title: Dcc haploinsufficiency regulates dopamine receptor expression across postnatal lifespan.
abstract: Adolescence is a period during which the medial prefrontal cortex (mPFC) undergoes significant remodeling. The netrin-1 receptor, deleted in colorectal cancer (DCC), controls the extent and organization of mPFC dopamine connectivity during adolescence and in turn directs mPFC functional and structural maturation. Dcc haploinsufficiency leads to increased mPFC dopamine input, which causes improved cognitive processing and resilience to behavioral effects of stimulant drugs of abuse. Here we examine the effects of Dcc haploinsufficiency on the dynamic expression of dopamine receptors in forebrain targets of C57BL6 mice. We conducted quantitative receptor autoradiography experiments with [3H]SCH-23390 or [3H]raclopride to characterize D1 and D2 receptor expression in mPFC and striatal regions in male Dcc haploinsufficient and wild-type mice. We generated autoradiograms at early adolescence (PND21±1), mid-adolescence (PND35±2), and adulthood (PND75±15). C57BL6 mice exhibit overexpression and pruning of D1, but not D2, receptors in striatal regions, and a lack of dopamine receptor pruning in the mPFC. We observed age- and region-specific differences in D1 and D2 receptor density between Dcc haploinsufficient and wild-type mice. Notably, neither group shows the typical pattern of mPFC dopamine receptor pruning in adolescence, but adult haploinsufficient mice show increased D2 receptor density in the mPFC. These results show that DCC receptors contribute to the dynamic refinement of D1 and D2 receptor expression in striatal regions across adolescence. The age-dependent expression of dopamine receptor in C57BL6 mice shows marked differences from previous characterizations in rats.
authors.affiliation: Douglas Mental Health University Institute, 6875 LaSalle Boulevard, Montréal, Québec H4H 1R3, Canada. Electronic address: matthew.pokinko@mail.mcgill.ca.
authors.forename: Matthew
authors.initials: M
authors.lastname: Pokinko
authors.affiliation: Douglas Mental Health University Institute, 6875 LaSalle Boulevard, Montréal, Québec H4H 1R3, Canada. Electronic address: alanna.grant@gmail.com.
authors.forename: Alanna
authors.initials: A
authors.lastname: Grant
authors.affiliation: Douglas Mental Health University Institute, 6875 LaSalle Boulevard, Montréal, Québec H4H 1R3, Canada. Electronic address: florence.shahabi@mail.mcgill.ca.
authors.forename: Florence
authors.initials: F
authors.lastname: Shahabi
authors.affiliation: Douglas Mental Health University Institute, 6875 LaSalle Boulevard, Montréal, Québec H4H 1R3, Canada. Electronic address: Yvan.Dumont@douglas.mcgill.ca.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Dumont
authors.affiliation: Douglas Mental Health University Institute, 6875 LaSalle Boulevard, Montréal, Québec H4H 1R3, Canada. Electronic address: colleen.manitt@gmail.com.
authors.forename: Colleen
authors.initials: C
authors.lastname: Manitt
authors.affiliation: Douglas Mental Health University Institute, 6875 LaSalle Boulevard, Montréal, Québec H4H 1R3, Canada; Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montréal, Québec H3A 1A1, Canada. Electronic address: cecilia.flores@mcgill.ca.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Flores
mesh_terms: D000375:Aging; D000818:Animals; D003342:Corpus Striatum / Q000254:growth & development / Q000378:metabolism*; D000075389:DCC Receptor; D057895:Haploinsufficiency; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009714:Nucleus Accumbens / Q000254:growth & development / Q000378:metabolism; D017397:Prefrontal Cortex / Q000254:growth & development / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000075389:DCC Receptor; C501910:Dcc protein, mouse; D011956:Receptors, Cell Surface; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D025521:Tumor Suppressor Proteins
keywords: DCC; adolescence; guidance cues; netrin-1; prefrontal cortex; receptor pruning