Opposite effects of N,N-dimethyltryptamine (DMT) and 5-methoxy-n,n-dimethyltryptamine (5-MeODMT) on acoustic startle: spinal vs brain sites of action.
Randall L. Commissaris, M Davis
Neuroscience & Biobehavioral Reviews 1982 DOI: 10.1016/0149-7634(82)90034-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rat |
| Interventions | DMT 5-MeODMT 5-hydroxytryptamine |
| Topics | 5-MeO-DMT DMT |
| Citations | 25 |
| Key findings | DMT and 5-MeODMT are equally potent in depressing startle via brain actions, but only 5-MeODMT increases startle through spinal excitatory effects. |
Abstract
The present studies examined the role of the spinal cord and the brain in mediating the effects of the hallucinogens N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) on the acoustic startle response in the rat. Systemic administration of these agents, which distributes to both the brain and spinal cord, produced opposite effects, as DMT depressed and 5-MeODMT increased acoustic startle. However, when administered directly into the lateral ventricle in the forebrain (intraventricular administration) 5-hydroxytryptamine (5-HT), DMT and 5-MeODMT all depressed acoustic startle, DMT and 5-MeODMT being about equipotent in this regard. In contrast, when administered directly into the spinal cord subarachnoid space (intrathecal administration), 5-HT and 5-MeODMT increased startle, whereas DMT was without effect. In another series of studies, the effects of systemically-administered DMT and 5-MeODMT on the "startle" elicited by electrical stimulation of the nucleus reticularis pontis caudalis (RPC) were determined. Since the RPC is the last nucleus of the primary startle circuit before the spinal cord, agents which act downstream from the RPC (i.e., in the lower brainstem and spinal cord) would be expected to alter RPC-elicited "startle," while agents which act upstream from the RPC would be without effect. Given systemically, 5-MeODMT markedly increased RPC-elicited "startle" while DMT was without effect. These data indicate that DMT and 5-MeODMT are equipotent in depressing startle through actions in the brain. In contrast, the difference in the effects of DMT and 5-MeODMT on acoustic startle is related to the spinal excitatory effects of 5-MeODMT which DMT does not possess. From the present results it is suggested that the relative potencies of DMT and 5-MeODMT in other behavioral measures may relate to the role of brain (equipotent) or spinal (5-MeODMT more potent than DMT) sites of action for the various behaviors.
Comparable studies
Other experimental studies on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT. Human cerebral organoids | 2017 | Experimental study | |
| Bufo alvarius: a potent hallucinogen of animal origin. Bufo alvarius toad venom | 1994 | Experimental study | |
| Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment Volunteers | 2019 | Within-subjects experimental study | n = 11 |
| Unmasking of a neonatal somatovesical reflex in adult cats by the serotonin autoreceptor agonist 5-methoxy-N,N-dimethyltryptamine. Adult cats | 1990 | Experimental study | n = 10 |
| Studies on the Mechanism of Action of Monoamine Oxidase: Metabolism of N,N-Dimethyltryptamine and N,N-Dimethyltryptamine-N-Oxide | 1962 | Experimental study |
Citations in the library
Cited by 3
- A Single Dose of 5-MeO-DMT Stimulates Cell Proliferation, Neuronal Survivability, Morphological and Functional Changes in Adult Mice Ventral Dentate Gyrus Frontiers in Molecular Neuroscience September 4, 2018
- Neurochemical and Neurophysiological Effects of Intravenous Administration of N,N -Dimethyltryptamine in Rats Journal of Neuroscience December 19, 2025
- Psychedelics and Autism Therapy: A Review of Current Research and Future Directions Current Issues in Molecular Biology April 18, 2026
Cites 5
- The effects of lysergic acid diethylamide and mescaline-derived hallucinogens on sensory-integrative function: tactile startle. Journal of Pharmacology and Experimental Therapeutics December 1, 1978
- Hallucinogenic agents as discriminative stimuli: a correlation with serotonin receptor affinities. Psychopharmacology 1980
- 5-Methoxy-N,N-dimethyltryptamine: spinal cord and brainstem mediation of excitatory effects on acoustic startle. Psychopharmacology 1980
- Effects of N,N-Dimethyltryptamine (DMT) and 5-Methoxy-N,N-dimethyltryptamine (5-MeODMT) on shock elicited fighting in rats Pharmacology, Biochemistry, and Behavior July 1, 1978
- Neurotransmitter basis of the behavioral effects of hallucinogens. Neuroscience & Biobehavioral Reviews 1982