Evidence for limited D1 and D2 receptor coexpression and colocalization within the dorsal striatum of the neonatal mouse

J Comp Neurol. 2015 Jun 1;523(8):1175-89. doi: 10.1002/cne.23730. Epub 2015 Feb 17.


The striatum is the major input nucleus of the basal ganglia involved in reward processing, goal-directed behaviors, habit learning, and motor control. The striatum projects to the basal ganglia output nuclei via the "direct" and "indirect" pathways, which can be distinguished by their projection fields and their opposing effects on behavior. In adult animals, the functional opposition is modulated by the differential actions of D1 and D2 dopamine receptors (D1R, D2R), the expression of which is largely separated between these pathways. To determine whether a similar degree of separation exists earlier in development, we used dual-label immunohistochemistry to map dorsal-striatal D1R and D2R expression at the promoter level in postnatal day 0 (PD0) Drd1a-tdTomato/Drd2-GFP BAC transgenic mice, and at the receptor level by costaining for native D1R and D2R in wildtype (WT) PD0 animals. To assess for potential molecular interactions between D1R and D2R we also employed a recently developed proximity-ligation assay (PLA). Limited coexpression and colocalization of the D1R and D2R proteins was found in clusters of neurons endemic to the "patch" compartment as identified by costaining with tyrosine hydroxylase, but not outside these clusters. Moreover, in contrast to our recent findings where we failed to detect a D1R-D2R PLA signal in the adult striatum, in PD0 striatum we did identify a clear PLA signal for this pair of receptors. This colocalization at close proximity points to a possible role for D1R/D2R-mediated crosstalk in early striatal ontogeny.

Keywords: AB_10013483; AB_10710873; AB_1840787; AB_2079751; AB_300798; IMSR_JAX:016204; IMSR_MMRRC:000230; RRID: AB_11213750; dopamine receptors; matrix; neonate; nif-0000-30467; nlx_153890; patch; proximity-ligation assay; rid_000081; striatum.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Corpus Striatum / growth & development*
  • Corpus Striatum / metabolism*
  • Fluorescent Antibody Technique
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Confocal
  • Neurons / metabolism*
  • Receptors, Dopamine D1 / genetics
  • Receptors, Dopamine D1 / metabolism*
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism*
  • Tyrosine 3-Monooxygenase / metabolism


  • DRD2 protein, mouse
  • Drd1 protein, mouse
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Green Fluorescent Proteins
  • Tyrosine 3-Monooxygenase