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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References
Wikler, A. Psychiatr. Q. 26, 270–293 (1952).
Jaffe, J.H. Drug addiction and drug abuse. in Goodman & Gilman's the Pharmacological Basis of Therapeutics (ed. Gilman, A.G., Rall, T.W., Nies, A.S. & Taylor, P.) 522–573 (Pergamon Press, New York, 1990).
Bozarth, M.A. & Wise, R.A. J. Am. Med. Assoc. 254, 81–83 (1985).
Ahmed, S.H., Walker, J.R. & Koob, G.F. Neuropsychopharmacology 22, 413–421 (2000).
Shippenberg, T.S., Emmett-Oglesby, M.W., Ayesta, F.J. & Herz, A. Psychopharmacology (Berl.) 96, 110–115 (1988).
Bechara, A. & van der Kooy, D. Behav. Neurosci. 106, 364–373 (1992).
Nestler, E.J. & Aghajanian, G.K. Science 278, 58–63 (1997).
De Vries, T.J. & Shippenberg, T.S. J. Neurosci. 22, 3321–3325 (2002).
Russo, S.J. et al. Nat. Neurosci. 10, 93–99 (2007).
Sklair-Tavron, L. et al. Proc. Natl. Acad. Sci. USA 93, 11202–11207 (1996).
Neve, R.L., Neve, K.A., Nestler, E.J. & Carlezon, W.A., Jr. Biotechniques 39, 381–391 (2005).
Simonato, M., Manservigi, R., Marconi, P. & Glorioso, J. Trends Neurosci. 23, 183–190 (2000).
Martin, T.J., Walker, L.E., Sizemore, G.M., Smith, J.E. & Dworkin, S.I. Drug Alcohol Depend. 41, 93–100 (1996).
Self, D.W. Biol. Psychiatry 57, 1479–1484 (2005).
Lu, L., Grimm, J.W., Shaham, Y. & Hope, B.T. J. Neurochem. 85, 1604–1613 (2003).
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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