Involvement of the bed nucleus of the stria terminalis in L-Dopa induced dyskinesia

Sci Rep. 2017 May 24;7(1):2348. doi: 10.1038/s41598-017-02572-9.


A whole brain immediate early gene mapping highlighted the dorsolateral bed nucleus of the stria terminalis (dlBST) as a structure putatively involved in L-3,4-dihydroxyphenylalanine (L-Dopa)-induced dyskinesia (LID), the debilitating side-effects of chronic dopamine replacement therapy in Parkinson's disease (PD). dlBST indeed displayed an overexpression of ∆FosB, ARC, Zif268 and FRA2 only in dyskinetic rats. We thus hypothesized that dlBST could play a role in LID hyperkinetic manifestations. To assess the causal role of the dlBST in LID, we used Daun02 inactivation to selectively inhibit the electrical activity of dlBST ΔFosB-expressing neurons. Daun02 is a prodrug converted into Daunorubicin by ß-galactosidase. Then, the newly synthesized Daunorubicin is an inhibitor of neuronal excitability. Therefore, following induction of abnormal involuntary movements (AIMs), 6-OHDA rats were injected with Daun02 in the dlBST previously expressing ß-galactosidase under control of the FosB/ΔFosB promoter. Three days after Daun02 administration, the rats were tested daily with L-Dopa to assess LID. Pharmacogenetic inactivation of ∆FosB-expressing neuron electrophysiological activity significantly reduced AIM severity. The present study highlights the role of dlBST in the rodent analog of LID, offering a new target to investigate LID pathophysiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparkinson Agents / therapeutic use
  • Antiparkinson Agents / toxicity
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Daunorubicin / analogs & derivatives
  • Daunorubicin / pharmacology
  • Disease Models, Animal
  • Dyskinesia, Drug-Induced / etiology
  • Dyskinesia, Drug-Induced / genetics*
  • Dyskinesia, Drug-Induced / prevention & control
  • Gene Expression / drug effects
  • Levodopa / pharmacology
  • Levodopa / toxicity*
  • Male
  • Neurons / drug effects
  • Neurons / metabolism
  • Parkinson Disease / drug therapy
  • Proto-Oncogene Proteins c-fos / genetics
  • Rats, Sprague-Dawley
  • Septal Nuclei / metabolism*


  • Antiparkinson Agents
  • Fosb protein, rat
  • N-(4''-(galactopyranosyl)-3''-nitrobenzyloxycarbonyl)daunomycin
  • Proto-Oncogene Proteins c-fos
  • Levodopa
  • Daunorubicin