Discriminative stimulus properties of a-ethyltryptamine optical isomers$

a-Ethyltryptamine (a-ET) possesses central stimulant and hallucinogenic activity. Also, in tests of stimulus generalization using rats trained to discriminate the controlled substance analog (i.e., designer drug) N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) from vehicle, a-ET substituted for MDMA. These previous studies employed racemic a-ET. Because psychoactive phenylalkylamines with abuse potential can produce one or more of three distinct stimulus effects (i.e., amphetamine-, DOM- and/or PMMA-like effects) in animals trained to discriminate either the stimulant (+)amphetamine, the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), or N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA) from vehicle, and because these effects can be stereoselective, the individual optical isomers of a-ET were examined in groups of animals trained to discriminate (+)amphetamine, DOM, PMMA and MDMA from saline vehicle. ( )a-ET (ED50 = 7.8 mg/kg), but not (+)a-ET (maximum of 53 % drug-appropriate responding), substituted for (+)amphetamine, whereas (+)a-ET (ED50 = 2.7 mg/kg), but not ( )a-ET (maximum of 33 % drug-appropriate responding), substituted for DOM. Both optical isomers of a-ET substituted for PMMA and MDMAwith ED50 values of 1.6 and 1.4 mg/kg (PMMA-trained animals) and 1.3 and 2.0 mg/kg (MDMA-trained animals) for ( )a-ET and (+)a-ET, respectively. The results of this investigation suggest that both optical isomers of a-ET are capable of producing an MDMA/PMMA-like effect at nearly comparable doses, and that the stimulant or amphetamine-like nature of a-ET resides primarily with its ( )isomer whereas hallucinogenic or DOM-lik