Dopamine D1 receptor changes due to caesarean section birth: effects of anesthesia, developmental time course, and functional consequences.
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.
Boksa
Patricia
P
Department of Psychiatry, McGill University, Douglas Hospital Research Centre, 6875 LaSalle Boulevard, Verdun, Quebec H4H 1R3, Canada. patricia.boksa@mcgill.ca
Zhang
Ying
Y
Bestawros
Alain
A
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
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