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Updated: Aug 11, 2026

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Neurotrophin-4 is required for tolerance to morphine in the mouse
Desmond J Smith1, Tarek A Leil, Xin Liu
1Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA 90095, USA.
Abstract:
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.
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