BDNF Is a Negative Modulator of Morphine Action

Science. 2012 Oct 5;338(6103):124-8. doi: 10.1126/science.1222265.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / physiology*
  • Dopamine / metabolism
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / physiology
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Gene Knockout Techniques
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Morphine / pharmacology*
  • Morphine Dependence / genetics
  • Morphine Dependence / physiopathology*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiopathology
  • Photic Stimulation
  • Receptor, trkB / genetics
  • Receptor, trkB / physiology
  • Ventral Tegmental Area / drug effects*
  • Ventral Tegmental Area / physiology

Substances

  • Brain-Derived Neurotrophic Factor
  • Morphine
  • Receptor, trkB
  • Dopamine