Effects of two acute stressors on the anxiolytic efficacy of chlordiazepoxide.
BACKGROUND
Limited published data show that drug efficacy can be influenced by stressors. Thus, drug testing in stressed animals may unravel important variables determining drug effects.


OBJECTIVE
The experiments tested the anxiolytic efficacy of the benzodiazepine chlordiazepoxide under conditions of acute stress.


METHODS
Previously group-housed rats were injected with 0, 3, and 10 mg/kg chlordiazepoxide, thereafter being exposed to two types of stress: novelty (transfer to an individual cage) and social defeat. Controls were group-housed animals. Anxiety was assessed on the plus maze.


RESULTS
Speed of locomotion was increased by chlordiazepoxide in both stressed groups but not in controls. Chlordiazepoxide exerted a marked reduction in anxiety in controls and defeated rats but not in novelty exposed animals. The effects of novelty exposure were considerably weaker when drug testing was performed 24 h later.


CONCLUSIONS
Stress exposure had an impact on the behavioral effects of chlordiazepoxide. Changes in locomotor activity induced by the drug appear to depend on the presence of a stressor, while anxiolytic efficacy appears to depend on the type of the stressor. Since it has been shown that drug efficacy changes in a variety of behavioral situations and drug classes, it is suggested that experimental background is an important variable in determining behavioral effects of drugs.
Haller
J
J
Institute of Experimental Medicine, Hungarian Academy of Science, Budapest, Hungary. haller@koki.hu
Halász
J
J
D000208:Acute Disease; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000150:complications / Q000188:drug therapy*; D002707:Chlordiazepoxide / Q000627:therapeutic use*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000150:complications* / Q000188:drug therapy
D014151:Anti-Anxiety Agents; D002707:Chlordiazepoxide