Neuronal and behavioural abnormalities in striatal function in DARPP-32-mutant mice

Eur J Neurosci. 1999 Mar;11(3):1114-8. doi: 10.1046/j.1460-9568.1999.00570.x.


We investigated the role of the protein phosphatase inhibitor, dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), in the expression of striatal neuropeptides and in biochemical and behavioural responses to repeated cocaine administration, using DARPP-32 knock-out mice. The striatum of DARPP-32-mutant mice showed heightened substance-P-like immunoreactivity, but normal levels of other neuropeptides. Repeated cocaine administration increased levels of DeltaFosB, a Fos family transcription factor, in the striatum of wild-type mice, and this increase was abolished in DARPP-32-mutant mice. Cocaine (20 mg/kg) acutely induced the same level of locomotor activity in the mutant and wild-type mice, but the mutants showed a higher rate of locomotor sensitization to repeated cocaine exposures. These data show that DARPP-32 is involved in regulating substance P expression in the striatonigral pathway, and in biochemical and behavioural plasticity with chronic administration of cocaine.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology*
  • Cocaine / pharmacology
  • Cocaine-Related Disorders / physiopathology
  • Corpus Striatum / physiopathology*
  • Dopamine Uptake Inhibitors / pharmacology
  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • Enzyme Inhibitors / metabolism*
  • Gene Expression / drug effects
  • Locomotion / drug effects
  • Locomotion / physiology
  • Male
  • Mice
  • Mice, Mutant Strains
  • Nerve Tissue Proteins / genetics*
  • Neurons / chemistry
  • Neurons / physiology*
  • Phosphoproteins / genetics
  • Proto-Oncogene Proteins c-fos / analysis


  • Dopamine Uptake Inhibitors
  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • Enzyme Inhibitors
  • Nerve Tissue Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins c-fos
  • Cocaine