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

doi:10.1126/science.1222265

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

Biology

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Pages (from-to)	124-128
Number of pages	5
Journal	Science
Volume	338
Issue number	6103
DOIs	https://doi.org/10.1126/science.1222265
State	Published - Oct 5 2012

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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

Koo, JW, Mazei-Robison, MS, Chaudhury, D, Juarez, B, LaPlant, Q, Ferguson, D, Feng, J, Sun, H, Scobie, KN, Damez-Werno, D, Crumiller, M, Ohnishi, YN, Ohnishi, YH, Mouzon, E, Dietz, DM, Lobo, MK, Neve, RL, Russo, SJ, Han, MH & Nestler, EJ 2012, 'BDNF is a negative modulator of morphine action', Science, vol. 338, no. 6103, pp. 124-128. https://doi.org/10.1126/science.1222265

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title = "BDNF is a negative modulator of morphine action",

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.",

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

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AU - Ferguson, Deveroux

AU - Feng, Jian

AU - Sun, Haosheng

AU - Scobie, Kimberly N.

AU - Damez-Werno, Diane

AU - Crumiller, Marshall

AU - Ohnishi, Yoshinori N.

AU - Ohnishi, Yoko H.

AU - Mouzon, Ezekiell

AU - Dietz, David M.

AU - Lobo, Mary Kay

AU - Neve, Rachael L.

AU - Russo, Scott J.

AU - Han, Ming Hu

AU - Nestler, Eric J.

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BDNF is a negative modulator of morphine action

Abstract

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