Discriminative stimulus functions of CNS sedative drugs assessed by drug versus drug discrimination procedures in gerbils. 1998

T U Järbe, and M D Swedberg
Department of Psychology, University of Uppsala, Faculty of Social Sciences, Sweden.

This study is concerned with dissecting out differences in the discriminative stimulus attributes between drugs from broader pharmacological categories such as sedative/hypnotics where generalization tests often indicate shared stimulus effects. To this end, the discriminative stimulus effects of three to five doses of either chlordiazepoxide (CDP), chlormethiazole (CMZ), ethanol (ETOH), and pentobarbital (P-barb) were studied with gerbils in a two-choice, T-maze task. When the discrimination was based upon the presence versus the absence of drug administration, speed of acquiring the discrimination increased dose-dependently for all four drugs with log of sessions to criterion being a linear function of log dose. The slopes of all four lines were similar. The acquisition of a discrimination based on different doses of the training drug was then examined. A two-to-one ratio of high to low doses was used. Discriminative control developed with CMZ, ETOH, and P-barb, but not with CDP. The side of the T-maze that correlated with the lower training dose was always selected in tests with saline. Gerbils were then trained to discriminate between two drugs using at least two different dose combinations. The CDP versus CMZ, CDP versus ETOH, CMZ versus P-barb, CMZ versus ETOH discriminations were acquired. The CDP versus P-barb discrimination was obtained across doses only after an additional training procedure was instituted such that the P-barb dose was incremented gradually from low to higher doses during discrimination training; the CDP training doses were 20 and 30 mg/kg in two different groups of gerbils, respectively and the dose of P-barb was incremented by 2.5 mg/kg until the final dose of 20 mg/kg was reached with the barbiturate. Thus, although often shown to share similar stimulus effects, members of the broad pharmacological class of CNS sedatives/hypnotics nonetheless were shown to be discriminable from one another. Non-drug tests (vehicle) were used to assess stimulus control between pairs of drugs, equal control being implicated when responding was evenly distributed across the two training conditions.

UI MeSH Term Description Entries
D008297 Male Males
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
D002492 Central Nervous System Depressants A very loosely defined group of drugs that tend to reduce the activity of the central nervous system. The major groups included here are ethyl alcohol, anesthetics, hypnotics and sedatives, narcotics, and tranquilizing agents (antipsychotics and antianxiety agents). CNS Depressants,Depressants, CNS
D002707 Chlordiazepoxide An anxiolytic benzodiazepine derivative with anticonvulsant, sedative, and amnesic properties. It has also been used in the symptomatic treatment of alcohol withdrawal. Methaminodiazepoxide,7-Chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine-4-oxide,7-Chloro-N-methyl-5-phenyl-3H-1,4-benzodiazepin-2-amine 4-oxide,Chlordiazepoxide Hydrobromide,Chlordiazepoxide Hydrochloride,Chlordiazepoxide Monohydrochloride,Chlordiazepoxide Perchlorate,Chlozepid,Elenium,Librium,7 Chloro 2 methylamino 5 phenyl 3H 1,4 benzodiazepine 4 oxide,7 Chloro N methyl 5 phenyl 3H 1,4 benzodiazepin 2 amine 4 oxide,Hydrobromide, Chlordiazepoxide,Hydrochloride, Chlordiazepoxide,Monohydrochloride, Chlordiazepoxide,Perchlorate, Chlordiazepoxide
D002719 Chlormethiazole A sedative and anticonvulsant often used in the treatment of alcohol withdrawal. Chlormethiazole has also been proposed as a neuroprotective agent. The mechanism of its therapeutic activity is not entirely clear, but it does potentiate GAMMA-AMINOBUTYRIC ACID receptors response and it may also affect glycine receptors. Clomethiazole,Distraneurin
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
D005849 Gerbillinae A subfamily of the Muridae consisting of several genera including Gerbillus, Rhombomys, Tatera, Meriones, and Psammomys. Gerbils,Jird,Meriones,Psammomys,Rats, Sand,Gerbil,Jirds,Merione,Rat, Sand,Sand Rat,Sand Rats
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
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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