a lesser extent, the PSR. Reflex depressions were reversed by ketanserin (1 μm). 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.