Development and retention of tolerance to the sedative effects of chlordiazepoxide: role of apparatus cues.
Groups of rats were pretreated for 5 days with chlordiazepoxide (5 to 50 mg/kg) or with control water injections. On the sixth day the rats were given a test dose of chlordiazepoxide (10 mg/kg), or water. The rats that had received 5 days of pretreatment with chlordiazepoxide were significantly less sedated by the test dose than were those given chlordiazepoxide for the first time, i.e. they had developed tolerance. There were no significant differences between the two pretreatment groups in the extent of tolerance. A second experiment examined the effects of associating drug injections with apparatus cues. This had no effect on the development of tolerance, but had a significant effect on its retention: rats pretreated and replaced in their home cages showed complete recovery from tolerance after two drug-free days, whereas those placed in the apparatus after each day's injection retained some tolerance even after two drug-free weeks.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001711:Biotransformation; D002707:Chlordiazepoxide / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D003463:Cues / Q000187:drug effects*; D004361:Drug Tolerance; D006993:Hypnotics and Sedatives; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats
D006993:Hypnotics and Sedatives; D002707:Chlordiazepoxide