5-HT2/5-HT1C receptor-mediated facilitatory action on unit activity of ventral horn cells in rat spinal cord slices.

Certain drugs that activate serotonin receptors, specifically 5-HT2 and 5-HT1C types, increase the excitability of motor neurons in the spinal cord of adult rats. The compounds 5-MeODMT and DOI were the most potent at boosting the firing probability of these cells. Blocking 5-HT2 or 5-HT1C receptors with specific antagonists suppressed this effect, while blocking other serotonin receptor types did not. This indicates that 5-HT2 and 5-HT1C receptors mediate the facilitatory influence of serotonin-like drugs on spinal motor neuron activity.

Study at a glance

Abstract

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.