Nucleus accumbens-derived glial cell line-derived neurotrophic factor is a retrograde enhancer of dopaminergic tone in the mesocorticolimbic system

J Neurosci. 2010 Oct 27;30(43):14502-12. doi: 10.1523/JNEUROSCI.3909-10.2010.

Abstract

Spontaneous firing of ventral tegmental area (VTA) dopamine (DA) neurons provides ambient levels of DA in target areas such as the nucleus accumbens (NAc) and the prefrontal cortex (PFC). Here we report that the glial cell line-derived neurotrophic factor (GDNF), produced in one target region, the NAc, is retrogradely transported by DA neurons to the VTA where the growth factor positively regulates the spontaneous firing activity of both NAc- and PFC-projecting DA neurons in a mechanism that requires the activation of the mitogen-activated protein kinase (MAPK) pathway. We also show that the consequence of GDNF-mediated activation of the MAPK signaling cascade in the VTA is an increase in DA overflow in the NAc. Together, these results demonstrate that NAc-produced GDNF serves as a retrograde enhancer that upregulates the activity of the mesocorticolimbic DA system.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Western
  • Brain Chemistry
  • Cerebral Cortex / physiology*
  • Cloning, Molecular
  • Dopamine / physiology*
  • Electrophysiology
  • Excitatory Postsynaptic Potentials / physiology
  • Glial Cell Line-Derived Neurotrophic Factor / pharmacology*
  • Humans
  • In Situ Nick-End Labeling
  • In Vitro Techniques
  • Limbic System / physiology*
  • Male
  • Microdialysis
  • Mitogen-Activated Protein Kinases / physiology
  • Nucleus Accumbens / metabolism*
  • Nucleus Accumbens / physiology
  • RNA / biosynthesis
  • RNA / genetics
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sympathectomy, Chemical
  • Ventral Tegmental Area / metabolism

Substances

  • Glial Cell Line-Derived Neurotrophic Factor
  • RNA, Messenger
  • RNA
  • Mitogen-Activated Protein Kinases
  • Dopamine