Neurotrophin-4 is required for tolerance to morphine in the mouse.

Tolerance is an important component of opiate addiction, but the molecular basis for this phenomenon remains obscure. Here, we report that mice lacking neurotrophin-4 (NT4) display substantially reduced tolerance to morphine compared to wild-type. However, there were no deficits in sensitization and withdrawal, other behaviors relevant to drug addiction. Since NT4 knockout mice also show abnormalities in long-term but not short-term memory, our findings suggest common molecular pathways for some of the enduring changes of drug addiction and memory consolidation.