Anxiolytic drugs and the acquisition of conditioned fear in mice. 1985

D J Sanger, and D Joly

Previous studies have shown that, in rodents, chlordiazepoxide and other benzodiazepines can interfere with learning in passive avoidance or conditioned suppression procedures. The most consistent effects are observed when the drugs are administered before the acquisition trial and subjects are re-tested in the non-drugged state. It is not clear, however, whether this effect on learning is associated with the behavioural depressant actions of these drugs. In the present study mice were injected with chloridiazepoxide, diazepam, zopiclone, or CGS 9896 and locomotor activity measured in a two-compartment box. The animals were then enclosed in one of the compartments and received a series of footshocks. On a second trial, 24 h after the first, the mice were returned to the box without injection and locomotion and time spent in each compartment were measured. During trial 1 chlordiazepoxide, diazepam, and zopiclone produced dose-related decreases in locomotor activity. The same doses disrupted fear conditioning. CGS 9896 also interfered with the conditioning of fear but did not reduce exploratory activity during the first trial at any of a wide range of doses, showing that learning can be affected without direct behavioural depressant activity. In a further experiment, chlordiazepoxide and CGS 9896 disrupted fear conditioning when injected before trial 1 but not when injected immediately after this trial. Mice drugged with chlordiazepoxide or CGS 9896 before both trials 1 and 2 also showed disrupted conditioning, demonstrating that the drug effects cannot be interpreted in terms of state dependent learning.

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
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D011720 Pyrazoles Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
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
D003213 Conditioning, Psychological Simple form of learning involving the formation, strengthening, or weakening of an association between a stimulus and a response. Conditioning, Psychology,Psychological Conditioning,Social Learning Theory,Social Learning Theories,Theory, Social Learning
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
D005239 Fear The affective response to an actual current external danger which subsides with the elimination of the threatening condition. Threat Cues,Threat Sensitivity,Cue, Threat,Fears,Sensitivity, Threat,Threat Cue,Threat Sensitivities
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
D014151 Anti-Anxiety Agents Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here. Anti-Anxiety Agent,Anti-Anxiety Drug,Anxiolytic,Anxiolytic Agent,Anxiolytic Agents,Tranquilizing Agents, Minor,Anti-Anxiety Drugs,Anti-Anxiety Effect,Anti-Anxiety Effects,Antianxiety Effect,Antianxiety Effects,Anxiolytic Effect,Anxiolytic Effects,Anxiolytics,Tranquillizing Agents, Minor,Agent, Anti-Anxiety,Agent, Anxiolytic,Agents, Anti-Anxiety,Agents, Anxiolytic,Agents, Minor Tranquilizing,Agents, Minor Tranquillizing,Anti Anxiety Agent,Anti Anxiety Agents,Anti Anxiety Drug,Anti Anxiety Drugs,Anti Anxiety Effect,Anti Anxiety Effects,Drug, Anti-Anxiety,Drugs, Anti-Anxiety,Effect, Anti-Anxiety,Effect, Antianxiety,Effect, Anxiolytic,Effects, Anti-Anxiety,Effects, Antianxiety,Effects, Anxiolytic,Minor Tranquilizing Agents,Minor Tranquillizing Agents

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