Strain-specific proportion of the two isoforms of the dopamine D2 receptor in the mouse striatum: Associated neural and behavioral phenotypes

V. Colelli, M. T. Fiorenza, D. Conversi, C. Orsini, S. Cabib

Research output: Contribution to journalArticle

Abstract

Genetic variability in the proportion of the two alternative dopamine D2 receptor (D2R) mRNA splice variants, D2R-long (D2L) and D2R-short (D2S), influence corticostriatal functioning and could be implicated in liability to psychopathology. This study compared mesostriatal D2L/D2S ratios and associated neural and behavioral phenotypes in mice of the DBA/2J and C57BL/6J-inbred strains, which differ for schizophrenia- and addiction-like phenotypes. Results showed that DBA/2J mice lack the striatal predominance of D2L that has been reported in the rat and in C57BL/6J mice and confirmed in the latter strain by this study. Only C57BL/6J mice showed enhanced striatal c-Fos expression under D1R and D2/3R co-stimulation, indicating synergistic interaction between the subtypes of DA receptors. Instead, DBA/2J mice were characterized by opposing effects of D2/3R and D1R stimulation on striatal c-Fos expression, in line with a more pronounced influence of D2S isoform, and did not express stereotyped climbing under D1R and D2/3R co-stimulation, as reported for D2L-/- mice. Finally, strain-specific modulation of c-Fos expression by D1R and D2/3R co-stimulation was selectively observed in striatal compartments receiving inputs from the prefrontal cortex and involved in the control of motivated behaviors. These results show differences in tissue-specific D2R splicing in mice with intact genotypes and support a role for this phenotype in individual variability of corticostriatal functioning and in liability to psychopathology.

Original languageEnglish
Pages (from-to)703-711
Number of pages9
JournalGenes, Brain and Behavior
Volume9
Issue number7
DOIs
Publication statusPublished - Oct 2010

Keywords

  • Accumbens core
  • Addiction
  • Alternative splicing
  • Dopamine
  • Dorsomedial striatum
  • Fos
  • Schizophrenia
  • Stereotypy
  • Striosomes

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Genetics
  • Neurology

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