The effects of 2,5-dimethoxy-4-methylamphetamine (DOM), 2,5-dimethoxy-4-ethylamphetamine (DOET), d-amphetamine, and cocaine in rats trained with mescaline as a discriminative stimulus

Mescaline can serve as a discriminative stimulus in rats, allowing them to distinguish it from saline. This study tested whether other drugs produce similar internal cues. The hallucinogens DOM and DOET, at 0.3 mg/kg, fully mimicked mescaline's discriminative effects, while d-amphetamine and cocaine did not, even at doses that otherwise controlled behavior. When DOET was substituted for saline as the non-drug cue, rats failed to learn the discrimination over 50 sessions. The findings suggest that the stimulus properties of mescaline in rats correspond more closely to pre-hallucinogenic LSD-like activity in humans than to hallucinogenic activity itself, indicating these effects are necessary but not sufficient for predicting human hallucinogenic potential.

Study at a glance

Abstract

The effects of mescaline (3,4,5-trimethoxyphenylethylamine), a hallucinogen, can function as a discriminative stimulus in appropriately trained rats. As a test of the hypothesis that those pharmacologic properties which distinguish hallucinogens and non-hallucinogens in man are reflected in distinctive stimuli in rats, the present experiments examined the effects of 2,5-dimethoxy-4-methylamphetamine (DOM), 2,5-dimethoxy-4-ethylamphetamine (DOET), d-amphetamine, and cocaine in rats trained with mescaline as a discriminative stimulus. Administration of a range of doses of DOM and DOET to subjects in which saline functioned as SD and mescaline as Sdelta revealed that a dose of 0.3 mg of either DOM or DOET was equivalent to the training dose of mescaline. When tested in rats in which mescaline served as SD, DOM and DOET were likewise found to mimic mescaline. In contrast, doses of d-amphetamine and cocaine (1 and 30 mg/kg, respectively) which were equivalent to the training dose of mescaline as Sdelta, did not result in responding appropriate for the mescaline condition when mescaline was trained as SD. When DOET (0.3 mg/kg) was substituted for saline as Sdelta, no evidence of discriminated responding was obtained in the course of 50 sessions. The present data, in conjunction with previous observations, suggest that those effects of mescaline in the rat which function as a discriminative stimulus are better correlated with pre-hallucinogenic LSD-like activity in man then with hallucinogenic activity per se. Thus, these effects in rats represent a necessary but not a sufficient condition for prediction of hallucinogenic activity in man.