BDNF is a negative modulator of morphine action

Ja Wook Koo, Michelle S. Mazei-Robison, Dipesh Chaudhury, Barbara Juarez, Quincey LaPlant, Deveroux Ferguson, Jian Feng, Haosheng Sun, Kimberly N. Scobie, Diane Damez-Werno, Marshall Crumiller, Yoshinori N. Ohnishi, Yoko H. Ohnishi, Ezekiell Mouzon, David M. Dietz, Mary Kay Lobo, Rachael L. Neve, Scott J. Russo, Ming Hu Han, Eric J. Nestler

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

Brain-derived neurotrophic factor (BDNF) is a key positive regulator of neural plasticity, promoting, for example, the actions of stimulant drugs of abuse such as cocaine. We discovered a surprising opposite role for BDNF in countering responses to chronic morphine exposure. The suppression of BDNF in the ventral tegmental area (VTA) enhanced the ability of morphine to increase dopamine (DA) neuron excitability and promote reward. In contrast, optical stimulation of VTA DA terminals in nucleus accumbens (NAc) completely reversed the suppressive effect of BDNF on morphine reward. Furthermore, we identified numerous genes in the NAc, a major target region of VTA DA neurons, whose regulation by BDNF in the context of chronic morphine exposure mediated this counteractive function. These findings provide insight into the molecular basis of morphine-induced neuroadaptations in the brain's reward circuitry.

Original languageEnglish (US)
Pages (from-to)124-128
Number of pages5
JournalScience
Volume338
Issue number6103
DOIs
StatePublished - Oct 5 2012

ASJC Scopus subject areas

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    Koo, J. W., Mazei-Robison, M. S., Chaudhury, D., Juarez, B., LaPlant, Q., Ferguson, D., Feng, J., Sun, H., Scobie, K. N., Damez-Werno, D., Crumiller, M., Ohnishi, Y. N., Ohnishi, Y. H., Mouzon, E., Dietz, D. M., Lobo, M. K., Neve, R. L., Russo, S. J., Han, M. H., & Nestler, E. J. (2012). BDNF is a negative modulator of morphine action. Science, 338(6103), 124-128. https://doi.org/10.1126/science.1222265