α-Ethyltryptamine (α-ET) as a discriminative stimulus in rats

Abstract

α-Ethyltryptamine (etryptamine, α-ET) is a drug of abuse that first appeared on the clandestine market in the mid-1980s. Its pharmacological actions are poorly understood. In this investigation, it is reported for the first time that α-ET serves as a training drug in drug discrimination studies. Male Sprague–Dawley rats were trained to discriminate (30-min pretreatment time) 2.5 mg/kg of α-ET (ED 50 = 1.3 mg/kg) from saline vehicle using a standard two-lever operant paradigm and a VI-15s schedule of reinforcement for appetitive reward. Once established, the α-ET stimulus was shown to have an onset to action of 30 min and a duration of effect of at least 4 h. In tests of stimulus generalization (substitution), the α-ET stimulus generalized to S(−)α-ET (ED 50 = 1.6 mg/kg) and R(+)α-ET (ED 50 = 1.3 mg/kg). Tests of stimulus generalization were also conducted with prototypical phenylisopropylamines: (+)amphetamine, 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), and N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA). The α-ET stimulus generalized to DOM (ED 50 = 0.4 mg/kg) and PMMA (ED 50 = 0.7 mg/kg), but only partially generalized ( ca. 40% maximal drug-appropriate responding) to (+)amphetamine. The results suggest that α-ET produces a complex stimulus.