Further studies on N-methyl-1(3,4-methylenedioxyphenyl)-2-aminopropane as a discriminative stimulus: antagonism by 5-hydroxytryptamine3 antagonists.
Richard A Glennon, R Higgs, R Young, H Issa
Pharmacology, biochemistry, and behavior December 1992 DOI: 10.1016/0091-3057(92)90488-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal discrimination study Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats |
| Interventions | MDMA NAN-190 pirenperone haloperidol zacopride LY 278584 DOM (+)amphetamine |
| Dose | 1.5 mg/kg MDMA; 0.02 micrograms/kg LY 278584 (ID50) |
| Key points | The 5-HT3 antagonists zacopride and LY 278584 (ID50 = 0.02 micrograms/kg) antagonized the MDMA discriminative stimulus, while low doses of NAN-190, pirenperone, and haloperidol only partially attenuated it (never below 46% MDMA-appropriate responding). Zacopride also attenuated the DOM cue but not the amphetamine cue. The authors conclude that MDMA produces its stimulus effects via a complex mechanism involving both dopaminergic and serotonergic components. |
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.