Cellular and metabolic tolerance to an opioid narcotic in mouse brain

Abstract

1 Running activity and brain levorphanol concentration were measured in nontolerant and tolerant mice given various doses of ³H-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.