<EM>N,N</EM>-DIMETHYLTRYPTAMINE (DMT) IS NEITHER FORMED NOR RETAINED IN SEROTONIN TERMINALS IN THE RAT BRAIN

If the mammalian brain contains an endogenous pool of the psychedelic substance N,N-dimethyltryptamine (DMT), which may act as a co-transmitter with serotonin (5-HT), is still debated. Here we present data, testing the hypotheses that endogenous DMT would accumulate in rat brain after inhibiting its major degrading enzyme (monoamine oxidase) with pargyline, however endogenous DMT levels were below the detection limit of our analytic method, despite pargyline pretreatment. Relying on exogenous treatment of DMT, we then tested the hypothesis that pretreatment with inhibitors of plasma membrane 5-HT uptake (escitalopram) or the vesicular monamine transporter 2 (dihydrotetrabenazine) would reduce the retention in brain of exogenous DMT after administration of DMT+harmine (1 mg/kg each). Here, escitalopram did not alter the disposition of exogenous DMT or its metabolite 3-IAA, whereas dihydrotetrabenazine slightly increased 3-IAA formation in some brain regions. In conclusion, we could not detect an endogenous DMT pool in rat brain and saw scant evidence of any retention of exogenous DMT in 5-HT terminals, showing that DMT most likely do not act as an endogenous neurotransmitter through serotonergic neuron co-release.