5-Methoxy-N,N-dimethyltryptamine (5-MeODMT) and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) facilitate motoneuron excitability through 5-HT1C/5-HT2 receptors in rats. Using spinal cord slices prepared from adult rats, we recorded unitary cell discharges, evoked by local stimulation of the adjacent site, extracellularly in the motor nuclei of the ventral horn. 5-MeODMT, DOI, 5-hydroxytryptamine (5-HT), 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) and tandospirone facilitated the probability of firing in the motor nuclei, with 5-MeODMT and DOI being the most potent. The effect of 5-MeODMT was significantly suppressed by ketanserin (a 5-HT2 receptor-selective antagonist), spiperone (a 5-HT1A/5-HT2 receptor antagonist) and cyproheptadine (a 5-HT1C/5-HT2 receptor antagonist), but not by 3-tropanyl-3,5-dichlorobenzoate (MDL 72222, a 5-HT3 receptor-selective antagonist) or pindolol (a 5-HT1A/5-HT1B receptor antagonist). This suggests that 5-HT2 and/or 5-HT1C receptors are involved in the facilitatory effects of 5-HT receptor agonists on the synaptic activity of ventral horn cells.