Addicts report that opiate drugs lose their rewarding effects over time, but the molecular mechanisms underlying this effect are unknown. A study now reports that tolerance to morphine reward in rats is due to downregulation of IRS2-Akt signaling in the ventral tegmental area (VTA), the cell body region of the mesolimbic dopamine reward system.
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Harvey, B., Hope, B. & Shaham, Y. Tolerance to opiate reward: role of midbrain IRS2-Akt pathway. Nat Neurosci 10, 9–10 (2007). https://doi.org/10.1038/nn0107-9
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DOI: https://doi.org/10.1038/nn0107-9
