Dcc haploinsufficiency regulates dopamine receptor expression across postnatal lifespan

Area of Science:

• Neuroscience
• Developmental Neuroscience
• Molecular Neuroscience

Background:

• Adolescence involves significant medial prefrontal cortex (mPFC) remodeling.
• Deleted in colorectal cancer (DCC) receptor signaling regulates mPFC dopamine connectivity and maturation.
• DCC haploinsufficiency enhances cognitive processing and resilience to stimulant drugs.

Purpose of the Study:

• To investigate the impact of DCC haploinsufficiency on dopamine receptor expression dynamics in the mouse forebrain during adolescence.
• To characterize age- and region-specific alterations in D1 and D2 receptor density in Dcc haploinsufficient versus wild-type mice.

Main Methods:

• Quantitative receptor autoradiography using [3H]SCH-23390 (D1) and [3H]raclopride (D2) ligands.
• Analysis of dopamine receptor expression in mPFC and striatal regions of male C57BL6 mice at PND21, PND35, and PND75.
• Comparison of Dcc haploinsufficient mice with wild-type littermates.

Main Results:

• C57BL6 mice show D1 receptor overexpression and pruning in striatum, but not mPFC, during adolescence.
• Dcc haploinsufficiency results in age- and region-specific differences in D1 and D2 receptor densities.
• Neither wild-type nor haploinsufficient mice exhibit typical mPFC dopamine receptor pruning; adult haploinsufficient mice display increased mPFC D2 receptor density.

Conclusions:

• DCC receptors are crucial for the dynamic refinement of dopamine receptor expression in striatal regions during adolescence.
• Adolescent dopamine receptor expression patterns in C57BL6 mice differ from those previously reported in rats.
• DCC signaling influences the developmental trajectory of dopamine receptor systems in the adolescent brain.