The indole hallucinogens, N, N-dimethyltryptamine (DMT) and 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT), have different effects from mescaline on rat shuttlebox avoidance

Abstract

The indole hallucinogenic drugs, N, N-dimethyltryptamine (DMT) and 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT), had a different psychopharmacological profile from mescaline on rat shuttlebox avoidance; the differences were strain and/or baseline-dependent. N, N-dimethyltryptamine and 5-MeO-DMT shared dose response disruptive effects with mescaline on avoidance behaviour in two rat strains who were performing the conditioned avoidance response at a high baseline (i.e. during acqusition in Fischer 344s—Experiment 1; on pretrained good performing hooded rats—Experiment 2). N, N-dimethyltryptamine and 5-MeO-DMT were without an effect when the baseline conditioned avoidance response was low (i.e. during acquisition in Zivic-Millers, Hoods or Roman Low Avoiders—Experiment 1; on pretrained poorly performing hooded rats—Experiment 2) but mescaline was facilitatory in these situations. There were strain-related differences in sensitivity to the drugs with Roman High Avoiders insensitive to DMT, 5-MeO-DMT and mescaline, while Fischer 344s were the most sensitive to these three drugs. The relative potency of these three hallucinogens in disrupting avoidance behavior (5-MeO-DMT > DMT > mescaline), in terms of mg/kg paralleled reports of their relative potency on central serotonergic activity. The facilitatory effect produced by mescaline, but not produced by DMT nor 5-MeO-DMT, may be related to the findings that mescaline has a stronger action on the catecholaminergic system than the indoles.