Implication of brain-derived neurotrophic factor in the release of dopamine and dopamine-related behaviors induced by methamphetamine

Neuroscience. 2003;119(3):767-75. doi: 10.1016/s0306-4522(03)00099-x.


It is widely recognized that methamphetamine enhances the release of dopamine at dopaminergic neuron terminals of the mesolimbic system, which induces dopamine-related behaviors. Brain-derived neurotrophic factor (BDNF), a neurotrophin, binds to and activates its specific receptor tyrosine kinase, TrkB. BDNF has been shown to influence the release of dopamine in the mesolimbic dopamine system. The present study was designed to investigate roles of BDNF and TrkB in the expression of methamphetamine-induced dopamine release in the nucleus accumbens and dopamine-related behaviors induced by methamphetamine in rats. Methamphetamine (1 mg/kg, s.c.) produced a substantial increase in the extracellular levels of dopamine and induced a progressive augmentation of dopamine-related behaviors such as rearing and sniffing. In contrast, both the stimulation of dopamine release and induction of dopamine-related behaviors by methamphetamine were significantly suppressed by pretreatment with intra-nucleus accumbens injection of either BDNF (2.0 microl/rat, 1:1000, 1:300 and 1:100) or TrkB (2.0 microl/rat, 1:1000 and 1:100) antibody. Furthermore, the basal level of dopamine in the nucleus accumbens was not affected by treatment with both BDNF and TrkB antibodies. These findings provide further evidence that BDNF/TrkB pathway is implicated in the methamphetamine-induced release of dopamine and the induction of dopamine-related behaviors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine-Related Disorders / metabolism*
  • Amphetamine-Related Disorders / physiopathology
  • Animals
  • Antibodies / pharmacology
  • Brain-Derived Neurotrophic Factor / antagonists & inhibitors
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • Male
  • Methamphetamine / pharmacology*
  • Neural Pathways / drug effects*
  • Neural Pathways / metabolism
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Receptor, trkB / antagonists & inhibitors
  • Receptor, trkB / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Up-Regulation / drug effects
  • Up-Regulation / physiology


  • Antibodies
  • Brain-Derived Neurotrophic Factor
  • Methamphetamine
  • Receptor, trkB
  • Dopamine