THE PREVENTION BY INHIBITORS OF BRAIN PROTEIN SYNTHESIS OF THE HYPERACTIVITY AND HYPERPYREXIA PRODUCED IN RATS BY MONOAMINE OXIDASE INHIBITION AND THE ADMINISTRATION OF L‐TRYPTOPHAN OR 5‐METHOXY‐N,N‐DIMETHYLTRYPTAMINE
D. G. Grahame‐Smitha
Journal of Neurochemistry October 1, 1972 DOI: 10.1111/j.1471-4159.1972.tb01295.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rats and mice |
| Interventions | Tranylcypromine Cycloheximide Acetoxycycloheximide Emetine Dehydroemetine Puromycin |
| Topics | 5-MeO-DMT DMT |
| Key findings | Inhibitors of brain protein synthesis block hyperactivity produced by tranylcypromine plus L-tryptophan or 5-MeODMT, with inhibition appearing only when brain protein synthesis is reduced by more than 65 percent. The authors propose that the behavioral excitant effects of brain serotonin and 5-MeODMT are mediated by a brain protein with a short biological half-life. |
Abstract
Abstract— In rats treated with a monoamine oxidase inhibitor, (tranylcypromine), L‐ tryptophan produces a stereotyped syndrome of hyperactivity and hyperpyrexia due to an increased rate of brain serotonin (5‐hydroxytryptamine) synthesis. Pretreatment of rats with intraperitoneal injections of cycloheximide, acetoxycycloheximide, emetine and dehydroemetine and of mice with puromycin inhibited this syndrome. Cycloheximide also inhibited the hyperactivity caused by tranylcypromine and DL‐15‐hydroxtryptophan and did not affect the increased rate of brain serotonin ‘synthes’ is produced by tryptophan thus excluding a primary effect on tryptophan‐5‐hydroxylase. Inhibition of hyperactivity did not occur until brain protein synthesis was inhibited by greater than 65 per cent as measured by the incorporation of L‐[U‐14C]tyrosine into brain protein in vivo. Emetine, which has been shown to inhibit brain protein synthesis inhibited hyperactivity whereas isoemetine which did not inhibit brain protein synthesis, did not inhibit hyperactivity.Under conditions where cycloheximide inhibited hyperactivity produced by tranylcypromine and L‐tryptophan, a large dose of 5‐methoxy‐N,N‐dimethyltryptamine(5‐MeODMT) still produced hyperactivity showing that the rats were still capable of the same pattern of hyperactivity. However, cycloheximide did inhibit hyperactivity due to 5‐MeODMT, the degree of this inhibition being dependent upon a balance between the doses of cycloheximide and 5‐MeODMT. 5‐MeODMT probably acts directly within the brain to cause behavioural excitation and it seems likely that the inhibitors of brain protein synthesis interfere with the mechanism of action of brain 5HT and administered 5‐MeODMT rather than upon any aspect of synthesis, storage or release of brain 5HT. It is suggested that the behaviourally excitant effects of brain 5HT and 5‐MeODMT are mediated in some way by a brain protein with a short biological half‐life. Such a protein may act either as a factor specifically mediating the central effects of brain 5HT or as a factor regulating the neuronal response to excitation by 5HT and 5‐MeODMT.
Comparable studies
Other preclinical and animal studies on DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Mice and cell lines | 2009 | Experimental study | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Inhibitory effect of chlorpromazine on the syndrome of hyperactivity produced by l‐tryptophan or 5‐methoxy‐N,N‐dimethyltryptamine in rats treated with a monoamine oxidase inhibitor Rats | 1971 | Experimental study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study |