Differential regulation of the behavioral effects of chlordiazepoxide. 1994

J S Shumsky, and I Lucki
Department of Pharmacology, University of Pennsylvania, Philadelphia 19104-2649.

Chronic administration of the benzodiazepine (BZ) receptor agonist chlordiazepoxide (CDP) produced tolerance to its motor-impairing effects but little or no tolerance to its hypothermic effects or to its amnesic effects in the radial arm maze. Male Sprague-Dawley rats were pretreated for 14 days with CDP (25 mg/kg, b.i.d., IP) or saline, and chronic treatment was maintained throughout the experiments. Tolerance was evaluated by constructing dose-response curves to CDP following chronic administration of either CDP or saline. Tolerance developed to only certain behavioral effects of CDP. Tolerance developed to the motor-impairing effects of CDP as assessed in three different procedures: rotarod, spontaneous locomotor activity, and acquisition of the step-through inhibitory avoidance response. In contrast, tolerance did not develop to the hypothermic effects of CDP. Tolerance to the amnesic effects of CDP was contingent upon the behavioral procedure. For example, tolerance developed to reductions of retention latency in the step-through inhibitory avoidance response, but not to impairment of the acquisition of radial arm maze performance. These results are consistent with the effects of chronic BZ administration in humans and demonstrate a parallel regulation of drug effects, potentially mediated by regional differences in BZ receptor subtype regulation or composition.

UI MeSH Term Description Entries
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D001831 Body Temperature The measure of the level of heat of a human or animal. Organ Temperature,Body Temperatures,Organ Temperatures,Temperature, Body,Temperature, Organ,Temperatures, Body,Temperatures, Organ
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
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
D004361 Drug Tolerance Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL. Drug Tolerances,Tolerance, Drug,Tolerances, Drug
D004856 Postural Balance A POSTURE in which an ideal body mass distribution is achieved. Postural balance provides the body carriage stability and conditions for normal functions in stationary position or in movement, such as sitting, standing, or walking. Postural Control,Posture Balance,Posture Control,Posture Equilibrium,Balance, Postural,Musculoskeletal Equilibrium,Postural Equilibrium,Balance, Posture,Control, Postural,Control, Posture,Equilibrium, Musculoskeletal,Equilibrium, Postural,Equilibrium, Posture,Postural Controls,Posture Balances,Posture Controls,Posture Equilibriums
D005106 Exploratory Behavior The tendency to explore or investigate a novel environment. It is considered a motivation not clearly distinguishable from curiosity. Curiosity,Novelty-Seeking Behavior,Behavior, Exploratory,Behavior, Novelty-Seeking,Behaviors, Exploratory,Behaviors, Novelty-Seeking,Curiosities,Exploratory Behaviors,Novelty Seeking Behavior,Novelty-Seeking Behaviors
D000647 Amnesia Pathologic partial or complete loss of the ability to recall past experiences (AMNESIA, RETROGRADE) or to form new memories (AMNESIA, ANTEROGRADE). This condition may be of organic or psychologic origin. Organic forms of amnesia are usually associated with dysfunction of the DIENCEPHALON or HIPPOCAMPUS. (From Adams et al., Principles of Neurology, 6th ed, pp426-7) Amnesia, Dissociative,Amnesia, Global,Amnesia, Hysterical,Amnesia, Tactile,Amnesia, Temporary,Amnesia-Memory Loss,Amnestic State,Amnesia Memory Loss,Amnesia-Memory Losses,Amnesias,Amnesias, Dissociative,Amnesias, Global,Amnesias, Hysterical,Amnesias, Tactile,Amnesias, Temporary,Amnestic States,Dissociative Amnesia,Dissociative Amnesias,Global Amnesia,Global Amnesias,Hysterical Amnesia,Hysterical Amnesias,State, Amnestic,States, Amnestic,Tactile Amnesia,Tactile Amnesias,Temporary Amnesia,Temporary Amnesias
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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