Neurochemical investigations of the interaction of N,N-dimethyltryptamine with the dopaminergic system in rat brain

Abstract

Abstract. N,N-dimethyltryptamine (DMT) is a psychotomimetic indolealkylamine that has been suspected of being an endogenous causal factor in the aetiotogy of schizophrenia. Some aspects of its interaction with the dopaminergic system of the rat brain have been studied neurochemically, and comparisons have been made with the effects of d-amphetamine and apomorphine. In contrast to these two compounds, DMT has proved to be a potent, but short-acting MAO inhibitor with a rather selective effect on MAO A (serotonin-deaminating MAO).Like classical MAO inhibitors, DMT also greatly increases the accumulation of 3 H-dopamine plus 3 H-3-methoxytyramine newly formed from 3H-Dopa. Amphetamine and apomorphine have no comparable effect.Striatal levels of 3,4-dihydroxyphenylacetic acid are more efficiently lowered by DMT than those of homovanillic acid. The reverse has been observed with apomorphine, whereas amphetamine increases the concentrations of homovanillic acid and decreases those of 3,4-dihydroxyphenylacetic acid.Thus, in addition to its MAO inhibitory action, DMT probably also possesses dopamine-releasing effects. Both these properties could result in an indirect dopaminomimetic activity of DMT. It may be assumed, therefore, that the psychotomimetic activity of this compound is not only linked to its effects on cerebral serotonergic mechanisms, but to a combination of these with an indirect dopaminergic stimulant activity.

Neuropharmacology of N,N-dimethyltryptamine

“…On average a 100 mL dose of ayahuasca contains about 24 mg of DMT (Callaway et al, 1996). Interestingly, DMT is itself a short-acting monoamine oxidase inhibitor at high doses (maximum effects at 50 mg/kg), and is selective for MAO-A (Reimann and Schneider, 1993, Smith et al, 1962; Waldmeier and Maitre, 1977). In these studies, DMT decreased serotonin and dopamine deamination in rat striatum concomitantly with rapid onset (15 min).…”

“…For example, DMT releases dopamine from presynaptic stores (Smith, 1975). This release of dopamine in combination with the effects of MAO causes an indirect dopaminergic stimulant activity (Waldmeier and Maitre, 1977). DMT (20 mg/ml) caused 42% decrease in concentration of dopamine in rat forebrain (5 - 60 min) while norepinephrine was not affected, no change in the levels of the dopamine metabolite homovanillic acid (HVA, a common marker for dopamine levels) was observed in corpus striatum.…”

“…Dopamine steady state concentrations remained unchanged. Further, DMT increased accumulation of 3H DA and 3H 3MT newly formed from 3H DOPA (Waldmeier and Meitre, 1977). 3,4-Dihydroxyphenylacetic acid (DOPAC, a major metabolite of dopamine) more efficiently lowered by DMT rather than HVA (Waldmeier and Meitre, 1977) in the striatum and whole brain.…”

“…Further, DMT increased accumulation of 3H DA and 3H 3MT newly formed from 3H DOPA (Waldmeier and Meitre, 1977). 3,4-Dihydroxyphenylacetic acid (DOPAC, a major metabolite of dopamine) more efficiently lowered by DMT rather than HVA (Waldmeier and Meitre, 1977) in the striatum and whole brain. This is distinct from the effects of classic MAOIs, which decrease both DOPAC and HVA (Maitre et al, 1976; Waldmeier et al, 1976).…”

BEHAVIOURAL CHANGES INDUCED BY N,N‐DIMETHYLTRYPTAMINE IN RODENTS

“…It might, therefore, be argued that DMT causes hyperactivity by a direct action on cerebral dopamine pathways. Indeed, biochemical evidence suggests that DMT alone stimulates dopamine release (Waldmeier & Maitre, 1977;Haubrich & Wang, 1977;Smith, 1977 (von Hungen, Roberts & Hill, 1975). It is therefore difficult to attribute the ability of DMT to induce hyperactivity in rodents to a direct agonist action on either cerebral dopamine or 5-HT receptors.…”