Differences in the stimulus properties of 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine in animals trained to discriminate hallucinogens from saline

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Abstract

The stimulus properties of 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and several related compounds were compared to those of (+)-lysergic acid diethylamide (LSD) and mescaline (3,4,5-trimethoxyphenylethylamine) in a two-lever, water-reinforced, drug discrimination task. In animals trained to discriminate LSD (0.08 mg/kg) from saline (n = 8), LSD-like responding occurred during substitution (generalization) tests with sufficiently high doses of (±)-2,5-dimethoxy-4-methylamphetamine, LSD, mescaline, psilocybin and (-)-MDA; saline appropriate responding occurred after (+)-MDA and both (+)- and (-)-MDMA. In animals trained to discrminate mescaline (10 mg/kg; n = 8), (-)-MDA, (+)-MDA, (-)-MDMA and (+)-MDMA as well as (±)-2,5-dimethoxy-4-methylamphetamine, LSD, mescaline and psilocybin mimicked the training drug. Neither (+)-amphetamine nor cocaine produced mescaline-like responding; fenfluramine substituted partially for mescaline but not LSD. Because all of the phenylisopropylamine enantiomers mimicked the potent hallucinogen mescaline (10 mg/kg), these results do not support suggestions that similarities in the behavioral effects of 'designer' drugs such as MDA and MDMA to those of hallucinogens are limited to (-)-MDA. They also indicate that, although LSD and mescaline may be pharmacologically similar (in other assays), these compounds do not have identical stimulus properties.

Original languageEnglish (US)
Pages (from-to)866-870
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume246
Issue number3
StatePublished - Jan 1 1988
Externally publishedYes

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3,4-Methylenedioxyamphetamine
Mescaline
Hallucinogens
N-Methyl-3,4-methylenedioxyamphetamine
Lysergic Acid Diethylamide
Psilocybin
2,5-Dimethoxy-4-Methylamphetamine
Designer Drugs
Fenfluramine
Amphetamine
Cocaine
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Differences in the stimulus properties of 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine in animals trained to discriminate hallucinogens from saline",
abstract = "The stimulus properties of 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and several related compounds were compared to those of (+)-lysergic acid diethylamide (LSD) and mescaline (3,4,5-trimethoxyphenylethylamine) in a two-lever, water-reinforced, drug discrimination task. In animals trained to discriminate LSD (0.08 mg/kg) from saline (n = 8), LSD-like responding occurred during substitution (generalization) tests with sufficiently high doses of (±)-2,5-dimethoxy-4-methylamphetamine, LSD, mescaline, psilocybin and (-)-MDA; saline appropriate responding occurred after (+)-MDA and both (+)- and (-)-MDMA. In animals trained to discrminate mescaline (10 mg/kg; n = 8), (-)-MDA, (+)-MDA, (-)-MDMA and (+)-MDMA as well as (±)-2,5-dimethoxy-4-methylamphetamine, LSD, mescaline and psilocybin mimicked the training drug. Neither (+)-amphetamine nor cocaine produced mescaline-like responding; fenfluramine substituted partially for mescaline but not LSD. Because all of the phenylisopropylamine enantiomers mimicked the potent hallucinogen mescaline (10 mg/kg), these results do not support suggestions that similarities in the behavioral effects of 'designer' drugs such as MDA and MDMA to those of hallucinogens are limited to (-)-MDA. They also indicate that, although LSD and mescaline may be pharmacologically similar (in other assays), these compounds do not have identical stimulus properties.",
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T1 - Differences in the stimulus properties of 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine in animals trained to discriminate hallucinogens from saline

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AU - Appel, J. B.

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N2 - The stimulus properties of 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and several related compounds were compared to those of (+)-lysergic acid diethylamide (LSD) and mescaline (3,4,5-trimethoxyphenylethylamine) in a two-lever, water-reinforced, drug discrimination task. In animals trained to discriminate LSD (0.08 mg/kg) from saline (n = 8), LSD-like responding occurred during substitution (generalization) tests with sufficiently high doses of (±)-2,5-dimethoxy-4-methylamphetamine, LSD, mescaline, psilocybin and (-)-MDA; saline appropriate responding occurred after (+)-MDA and both (+)- and (-)-MDMA. In animals trained to discrminate mescaline (10 mg/kg; n = 8), (-)-MDA, (+)-MDA, (-)-MDMA and (+)-MDMA as well as (±)-2,5-dimethoxy-4-methylamphetamine, LSD, mescaline and psilocybin mimicked the training drug. Neither (+)-amphetamine nor cocaine produced mescaline-like responding; fenfluramine substituted partially for mescaline but not LSD. Because all of the phenylisopropylamine enantiomers mimicked the potent hallucinogen mescaline (10 mg/kg), these results do not support suggestions that similarities in the behavioral effects of 'designer' drugs such as MDA and MDMA to those of hallucinogens are limited to (-)-MDA. They also indicate that, although LSD and mescaline may be pharmacologically similar (in other assays), these compounds do not have identical stimulus properties.

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