title: Dopamine D1 receptor changes due to caesarean section birth: effects of anesthesia, developmental time course, and functional consequences.
abstract: There is an epidemiological association between increased obstetric complications and disorders involving CNS dopamine dysregulation, such as schizophrenia. In light of this, a rat model of global hypoxia during Caesarean section (C-section) birth has been used to directly test if birth complications can produce long-term dopaminergic dysregulation. Previous studies have shown that, compared to vaginal birth, C-section birth alone (without additional global hypoxia) is sufficient to increase D1-like receptor binding in rat brain at adulthood. The current study examined (1) the developmental time course of changes in D1-like or D2-like receptors following C-section birth; (2) whether C-section birth from isoflurane-anesthetized dams also results in altered D1-like receptor levels, as does C-section from decapitated dams; and (3) behavioral responses to D1 and D2 agonists in rats born vaginally compared to C-section. Increases in nucleus accumbens D1-like receptor binding due to C-section birth were observed only at adulthood (3 months) but not prepubertally (1 month or 2 weeks). D2-like receptor binding levels were unaffected by C-section birth across the three developmental time points. Compared to vaginal birth, D1-like receptors were increased following C-section birth from isoflurane-anesthetized dams, as well as from decapitated dams. Adult rats that had been born by C-section showed enhanced D1 potentiation of D2-induced locomotor behavior. These studies indicate that C-section birth, from either anesthetized or unanesthetized dams, results in postpubertal increases in D1-like receptor binding and enhanced functional responses to D1 receptor activation.
authors.affiliation: Department of Psychiatry, McGill University, Douglas Hospital Research Centre, 6875 LaSalle Boulevard, Verdun, Quebec H4H 1R3, Canada. patricia.boksa@mcgill.ca
authors.forename: Patricia
authors.initials: P
authors.lastname: Boksa
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Alain
authors.initials: A
authors.lastname: Bestawros
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D002585:Cesarean Section; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D007530:Isoflurane / Q000494:pharmacology*; D007743:Labor, Obstetric / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism
chemical_list: D000662:Amphetamines; D018685:Anesthetics, Inhalation; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D007530:Isoflurane