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Further studies on N-methyl-1(3, 4-methylenedioxyphenyl)-2-aminopropane as a discriminative stimulus: Antagonism by 5-hydroxytryptamine3 antagonists

Glennon, R.A. ; Higgs, R. ; Young, R. ; Issa, H. ;
  • 초록  

    Using a standard two-lever operant paradigm, male Sprague-Dawley rats were trained to discriminate 1.5 mg/kg N-methyl-1(3,4-methylenedioxyph enyl)-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-hydroxytryptamine 1A (5-HT 1A ) antagonist NAN-190, the 5-HT 2 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-HT 3 antagonists zacopride and LY 278544 (ID 50 = 0.02 μg/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 complex mechanism involving both dopaminergic and serotonergic components.


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  • 주제어

    MDMA .   Drug discrimination .   5-HT2 .   5-HT3 .   Dopamine .   Pirenperone .   Zacopride .   LY 278584 .   DOM .   Amphetamine.  

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