Hong SS, Young R, Glennon RA (2001) Discriminative stimulus properties of alpha-ethyltryptamine optical isomers. Pharmacol Biochem Behav 70: 311-6.
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Four separate drug-discrimination studies were conducted in rats with (+)-aET and (-)-alphaET serving as the training drugs. (alpha-ET is a tryptamine similar to AMT, and it has been reportedly sold as ecstasy. Separate groups of rats were trained to discriminate either i.p. (+)-amphetamine, DOM, racemic MDMA and racemic PMMA from saline. Only those rats that responded via drug-appropriate lever 80% of the time or greater were given test-drug trials. 1.5 mg/kg MDMA was used in MDMA training trials. Test drug given to MDMA-trained rats were 0.5, 1.5, 3 and 4 mg/kg (-)alpha-ET and 1.5, 2.0, 2.25, and 3.0 mg/kg (+)alpha-ET. Amphetamine stimulus generalized to (+)-aET, but not (-)a-ET, and DOM stimulus generalized to (-)alpha-ET, and not (+)a-ET. However, the MDMA stimulus generalized to both enantiomers of alpha-ET, with over 90% of MDMA-appropriate lever response after (+)-a-ET and (-)-alpha-ET. Potency of stimulus generalization from MDMA was only slightly higher for the "minus" enantiomer of alpha-ET. Both enantiomers also generalized to PMMA. When taken together, these findings suggest that racemic alpha-ET is comparable to racemic MDA in having mixed psychostimulant, hallucinogen, and other (entactogen?) activity. Alpha-ET is now a Schedule I controlled substance, but was briefly marketed as an antidepressant in the early 1960s. It has subsequently appeared as an illicit drug, with reported activity reminiscent of MDA, and has occasionally been sold as "ecstasy." Nichols and colleagues have shown that alpha-ET can induce long-term decreases in serotonergic markers, similar to that produced by MDMA. Geyer and colleagues have shown that alpha-ET produces a pattern of behavioral activation similar to that produced by MDMA in rats. This seems to be the first indolalkylamine (rather than phenethylamine) reported to have MDMA-like effects. Assuming that the MDMA-like discriminative stimulus identified by the rats in each of the enantiomers is related to the feelings increased of sociability, empathy, and introspection reported by humans (this assumption may not be true as drug discrimination research has led to several "false positives"), alpha-ET may prove useful in determining the neurochemical mechanisms of entactogen effects.