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.
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Ja Wook
authors.initials: JW
authors.lastname: Koo
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Mazei-Robison
authors.forename: Dipesh
authors.initials: D
authors.lastname: Chaudhury
authors.forename: Barbara
authors.initials: B
authors.lastname: Juarez
authors.forename: Quincey
authors.initials: Q
authors.lastname: LaPlant
authors.forename: Deveroux
authors.initials: D
authors.lastname: Ferguson
authors.forename: Jian
authors.initials: J
authors.lastname: Feng
authors.forename: Haosheng
authors.initials: H
authors.lastname: Sun
authors.forename: Kimberly N
authors.initials: KN
authors.lastname: Scobie
authors.forename: Diane
authors.initials: D
authors.lastname: Damez-Werno
authors.forename: Marshall
authors.initials: M
authors.lastname: Crumiller
authors.forename: Yoshinori N
authors.initials: YN
authors.lastname: Ohnishi
authors.forename: Yoko H
authors.initials: YH
authors.lastname: Ohnishi
authors.forename: Ezekiell
authors.initials: E
authors.lastname: Mouzon
authors.forename: David M
authors.initials: DM
authors.lastname: Dietz
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Lobo
authors.forename: Rachael L
authors.initials: RL
authors.lastname: Neve
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Russo
authors.forename: Ming-Hu
authors.initials: MH
authors.lastname: Han
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D055786:Gene Knockout Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000235:genetics / Q000503:physiopathology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D010775:Photic Stimulation; D020813:Receptor, trkB / Q000235:genetics / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009020:Morphine; D020813:Receptor, trkB; D004298:Dopamine