Injecting 5-methoxy-N,N-dimethyltryptamine into the brain's ventricles altered pain sensitivity in rats, measured by the tail-flick test. Low doses (1.6 to 25 micrograms) reduced tail-flick latencies by 13-24%, indicating hyperalgesia (increased pain sensitivity), likely from decreased activity in descending serotonergic neurons. Moderate doses (50 and 100 micrograms) produced a biphasic response: initial hyperalgesia followed by analgesia. The highest dose (400 micrograms) increased latencies by 28-39%, indicating analgesia, probably by stimulating spinal postsynaptic serotonergic receptors.
5-MeO-DMT, a psychedelic compound, inhibits the reuptake of serotonin in rat brain tissue at concentrations between 0.5 and 500 micromolar, affecting the striatum, hippocampus, and hypothalamus. At higher concentrations (10 micromolar), it also inhibits dopamine reuptake and triggers the release of both serotonin and dopamine from nerve endings. These findings suggest that 5-MeO-DMT's effects as a serotonin agonist may involve blocking reuptake, not just directly stimulating receptors as previously thought.