Abstract
N,N-dimethyltryptamine (DMT), a psychedelic compound identified endogenously in mammals, is biosynthesized by aromatic-L-amino acid decarboxylase (AADC) and indolethylamine-N-methyltransferase (INMT). Whether DMT is biosynthesized in the mammalian brain is unknown. We investigated brain expression of INMT transcript in rats and humans, co-expression of INMT and AADC mRNA in rat brain and periphery, and brain concentrations of DMT in rats. INMT transcripts were identified in the cerebral cortex, pineal gland, and choroid plexus of both rats and humans via in situ hybridization. Notably, INMT mRNA was colocalized with AADC transcript in rat brain tissues, in contrast to rat peripheral tissues where there existed little overlapping expression of INMT with AADC transcripts. Additionally, extracellular concentrations of DMT in the cerebral cortex of normal behaving rats, with or without the pineal gland, were similar to those of canonical monoamine neurotransmitters including serotonin. A significant increase of DMT levels in the rat visual cortex was observed following induction of experimental cardiac arrest, a finding independent of an intact pineal gland. These results show for the first time that the rat brain is capable of synthesizing and releasing DMT at concentrations comparable to known monoamine neurotransmitters and raise the possibility that this phenomenon may occur similarly in human brains.
Highlights
Potential for correspondingly high levels of DMT, cellular colocalization of INMT and amino acid decarboxylase (AADC) transcripts has not yet been reported in any tissue
We report [1] cortical expression of INMT mRNA in rat and human brain, [2] colocalization of INMT and AADC mRNA in the same cells in rat brain, and [3] predominately non-overlapping expression of INMT with AADC mRNA in rat peripheral organs including the adrenal, kidney, lung, and heart
We further show that DMT is present in rat visual cortex in pineal-intact and pinealectomized animals
Summary
Potential for correspondingly high levels of DMT, cellular colocalization of INMT and AADC transcripts has not yet been reported in any tissue. Studies to date assessing levels of DMT in human peripheral bodily fluids have only reported it in trace amounts[11], calling into question any physiological role. In order to address some of these issues, this study examined expression of INMT mRNA in rat and human brain tissues using in situ hybridization. We conducted double in situ hybridization studies to probe the co-expression of INMT and AADC mRNA in rat brain and periphery. To investigate whether DMT brain levels are inducible by physiological alterations, we assessed its levels in rat brain following cardiac arrest with or without the pineal gland, as a prior study from our lab demonstrated a surge in the levels of select neurotransmitters in rat visual cortex following cardiac arrest using this technique[21]
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