Cocaine--stimulus generalization to MDA optical isomers: a reevaluation.
It has already been demonstrated that the psychoactive agent 1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDA) produces effects that are both hallucinogen-like and amphetamine or stimulant-like in animals. Hallucinogenic activity is associated primarily with the R(-)-isomer of MDA whereas stimulant activity is primarily associated with the S(+)-isomer. Because a previous report indicates that S(+)MDA fails to substitute for cocaine in rats trained to discriminate cocaine from vehicle, and because these findings are inconsistent with the purported stimulant nature of S(+)MDA, we reinvestigated the effect of both MDA isomers in rats. In this investigation, S(+)MDA doses of 1.25 and 1.5 mg/kg were found to produce > 80% cocaine-appropriate responding in rats trained to discriminate 8 mg/kg of cocaine from saline. However, consistent with a previous report, R(-)MDA resulted only in partial generalization. These new results support the hypothesis that the optical isomers of MDA produce distinguishable stimulus effects in rats and that S(+)MDA is the more stimulant isomer of MDA.
Young
R
R
Department of Medicinal Chemistry, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
Glennon
R A
RA
D015104:3,4-Methylenedioxyamphetamine / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D004193:Discrimination Learning; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005795:Generalization, Stimulus; D006213:Hallucinogens / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D000697:Central Nervous System Stimulants; D006213:Hallucinogens; D015104:3,4-Methylenedioxyamphetamine; D003042:Cocaine