This animal study (n=69) examined whether DMT (1mg/kg/h) administration achieves neuroprotection via Sig-1R activation during an experimentally induced forebrain ischemia in rats and found that DMT attenuated the electrophysiological signature neurodegeneration even when 5-HTR binding was inhibited with a serotonergic antagonist, which confirmed the neuroprotective role of Sig-1R activation in their hypothesis.
Abstract
“Introduction: Dimethyltryptamine (DMT), an endogenous ligand of sigma-1 receptors (Sig-1Rs), acts against systemic hypoxia, but whether DMT may prevent cerebral ischemic injury is unexplored.
Methods: Here global forebrain ischemia was created in anesthetized rats and aggravated with the induction of spreading depolarizations (SDs) and subsequent short hypoxia before reperfusion. Drugs (DMT, the selective Sig-1R agonist PRE-084, the Sig-1R antagonist NE-100, or the serotonin receptor antagonist asenapine) were administered intravenously alone or in combination while physiological variables and local field potential from the cerebral cortex was recorded. Neuroprotection and the cellular localization of Sig-1R were evaluated with immunocytochemistry. Plasma and brain DMT content was measured by 2D-LC-HRMS/MS. The affinity of drugs for cerebral Sig-1R was evaluated with a radioligand binding assay.
Results: Both DMT and PRE-084 mitigated SDs, counteracted with NE-100. Further, DMT attenuated SD when co-administered with asenapine, compared to asenapine alone. DMT reduced the number of apoptotic and ferroptotic cells and supported astrocyte survival. The binding affinity of DMT to Sig-1R matched previously reported values. Sig-1Rs were associated with the perinuclear cytoplasm of neurons, astrocytes and microglia, and with glial processes.
Discussion: According to these data, DMT may be considered as adjuvant pharmacological therapy in the management of acute cerebral ischemia.”
Authors: Írisz Szabó, Viktória É. Varga, Szabolcs Dvorácskó, Attila E. Farkas, Tímea Kömöczi, Róbert Berkecz, Szilvia Kecskés, Àkos Menyhárt, Rita Frank, Dóra Hantosi, Nicholas V. Cozzi, Ede Frecska, Csaba Tömmböly, István A. Krizbai, Ferenc Bari & Eszter Farkas
Summary of N,N-Dimethyltryptamine attenuates spreading depolarization and restrains neurodegeneration by sigma-1 receptor activation in the ischemic rat brain
Introduction
DMT is a natural indole alkaloid found in plants and is known for its psychedelic effects. It is also found in mammalian tissues and body fluids, but is rapidly biodegraded by monoamine oxidases, which may be the reason for the very low endogenous DMT concentration measured.
The physiological and pathophysiological role of endogenous DMT has been the subject of ongoing debate and speculations. It has been claimed to have psychedelic and behavioral effects, a potential role in psychiatric disorders and altered states of consciousness, as well as a potential tissue protective and specific neuroprotective potential.
Find this paper
https://doi.org/10.1016/j.neuropharm.2021.108612
Open Access | Google Scholar | Backup | 🕊
Study details
Compounds studied
DMT
Topics studied
Neuroscience
Traumatic Brain Injury
Study characteristics
Animal Study
Participants
69