Cellular and learned tolerances for pentobarbital hypothermia.
The development of behavioral tolerance to pentobarbital-induced hypothermia, as separable from cellular and metabolic tolerance, was established. Pentobarbital (PB) was administered to 4 groups of rats, 2 groups of which received intermittent (INT) IP PB treatment. One of these groups, INT/EXP, experienced the hypothermic (measured as rectal body temperature) drug effect after PB injection. The other group, INT/NONEXP, was monitored for body temperature functions (room temperature) before receiving PB (vehicle administration) and then prevented from experiencing PB-induced hypothermia by maintenance of body temperature with a towel wrap restraint and a heating lamp. The INT/EXP group also received equivalent exposure to this towel wrap after vehicle administration. Two other groups received chronic PB treatment (IP and in ground chow), one with experience for hypothermia after injections (CHR/EXP) and one prevented from experiencing the hypothermia (CHR/NONEXP). These groups also received equivalent exposure to the body temperature (at room temperature) testing and towel wrap restraint, EXP rats after vehicle injections and NONEXP after drug injections. A postchronic test of all groups compared the extent of PB hypothermia to prechronic test effects to assess the degree of tolerance. The INT/EXP group demonstrated behavioral tolerance for PB-induced hypothermia, as contrasted with the INT/NONEXP group which demonstrated little or no tolerance. Prominent tolerance was noted in both chronic groups for PB hypothermia, without a significant difference between them. After the postchronic test, chronic treatment was discontinued for 9 days (withdrawal) followed by 9 days of extinction training (vehicle behavioral testing). The two intermittent groups demonstrated no change in the hypothermic drug response during the postwithdrawal and postextinction drug tests.(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; D001921:Brain / Q000378:metabolism; D004361:Drug Tolerance; D007035:Hypothermia / Q000139:chemically induced* / Q000503:physiopathology; D007858:Learning / Q000187:drug effects*; D008297:Male; D010424:Pentobarbital / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D010424:Pentobarbital