Lorazepam and pentobarbital drug discrimination in baboons: cross-drug generalization and interaction with Ro 15-1788. 1983

N A Ator, and R R Griffiths

Four baboons were trained to discriminate lorazepam (1.0 mg/kg i.m.) and two baboons were trained to discriminate pentobarbital (5.6 mg/kg i.m.) in a two-lever drug discrimination procedure. Food delivery depended on 20 consecutive responses on one lever in sessions preceded by an injection of the training drug and on 20 consecutive responses on the other lever after no drug. All baboons reliably completed 100% of the response runs on the appropriate lever in training sessions. Test sessions were conducted in which a drug dose different from the training dose was injected and 20 consecutive responses on either lever produced food. Drug lever responding occurred after a range of lorazepam and diazepam doses in both lorazepam- and pentobarbital-trained baboons. Drug lever responding also occurred after a range of doses of pentobarbital in the pentobarbital-trained baboons but in only one of the four lorazepam-trained baboons. Ro 15-1788 (0.1-1.0 mg/kg p.o.) antagonized the effect of lorazepam but had no effect on the pentobarbital discriminative stimulus. The asymmetrical generalization with lorazepam and pentobarbital suggests a specificity of discriminative stimulus effects that heretofore have not been documented in drug discrimination experiments with benzodiazepines and barbiturates. The selective antagonism of lorazepam by the benzodiazepine-receptor antagonist Ro 15-1788 suggests that the lorazepam but not the pentobarbital discriminative stimulus is mediated at the benzodiazepine receptor.

UI MeSH Term Description Entries
D008140 Lorazepam A benzodiazepine used as an anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent. Apo-Lorazepam,Ativan,Donix,Duralozam,Durazolam,Idalprem,Laubeel,Lorazep Von Ct,Lorazepam Medical,Lorazepam-Neuraxpharm,Lorazepam-Ratiopharm,Novo-Lorazem,Nu-Loraz,Orfidal Wyeth,Sedicepan,Sinestron,Somagerol,Temesta,Tolid,Témesta,WY-4036,Apo Lorazepam,Lorazepam Neuraxpharm,Lorazepam Ratiopharm,Medical, Lorazepam,Novo Lorazem,Nu Loraz,Von Ct, Lorazep,WY 4036,WY4036,Wyeth, Orfidal
D008297 Male Males
D010215 Papio A genus of the subfamily CERCOPITHECINAE, family CERCOPITHECIDAE, consisting of five named species: PAPIO URSINUS (chacma baboon), PAPIO CYNOCEPHALUS (yellow baboon), PAPIO PAPIO (western baboon), PAPIO ANUBIS (or olive baboon), and PAPIO HAMADRYAS (hamadryas baboon). Members of the Papio genus inhabit open woodland, savannahs, grassland, and rocky hill country. Some authors consider MANDRILLUS a subgenus of Papio. Baboons,Baboons, Savanna,Savanna Baboons,Baboon,Baboon, Savanna,Papios,Savanna Baboon
D010424 Pentobarbital A short-acting barbiturate that is effective as a sedative and hypnotic (but not as an anti-anxiety) agent and is usually given orally. It is prescribed more frequently for sleep induction than for sedation but, like similar agents, may lose its effectiveness by the second week of continued administration. (From AMA Drug Evaluations Annual, 1994, p236) Mebubarbital,Mebumal,Diabutal,Etaminal,Ethaminal,Nembutal,Pentobarbital Sodium,Pentobarbital, Monosodium Salt,Pentobarbitone,Sagatal,Monosodium Salt Pentobarbital
D003975 Diazepam A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity. 7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,Apaurin,Diazemuls,Faustan,Relanium,Seduxen,Sibazon,Stesolid,Valium
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
D005442 Flumazenil A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses. Flumazepil,Anexate,Lanexat,Ro 15-1788,Romazicon,Ro 15 1788,Ro 151788
D005794 Generalization, Response The principle that after an organism learns to respond in a particular manner to a stimulus, that stimulus is effective in eliciting similar responses. Generalizations, Response,Response Generalization,Response Generalizations

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