Cellular and learned tolerances to chlordiazepoxide hypothermia and ataxia.
Four groups of rats received chlordiazepoxide (CDP): a) intermittently, experiencing hypothermia and rotarod performance (RR) deficit after test doses (contingency); b) chronically, experiencing hypothermia and RR deficit after test doses; c) intermittently, RR preceding test doses and with protection against hypothermia afforded by exposure to heat lamps (nonexperienced, noncontingency); and d) chronically, RR preceding test doses and with protection against hypothermia. After 36 days of chronic CDP (groups 2 and 4) or vehicle (groups 1 and 3), all groups experienced RR and body temperature (BT) drug deficits after test doses of CDP at the postwithdrawal test. Group 1 but not group 3 was tolerant to peak hypothermia of the drug. Both chronic groups (2 and 4) showed marked tolerance to hypothermia. At the postwithdrawal test, after discontinuing chronic CDP or vehicle for 9 days, only groups 2 and 4 lost drug tolerance to hypothermia. After extinction training (daily testing of RR and BT after injecting vehicle over 9 days), group 2 but not group 4 was again less sensitive to CDP-induced hypothermia at the postextinction test. Regarding CDP-induced RR ataxia, group 1 was more tolerant than group 3 at the postchronic test, while group 4 but not group 2 also showed tolerance to ataxia. At the postwithdrawal test, only group 4 lost tolerance to peak RR ataxic effects of CDP. At the postextinction test, only group 1 lost tolerance for ataxia relative to postchronic test results.(ABSTRACT TRUNCATED AT 250 WORDS)
MacKenzie-Taylor
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Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Rech
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D000818:Animals; D001259:Ataxia / Q000139:chemically induced*; D001831:Body Temperature / Q000187:drug effects; D002707:Chlordiazepoxide / Q000494:pharmacology*; D004361:Drug Tolerance; D007035:Hypothermia / Q000139:chemically induced*; D007858:Learning / Q000187:drug effects*; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D002707:Chlordiazepoxide; D010424:Pentobarbital