Tolerance and cross-tolerance to central nervous system depressants after chronic pentobarbital or chronic methaqualone administration.
This study reports on tolerance and cross-tolerance to the rotarod (RR)-disrupting effects of various central nervous system (CNS) depressants. Female rats trained on the RR were fed ground chow containing pentobarbital (PB, 2.0 mg/g chow) or methaqualone (MQ, 1.0 mg/g chow) and were injected twice daily (PB) or daily MQ) with 30 mg/kg IP for 6 days. Control rats received ground chow and saline injections. On day 7 the subjects were tested with various doses of PB, MQ, diazepam (DZ), or ethanol (ET) for disruption of RR performance over the time-course of the drug effect (up to 12 hours). Control animals demonstrated a dose-dependent duration of impairment for all 4 agents. Both groups receiving chronic drug showed a prominent decrease in duration of RR impairment after PB, a less marked decrease after MQ, and even less of a decrease after DZ. However, neither chronic drug group showed an appreciable tolerance to the RR disruption of ET, relative to the control group. Based on the time of 50% recovery (RR performance recovering to 90 seconds or more), both chronic treatments resulted in a significant shift of the dose-response curves for PB, MQ and DZ to the right. Therefore, the degree of tolerance and cross-tolerance in rats chronically treated with PB or MQ was dramatic for PB and MQ, was significant for DZ, but was not demonstrable for ET.
D000818:Animals; D003864:Depression, Chemical; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008702:Methaqualone / Q000494:pharmacology*; D009048:Motor Skills / Q000187:drug effects*; D010424:Pentobarbital / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000431:Ethanol; D008702:Methaqualone; D010424:Pentobarbital; D003975:Diazepam