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.
Two types of hallucinogens that affect serotonin systems have both shared and distinct effects on spinal reflexes in rats. 5-MeODMT (an indolealkylamine) decreased the monosynaptic reflex in a dose-dependent way, while DOI (a phenylalkylamine) increased it. Both drugs increased the polysynaptic reflex. Antagonists blocking 5-HT2 receptors prevented DOI's effects on the monosynaptic reflex but only partially blocked those of 5-MeODMT. The same antagonists inhibited DOI-induced changes in the polysynaptic reflex but not those caused by 5-MeODMT. Neither propranolol nor MDL 72222 blocked either drug's effects. Both hallucinogens increased motoneuron excitability via 5-HT2 receptors, but only 5-MeODMT inhibited the monosynaptic reflex pathway.