The drug 5-MeODMT, which acts on serotonin receptors, increased the acoustic startle reflex in rats starting at a dose of 0.12 mg/kg, with the effect growing stronger up to the highest dose tested (8.0 mg/kg). This enhancement occurred even in rats whose brains had been disconnected from the spinal cord or when the drug was applied directly to the spinal cord, indicating the effect originates in the spinal cord. Several serotonin-blocking drugs (cinanserin, cyproheptadine, propranolol) completely blocked this excitatory effect, while others did not. The findings support a theory that serotonin receptors in the spinal cord amplify startle, while those in the forebrain dampen it.
The hallucinogens DMT and 5-MeODMT have opposite effects on the acoustic startle response in rats when given systemically: DMT depresses it while 5-MeODMT increases it. When injected directly into the brain, both drugs depress startle equally. When injected into the spinal cord, 5-MeODMT increases startle but DMT has no effect. Tests using electrical stimulation of a brainstem nucleus confirm that 5-MeODMT acts in the spinal cord to enhance startle, whereas DMT does not. The authors suggest that the differing behavioral effects of these drugs may depend on whether their action is primarily in the brain (where both are equally potent) or the spinal cord (where only 5-MeODMT is active).