Amphetamine-induced locomotion and gene expression are altered in BDNF heterozygous mice

Genes Brain Behav. 2008 Nov;7(8):906-14. doi: 10.1111/j.1601-183X.2008.00430.x. Epub 2008 Aug 4.


Administration of amphetamine overstimulates medium spiny neurons (MSNs) by releasing dopamine and glutamate from afferents in the striatum. However, these afferents also release brain-derived neurotrophic factor (BDNF) that protects striatal MSNs from overstimulation. Intriguingly, all three neurochemicals increase opioid gene expression in MSNs. In contrast, striatal opioid expression is less in naive BDNF heterozygous (BDNF(+/-)) vs. wild-type (WT) mice. This study was designed to determine whether partial genetic depletion of BDNF influences the behavioral and molecular response to an acute amphetamine injection. An acute injection of amphetamine [5 mg/kg, intraperitoneal (i.p.)] or saline was administered to WT and BDNF(+/-) mice. WT and BDNF(+/-) mice exhibited similar locomotor activity during habituation, whereas BDNF(+/-) mice exhibited more prolonged locomotor activation during the third hour after injection of amphetamine. Three hours after amphetamine injection, there was an increase of preprodynorphin mRNA in the caudate putamen and nucleus accumbens (Acb) and dopamine D(3) receptor mRNA levels were increased in the Acb of BDNF(+/-) and WT mice. Striatal/cortical trkB and BDNF, and mesencephalic tyrosine hydroxylase mRNA levels were only increased in WT mice. These results indicate that BDNF modifies the locomotor responses of mice to acute amphetamine and differentially regulates amphetamine-induced gene expression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology
  • Amphetamine / pharmacology*
  • Amphetamine-Related Disorders / genetics*
  • Amphetamine-Related Disorders / metabolism
  • Amphetamine-Related Disorders / physiopathology
  • Animals
  • Brain Chemistry / drug effects
  • Brain Chemistry / genetics*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Disease Models, Animal
  • Down-Regulation / genetics
  • Dynorphins / genetics
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / genetics
  • Habituation, Psychophysiologic / drug effects
  • Habituation, Psychophysiologic / genetics
  • Heterozygote
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / drug effects*
  • Motor Activity / genetics
  • Neostriatum / drug effects
  • Neostriatum / metabolism
  • Neostriatum / physiopathology
  • Neurons / drug effects
  • Neurons / metabolism
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Nucleus Accumbens / physiopathology
  • Protein Precursors / genetics
  • Receptor, trkB / genetics
  • Receptors, Dopamine D3 / genetics
  • Time Factors


  • Adrenergic Uptake Inhibitors
  • Brain-Derived Neurotrophic Factor
  • Protein Precursors
  • Receptors, Dopamine D3
  • pre-prodynorphin
  • Dynorphins
  • Amphetamine
  • Receptor, trkB