Tolerance to opioid narcotics, II. Cellular tolerance to levorphanol in mouse brain

Mice were made tolerant to a large dose of levorphanol, a congener of morphine. Then (3)H-levorphanol was given. The concentration of free, unchanged levorphanol in the brain water (ultrafiltrate) was found to be much higher than required to produce pharmacologic effects in nontolerant animals. The result indicates that tolerance arises from a diminished sensitivity to the drug at cellular or subcellular sites of drug action in the brain.