Cellular and learned tolerance to pentobarbital ataxia.
Pentobarbital was administered to 4 groups of rats: 1) intermittently before testing on the rotarod (RR) (experienced, EXP), 2) chronically (CHR) before testing on the RR (EXP), 3) intermittently (INT) after being tested on the RR (NONEXP), and 4) chronically (CHR) after being tested on the RR (NONEXP). On postchronic testing, Group 1 (INT/EXP) failed to show tolerance to the RR decrement, related to prechronic scores, while Group 3 (INT/NONEXP) actually showed an enhanced RR decrement. Group 2 (CHR/EXP) and Group 4 (CHR/NONEXP) both exhibited prominent tolerance to RR impairment at the postchronic test, with a nonsignificant trend for greater tolerance in Group 2. The lack of an expressed behavioral tolerance in INT/EXP rats and the enhanced RR decrement in INT/NONEXP subjects at the postchronic test was attributed to repeated use of a towel wrap restraint during the chronic treatment period. When the prechronic tests for INT/EXP animals were separated into the first 3 and last 3 days, pentobarbital impairment of RR during days 4-6 was significantly less than during days 1-3. This tolerance in INT/EXP rats was lost at the postchronic testing, while INT/NONEXP subjects had by then developed an enhanced RR impairment to pentobarbital. Following postchronic testing, chronic pentobarbital (CHR/EXP and CHR/NONEXP groups) and chronic vehicle (INT/EXP and INT/NONEXP groups) were discontinued for 9 days (withdrawal), after which an intermediate dose of the drug was tested on RR performance. Next, 9 days of extinction training involved vehicle injection daily before testing RR performance, after which the intermediate drug dose was again tested. INT/EXP and INT/NONEXP groups showed no change in RR impairment at the postwithdrawal and postextinction tests. However, in CHR/EXP rats pentobarbital tolerance was partly lost at the postwithdrawal test, with a significantly greater loss at the postextinction test.(ABSTRACT TRUNCATED AT 250 WORDS)
MacKenzie-Taylor
D R
DR
Department of Pharmacology and Toxicology, Michigan State University, E. Lansing 48824.
Rech
R H
RH
D000818:Animals; D001259:Ataxia / Q000139:chemically induced*; D001921:Brain / Q000378:metabolism; D004361:Drug Tolerance; D005108:Extinction, Psychological / Q000187:drug effects; D007858:Learning / Q000187:drug effects*; D008297:Male; D010424:Pentobarbital / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D010424:Pentobarbital