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

100 Citations (Scopus)

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
Externally publishedYes

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Brain-Derived Neurotrophic Factor
Morphine
Ventral Tegmental Area
Reward
Dopaminergic Neurons
Nucleus Accumbens
Neuronal Plasticity
Aptitude
Street Drugs
Cocaine
Dopamine
Brain
Genes

ASJC Scopus subject areas

  • General

Cite this

Koo, J. W., Mazei-Robison, M. S., Chaudhury, D., Juarez, B., LaPlant, Q., Ferguson, D., ... Nestler, E. J. (2012). BDNF is a negative modulator of morphine action. Science, 338(6103), 124-128. https://doi.org/10.1126/science.1222265

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

In: Science, Vol. 338, No. 6103, 05.10.2012, p. 124-128.

Research output: Contribution to journalArticle

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
Koo JW, Mazei-Robison MS, Chaudhury D, Juarez B, LaPlant Q, Ferguson D et al. BDNF is a negative modulator of morphine action. Science. 2012 Oct 5;338(6103):124-128. https://doi.org/10.1126/science.1222265
Koo, Ja Wook ; Mazei-Robison, Michelle S. ; Chaudhury, Dipesh ; Juarez, Barbara ; LaPlant, Quincey ; Ferguson, Deveroux ; Feng, Jian ; Sun, Haosheng ; Scobie, Kimberly N. ; Damez-Werno, Diane ; Crumiller, Marshall ; Ohnishi, Yoshinori N. ; Ohnishi, Yoko H. ; Mouzon, Ezekiell ; Dietz, David M. ; Lobo, Mary Kay ; Neve, Rachael L. ; Russo, Scott J. ; Han, Ming Hu ; Nestler, Eric J. / BDNF is a negative modulator of morphine action. In: Science. 2012 ; Vol. 338, No. 6103. pp. 124-128.
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