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A three-lever operant procedure differentiates the stimulus effects of R(-)-MDA from S(+)-MDA.
J Pharmacol Exp Ther. 1996 Feb; 276(2):594-601.JP

Abstract

1-(3,4-Methylenedioxyphenyl)-2-aminopropane (MDA) produces an effect in humans that is somewhat similar to both a hallucinogen and a central stimulant. We have previously shown that R(-)-MDA but not S(+)-MDA produces a stimulus effect in animals similar to that of the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), whereas S(+)-MDA but not R(-)-MDA produces a stimulus effect similar to that of the stimulant amphetamine. Others have suggested that the stimulus effects of the two MDA isomers may be much more similar than our results would indicate. To help clarify this issue, we have shown that rats (n = 8) can be trained to discriminate 1.25 mg/kg of R(-)-MDA (ED50 = 0.99 mg/kg) from 1.25 mg/kg of S(+)-MDA (ED50 = 0.80 mg/kg) versus 0.9% saline with use of a three-lever operant procedure. To accomplish this task it was necessary to institute a separation of 4 days between injections of the isomers. In tests of stimulus substitution, the administration of various doses of DOM (ED50 = 0.47 mg/kg), S(+)-DOM (ED50 = 2.23 mg/kg) and mescaline (ED50 = 16.04 mg/kg) produced dose-related responding on the R(-)-MDA-appropriate lever. In contrast, the injection of various doses of S(+)-amphetamine (ED50 = 0.46 mg/kg) and cocaine (ED50 = 6.40 mg/kg) produced dose-related responding on the S(+)-MDA-appropriate lever. The administration of racemic MDA, at twice the isomer training dose, resulted in the animals dividing their responses closely between the R(-)-MDA- and S(+)-MDA-designated levers. In antagonism tests, the serotonin-2 antagonist pirenperone blocked the stimulus effect of 1.25 mg/kg of R(-)-MDA but had no effect on the stimulus effect of 1.25 mg/kg of S(+)-MDA. Taken together, these data support the contention that each optical isomer of MDA can produce a markedly different stimulus effect.

Authors+Show Affiliations

Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8632326

Citation

Young, R, and R A. Glennon. "A Three-lever Operant Procedure Differentiates the Stimulus Effects of R(-)-MDA From S(+)-MDA." The Journal of Pharmacology and Experimental Therapeutics, vol. 276, no. 2, 1996, pp. 594-601.
Young R, Glennon RA. A three-lever operant procedure differentiates the stimulus effects of R(-)-MDA from S(+)-MDA. J Pharmacol Exp Ther. 1996;276(2):594-601.
Young, R., & Glennon, R. A. (1996). A three-lever operant procedure differentiates the stimulus effects of R(-)-MDA from S(+)-MDA. The Journal of Pharmacology and Experimental Therapeutics, 276(2), 594-601.
Young R, Glennon RA. A Three-lever Operant Procedure Differentiates the Stimulus Effects of R(-)-MDA From S(+)-MDA. J Pharmacol Exp Ther. 1996;276(2):594-601. PubMed PMID: 8632326.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A three-lever operant procedure differentiates the stimulus effects of R(-)-MDA from S(+)-MDA. AU - Young,R, AU - Glennon,R A, PY - 1996/2/1/pubmed PY - 1996/2/1/medline PY - 1996/2/1/entrez SP - 594 EP - 601 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 276 IS - 2 N2 - 1-(3,4-Methylenedioxyphenyl)-2-aminopropane (MDA) produces an effect in humans that is somewhat similar to both a hallucinogen and a central stimulant. We have previously shown that R(-)-MDA but not S(+)-MDA produces a stimulus effect in animals similar to that of the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), whereas S(+)-MDA but not R(-)-MDA produces a stimulus effect similar to that of the stimulant amphetamine. Others have suggested that the stimulus effects of the two MDA isomers may be much more similar than our results would indicate. To help clarify this issue, we have shown that rats (n = 8) can be trained to discriminate 1.25 mg/kg of R(-)-MDA (ED50 = 0.99 mg/kg) from 1.25 mg/kg of S(+)-MDA (ED50 = 0.80 mg/kg) versus 0.9% saline with use of a three-lever operant procedure. To accomplish this task it was necessary to institute a separation of 4 days between injections of the isomers. In tests of stimulus substitution, the administration of various doses of DOM (ED50 = 0.47 mg/kg), S(+)-DOM (ED50 = 2.23 mg/kg) and mescaline (ED50 = 16.04 mg/kg) produced dose-related responding on the R(-)-MDA-appropriate lever. In contrast, the injection of various doses of S(+)-amphetamine (ED50 = 0.46 mg/kg) and cocaine (ED50 = 6.40 mg/kg) produced dose-related responding on the S(+)-MDA-appropriate lever. The administration of racemic MDA, at twice the isomer training dose, resulted in the animals dividing their responses closely between the R(-)-MDA- and S(+)-MDA-designated levers. In antagonism tests, the serotonin-2 antagonist pirenperone blocked the stimulus effect of 1.25 mg/kg of R(-)-MDA but had no effect on the stimulus effect of 1.25 mg/kg of S(+)-MDA. Taken together, these data support the contention that each optical isomer of MDA can produce a markedly different stimulus effect. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8632326/A_three_lever_operant_procedure_differentiates_the_stimulus_effects_of_R____MDA_from_S_+__MDA_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8632326 DB - PRIME DP - Unbound Medicine ER -