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 Mg²⁺ in the medium. Stimulation of a dorsal root evoked monosynaptic reflex potential (MSP) and polysynaptic reflex potential (PSP) in the segmental ventral root in Mg²⁺-free medium where the voltage-dependent blockade of NMDAreceptors is absent. The 5-HT (0.3–50 μM) in the Mg²⁺-free medium depressed the MSPand PSP in a concentration-dependent manner. At 30 μM of 5-HT, the depression was 57% and 95% for MSP and PSP, respectively, and no further depression was seen at 50 μM. The 5-HT-induced depression of the reflexes in the Mg²⁺-free medium was blocked by ondansetron (5-HT₃ receptor antagonist), but not by spiperone (5-HT_2A/2C antagonist). In the Mg²⁺-free medium, phenylbiguanide (5-HT₃ agonist) also depressed the MSPand PSP in a concentration-dependent manner and was blocked by ondansetron. Addition of Mg²⁺ (1.3 mM) to the medium abolished the PSP and decreased the MSPby 30%. In the presence of Mg²⁺, 5-HT (1–50 μM) also depressed the MSP in a concentration-dependent manner. At 10 μM of 5-HT, there was approximately 20% depression and at 50 μM the depression was 100%. The 5-HT-induced depression of MSP in the Mg²⁺-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 MSPinvolves 5-HT₃ receptors in the Mg²⁺-free medium and 5-HT_2A/2C in the presence of Mg²⁺ when NMDA receptors are in the closed state.