Opiate agonist-antagonist interactions: application of a three-key drug discrimination procedure. 1985

C P France, and J H Woods

Pigeons were trained to discriminate among i.m. injections of morphine (5.6 mg/kg), saline and naltrexone (10.0 mg/kg) in a three-key operant procedure with food reinforcement. Animals acquired the discrimination; each training condition occasioned responding on the injection-appropriate key, and the effects of morphine and naltrexone were dose-dependent. The opiate agonists ethylketazocine, buprenorphine and pentazocine substituted completely for morphine, and the opiate antagonist naloxone substituted completely for naltrexone. Meperidine, dextrorphan, beta-funaltrexamine, diprenorphine and nalorphine produced responding predominantly on the saline key, indicating that these compounds do not share completely discriminative properties with naltrexone or morphine in the pigeon. Small doses of naltrexone (0.01 and 0.1 mg/kg) shifted the morphine discrimination dose-effect curve in parallel to the right, without producing naltrexone-appropriate responding. Larger doses of naltrexone (1.0-10.0 mg/kg) prevented the discriminative effect of morphine and generated dose-dependent naltrexone-appropriate responding. The prior administration of small doses of morphine (0.1 and 1.0 mg/kg) enhanced the discriminative effects of naltrexone. Some dose combinations of naltrexone and morphine produced responding on all three keys, up to doses that suppressed behavior. The study of agonist-antagonist interactions may be aided by the use of these procedures, as descriptions of insurmountable antagonism may be complemented by the identification of stimulus conditions associated with the antagonist, as well as those conditions that represent novel stimulus states.

UI MeSH Term Description Entries
D009020 Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D009271 Naltrexone Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. Antaxone,Celupan,EN-1639A,Nalorex,Naltrexone Hydrochloride,Nemexin,ReVia,Trexan,EN 1639A,EN1639A
D009292 Narcotic Antagonists Agents inhibiting the effect of narcotics on the central nervous system. Competitive Opioid Antagonist,Narcotic Antagonist,Opioid Antagonist,Opioid Antagonists,Opioid Receptor Antagonist,Opioid Reversal Agent,Competitive Opioid Antagonists,Opioid Receptor Antagonists,Opioid Reversal Agents,Agent, Opioid Reversal,Agents, Opioid Reversal,Antagonist, Competitive Opioid,Antagonist, Narcotic,Antagonist, Opioid,Antagonist, Opioid Receptor,Antagonists, Competitive Opioid,Antagonists, Narcotic,Antagonists, Opioid,Antagonists, Opioid Receptor,Opioid Antagonist, Competitive,Opioid Antagonists, Competitive,Receptor Antagonist, Opioid,Receptor Antagonists, Opioid,Reversal Agent, Opioid,Reversal Agents, Opioid
D009294 Narcotics Agents that induce NARCOSIS. Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. They are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS. Analgesics, Narcotic,Narcotic Analgesics,Narcotic,Narcotic Effect,Narcotic Effects,Effect, Narcotic,Effects, Narcotic
D010856 Columbidae Family in the order COLUMBIFORMES, comprised of pigeons or doves. They are BIRDS with short legs, stout bodies, small heads, and slender bills. Some sources call the smaller species doves and the larger pigeons, but the names are interchangeable. Columba livia,Doves,Pigeons,Domestic Pigeons,Feral Pigeons,Rock Doves,Rock Pigeons,Domestic Pigeon,Dove,Dove, Rock,Doves, Rock,Feral Pigeon,Pigeon,Pigeon, Domestic,Pigeon, Feral,Pigeon, Rock,Pigeons, Domestic,Pigeons, Feral,Pigeons, Rock,Rock Dove,Rock Pigeon
D004193 Discrimination Learning Learning that is manifested in the ability to respond differentially to various stimuli. Discriminative Learning,Discrimination Learnings,Discriminative Learnings,Learning, Discrimination,Learning, Discriminative
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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