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Further studies on N-methyl-1(3,4-methylenedioxyphenyl)-2-aminopropane as a discriminative stimulus: antagonism by 5-hydroxytryptamine3 antagonists.
Pharmacol Biochem Behav. 1992 Dec; 43(4):1099-106.PB

Abstract

Using a standard two-lever operant paradigm, male Sprague-Dawley rats were trained to discriminate 1.5 mg/kg N-methyl-1(3,4-methylenedioxyphenyl)-2- aminopropane (MDMA) from saline using a variable-interval 15-s schedule of reinforcement for food reward. Tests of stimulus antagonism were conducted to further define the mechanism of action of MDMA as a discriminative stimulus. Low doses of the 5-hydroxytryptamine1A (5-HT1A) antagonist NAN-190, the 5-HT2 antagonist pirenperone, and the dopamine antagonist haloperidol were able to somewhat attenuate the MDMA stimulus; however, none of these agents decreased MDMA-appropriate responding to less than 46%. The 5-HT3 antagonists zacopride and LY 278584 (ID50 = 0.02 micrograms/kg) antagonized the MDMA discriminative stimulus. Zacopride also attenuated the stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in DOM-trained animals but not those of (+)amphetamine in (+)amphetamine-trained animals. Several possible mechanistic interpretations are provided but it is concluded that MDMA produces its stimulus effects via a complex mechanism involving both dopaminergic and serotonergic components.

Authors+Show Affiliations

Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0540.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

1361990

Citation

Glennon, R A., et al. "Further Studies On N-methyl-1(3,4-methylenedioxyphenyl)-2-aminopropane as a Discriminative Stimulus: Antagonism By 5-hydroxytryptamine3 Antagonists." Pharmacology, Biochemistry, and Behavior, vol. 43, no. 4, 1992, pp. 1099-106.
Glennon RA, Higgs R, Young R, et al. Further studies on N-methyl-1(3,4-methylenedioxyphenyl)-2-aminopropane as a discriminative stimulus: antagonism by 5-hydroxytryptamine3 antagonists. Pharmacol Biochem Behav. 1992;43(4):1099-106.
Glennon, R. A., Higgs, R., Young, R., & Issa, H. (1992). Further studies on N-methyl-1(3,4-methylenedioxyphenyl)-2-aminopropane as a discriminative stimulus: antagonism by 5-hydroxytryptamine3 antagonists. Pharmacology, Biochemistry, and Behavior, 43(4), 1099-106.
Glennon RA, et al. Further Studies On N-methyl-1(3,4-methylenedioxyphenyl)-2-aminopropane as a Discriminative Stimulus: Antagonism By 5-hydroxytryptamine3 Antagonists. Pharmacol Biochem Behav. 1992;43(4):1099-106. PubMed PMID: 1361990.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Further studies on N-methyl-1(3,4-methylenedioxyphenyl)-2-aminopropane as a discriminative stimulus: antagonism by 5-hydroxytryptamine3 antagonists. AU - Glennon,R A, AU - Higgs,R, AU - Young,R, AU - Issa,H, PY - 1992/12/1/pubmed PY - 1992/12/1/medline PY - 1992/12/1/entrez SP - 1099 EP - 106 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol Biochem Behav VL - 43 IS - 4 N2 - Using a standard two-lever operant paradigm, male Sprague-Dawley rats were trained to discriminate 1.5 mg/kg N-methyl-1(3,4-methylenedioxyphenyl)-2- aminopropane (MDMA) from saline using a variable-interval 15-s schedule of reinforcement for food reward. Tests of stimulus antagonism were conducted to further define the mechanism of action of MDMA as a discriminative stimulus. Low doses of the 5-hydroxytryptamine1A (5-HT1A) antagonist NAN-190, the 5-HT2 antagonist pirenperone, and the dopamine antagonist haloperidol were able to somewhat attenuate the MDMA stimulus; however, none of these agents decreased MDMA-appropriate responding to less than 46%. The 5-HT3 antagonists zacopride and LY 278584 (ID50 = 0.02 micrograms/kg) antagonized the MDMA discriminative stimulus. Zacopride also attenuated the stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in DOM-trained animals but not those of (+)amphetamine in (+)amphetamine-trained animals. Several possible mechanistic interpretations are provided but it is concluded that MDMA produces its stimulus effects via a complex mechanism involving both dopaminergic and serotonergic components. SN - 0091-3057 UR - https://www.unboundmedicine.com/medline/citation/1361990/Further_studies_on_N_methyl_1_34_methylenedioxyphenyl__2_aminopropane_as_a_discriminative_stimulus:_antagonism_by_5_hydroxytryptamine3_antagonists_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0091-3057(92)90488-2 DB - PRIME DP - Unbound Medicine ER -