5-HT-induced depression of the spinal monosynaptic reflex potential utilizes different types of 5-HT receptors depending on Mg2+ availability.

Receptor subtypes involved in the 5-hydroxytryptamine (5-HT)-induced depression of synaptic transmission in neonatal rat spinal cords in vitro were evaluated in the absence or presence of Mg(2+) in the medium. Stimulation of a dorsal root evoked monosynaptic reflex potential (MSP) and polysynaptic reflex potential (PSP) in the segmental ventral root in Mg(2+)-free medium where the voltage-dependent blockade of NMDA receptors is absent. The 5-HT (0.3-50 microM) in the Mg(2+)-free medium depressed the MSP and PSP in a concentration-dependent manner. At 30 microM of 5-HT, the depression was 57% and 95% for MSP and PSP, respectively, and no further depression was seen at 50 microM. The 5-HT-induced depression of the reflexes in the Mg(2+)-free medium was blocked by ondansetron (5-HT(3) receptor antagonist), but not by spiperone (5-HT(2A/2C) antagonist). In the Mg(2+)-free medium, phenylbiguanide (5-HT(3) agonist) also depressed the MSP and PSP in a concentration-dependent manner and was blocked by ondansetron. Addition of Mg(2+) (1.3 mM) to the medium abolished the PSP and decreased the MSP by 30%. In the presence of Mg(2+), 5-HT (1-50 microM) also depressed the MSP in a concentration-dependent manner. At 10 microM of 5-HT, there was approximately 20% depression and at 50 microM the depression was 100%. The 5-HT-induced depression of MSP in the Mg(2+)-containing medium was antagonized by spiperone (p < 0.05, two-way ANOVA), but not by ondansetron. The results indicate that the 5-HT-induced depression of MSP involves 5-HT(3) receptors in the Mg(2+)-free medium and 5-HT(2A/2C) in the presence of Mg(2+) when NMDA receptors are in the closed state.