BEHAVIOURAL CHANGES INDUCED BY N,N‐DIMETHYLTRYPTAMINE IN RODENTS

Abstract

I N,N-Dimethyltryptamine (DMT) in pargyline pretreated rodents induced a dose-dependent behavioural syndrome consisting of hyperactivity, prostration and hindlimb abduction, mild tremor, Straub tail, retropulsion and jerking. 2 In rats pretreated with pargyline, the behavioural syndrome induced by DMT differed from that induced by L-tryptophan or quipazine, in the lack of forepaw treading and head-weaving and in the presence of only mild tremor. 3 The hyperactivity component of the DMT-induced behavioural syndrome in pargyline-pretreated mice was potentiated by cyproheptadine, methergoline, and mianserin, inhibited by cinanserin, haloperidol, pimozide, methiothepin and propranolol, and not affected by 501C67-sulphate and methysergide. 4 The maximal behavioural changes induced by DMT in rats, other than hyperactivity, were unaffected by pretreatment with cyproheptadine, methysergide, and cinanserin. However, propranolol reduced the intensity of all behavioural effects apart from body jerking, and methergoline decreased the duration of prostration. Phenoxybenzamine and haloperidol, in contrast, enhanced prostration. 5 DMT plus pargyline did not induce circling behaviour in mice with a unilateral 6-hydroxydopamine lesion of the nigro-striatal pathway. 6 The DMT-induced behavioural syndrome appears to consist of two components, (a) hyperactivity and (b) other behavioural changes. They differ in their response to drugs affecting brain monoamines. The hyperactivity component may be expressed via dopamine mechanisms, but the other behavioural changes are not. The two behaviours do not respond consistently to drugs believed to alter brain 5-hydroxytryptamine function.

The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator

“…On the basis of these findings, which were discovered before sigma receptor identification, DMT has been hypothesized to act through an unknown “hallucinogen” receptor (8). We confirmed results (28) that intraperitoneal (ip) administration of DMT (2 mg per kilogram of body weight) 2 hours after pargyline (75 mg/kg, ip) injection induced hypermobility in WT mice (7025 ± 524.1 cm, n = 12 WT mice) in an open-field assay. Identical drug treatments in sigma-1 receptor KO mice had no hypermobility action (2328 ± 322.9 cm, n = 12 KO mice, P < 0.0001; Fig.…”

“…DMT injection induces hypermobility in rodents concurrently treated with the monoamine oxidase inhibitor pargyline (28), and this action is not antagonized by blockers of dopamine or serotonin receptors, but is potently inhibited by haloperidol (28). Although haloperidol is thought to act in part through the dopamine D 2 receptor system, it is also a potent sigma-1 receptor agonist [sigma-1 inhibition constant ( K i ) = 3 nM (29); sigma-2 K i = 54 nM (29)] when inhibiting voltage-gated ion channels (5, 25).…”

In Vivo Long-Term Kinetics of Radiolabeled N,N-Dimethyltryptamine and Tryptamine

“…Some DMT behavior did not involve the 5-HT or other monoaminergic systems (29), and the DMT-enhanced phosphatidylinositol production was not blocked by the 5-HT 2A receptor antagonist ketanserin (30). Therefore, 5-HT receptors are not the sole mediators of DMT psychodysleptic effects.…”

Neuropharmacology of N,N-dimethyltryptamine

“…These findings will be discussed in more detail in the paragraph on cardiovascular effects in section 5. Mild cross-tolerance to DMT was reported in humans made tolerant to LSD (Rosenberg et al, 1964; Jenner et al, 1980). Taken together, these findings suggest that tolerance can develop to the cardiovascular and other peripheral effects of DMT, although little or no tolerance develops to the subjective effects.…”

“…Although the serotonin system has been thought to be the main contributor to the psychedelic effects of DMT, other behavioral effects have been observed which do not involve the serotonin or other monoaminergic systems; such as jerking, retropulsion, and tremors (Deliganis et al, 1991; Jenner et al, 1980). In addition, molecular effects of DMT have been identified that are not mediated by serotonin receptors.…”