alpha-Ethyltryptamine (alpha-ET) as a discriminative stimulus in rats.
alpha-Ethyltryptamine (etryptamine, alpha-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 alpha-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 alpha-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 alpha-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 alpha-ET stimulus generalized to S(-)alpha-ET (ED(50)=1.6 mg/kg) and R(+)alpha-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 alpha-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 alpha-ET produces a complex stimulus.
Glennon
Richard A
RA
Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0540, USA. glennon@vcu.edu
Bondareva
Tatiana
T
Young
Richard
R
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005795:Generalization, Stimulus / Q000187:drug effects*; D008297:Male; D019904:Polymethyl Methacrylate / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014363:Tryptamines / Q000494:pharmacology*
D014363:Tryptamines; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D019904:Polymethyl Methacrylate; D000661:Amphetamine; C038034:etryptamine