Effects of some phenylethylamines in rhesus monkeys trained to discriminate (+)-amphetamine from saline.

Abstract

Although the structure-activity relationships (SAR) for the discriminative stimulus (DS) effects of phenylethylamines (PEAs) have been extensively evaluated in rats, only isolated components of the SAR have been studied in other species. Since DS effects in animals predict subjective effects in humans, it is important to establish cross-species generality of substitution results. In the present experiment, rhesus monkeys (n = 4) were trained to discriminate (+)-amphetamine (0.56 or 1.0 mg/kg, i.g.) from saline in a two-lever drug discrimination paradigm. Responding was maintained under a fixed-ratio discrete-trials schedule of shock avoidance. (+)-Amphetamine, and the N-substituted phenylethylamines (+)-methylamphetamine, and (+)-ethylamphetamine all engendered dose-dependent, full substitution for (+)-amphetamine and had no effect on rate of responding. In contrast, the ring-substituted compounds (+/-)-4-methoxyamphetamine (PMA), (+/-)-2,5-dimethoxy-4-methylamphetamine (DMA), (+/-)-2,5-dimethoxy-4-methylamphetamine (DOM), and (+/-)-3,4, 5-trimethoxyamphetamine (TMA) occasioned little or no (+)-amphetamine-appropriate response up to doses of 3.0 or 10 mg/kg. Therefore, it appears that monkeys respond to N-substituted amphetamines in the same way as rats, at least qualitatively. Considering that ring-substituted compounds have been found to partially substitute for (+)-amphetamine in rats, it is possible that the (+)-amphetamine DS may be pharmacologically more selective in monkeys. However, methodological differences may also explain differences between experiments.