Comparison of the discriminative stimulus effects of dimethyltryptamine with different classes of psychoactive compounds in rats

Abstract

Rationale: There has been increased recreational use of dimethyltryptamine (DMT), but little is known of its discriminative stimulus effects.

Objectives: The present study assessed the similarity of the discriminative stimulus effects of DMT to other types of hallucinogens and to psychostimulants.

Methods: Rats were trained to discriminate DMT from saline. To test the similarity of DMT to known hallucinogens, the ability of (+)-lysergic acid diethylamide (LSD), (-)-2,5-dimethoxy-4-methylamphetamine (DOM), (+)-methamphetamine, or (+/-)3,4-methylenedioxymethyl amphetamine (MDMA) to substitute in DMT-trained rats was tested. The ability of DMT to substitute in rats trained to discriminate each of these compounds was also tested. To assess the degree of similarity in discriminative stimulus effects, each of the compounds was tested for substitution in all of the other training groups.

Results: LSD, DOM, and MDMA all fully substituted in DMT-trained rats, whereas DMT fully substituted only in DOM-trained rats. Full cross-substitution occurred between DMT and DOM, LSD and DOM, and (+)-methamphetamine and MDMA. MDMA fully substituted for (+)-methamphetamine, DOM, and DMT, but only partially for LSD. In MDMA-trained rats, LSD and (+)-methamphetamine fully substituted, whereas DMT and DOM did not fully substitute. No cross-substitution was evident between (+)-methamphetamine and DMT, LSD, or DOM.

Conclusions: DMT produces discriminative stimulus effects most similar to those of DOM, with some similarity to the discriminative stimulus effects of LSD and MDMA. Like DOM and LSD, DMT seems to produce predominately hallucinogenic-like discriminative stimulus effects and minimal psychostimulant effects, in contrast to MDMA which produced hallucinogen- and psychostimulant-like effects.

Fig. 1

Learning curve showing the acquisition of the discrimination between DMT and the saline vehicle. The y-axis shows percentage of responding on the DMT-appropriate lever over 30 saline- and 30 drug-training sessions. Error bars show standard error of the mean. The study began with a DMT training dose of 10 mg/kg. At session 16, the training dose was decreased to 5 mg/kg (at arrow). Data for drug session 7 are missing due to computer malfunction. Following the axis break, the data for those sessions during which each rat met the training criterion is shown as an average of the last 5 saline and 5 drug sessions. Each point represents the average of 15 rats.

Fig. 2

Dose-effect of DMT in rats trained to discriminate DMT from saline. The top panel shows percentage of DMT-appropriate responding over increasing doses of DMT. The bottom panel shows rate of responding in responses per sec. Error bars show standard error of the mean. Ctrl=control points (vehicle alone and DMT 5 mg/kg). Each point represents the average of 15 rats. * indicates points different from the vehicle control.

Fig. 3

Cross-substitution of DMT, DOM, LSD, MDMA, and methamphetamine. Top panels show drug-appropriate responding of the test compounds in DMT-, LSD-, DOM-, MDMA-, and methamphetamine-trained rats. Bottom panels show rate of responding in responses per sec. Each point represents the average of six rats except where shown. * indicates points different from the vehicle control. Meth = methamphetamine.