Cellular and metabolic tolerance to an opioid narcotic in mouse brain.
1. Running activity and brain levorphanol concentration were measured in nontolerant and tolerant mice given various doses of (3)H-levorphanol.2. The principal factor responsible for tolerance in the mouse is a loss of sensitivity to the narcotic drug at the cellular level in brain; despite adequate brain concentrations, the pharmacological effects are diminished or absent.3. There is also metabolic tolerance; a given dose establishes a lower brain concentration in tolerant than in non-tolerant animals.4. The two kinds of tolerance are distinguished here and the contribution of each is assessed.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D002855:Chromatography, Thin Layer; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D007274:Injections, Intraperitoneal; D007981:Levorphanol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D013997:Time Factors; D014316:Tritium
D014316:Tritium; D007981:Levorphanol