Blockade of D1 dopaminergic transmission alleviates c-fos induction and cleaved caspase-3 expression in the brains of rat pups exposed to prenatal cocaine or perinatal asphyxia.
Hypoxia due to uterine vasoconstriction may be an important cause of the teratogenic consequences of prenatal cocaine exposure. We used immediate-early gene and cleaved caspase-3 expression patterns to monitor fetal brain regions affected by intrauterine hypoxia and prenatal cocaine and pretreatment with the D1 dopamine receptor antagonist SCH 23390 to determine how much of the induction observed was due to dopamine. Both cocaine binge (3 x 15 mg/kg) and perinatal asphyxia on embryonic day 22 (E22) induced c-fos in the striatum as well as in several other brain regions within 3 h after treatment. Maternal administration of a D1 dopamine antagonist, SCH 23390, before either cocaine or asphyxia exposure dramatically reduced the numbers of Fos-immunoreactive cells in the striatum as well as in many other brain regions. Cells immunoreactive for cleaved caspase-3 expression were more numerous after perinatal asphyxia than after prenatal cocaine exposure in most brain regions 24 h after C-section. SCH 23390 decreased caspase-3 expression after both birth insults, indicating that the increased incidence of apoptosis is related to overactivation of dopaminergic pathways.
Mitchell
Ellen S
ES
Department of Biomedical Sciences, State University at Albany, Albany, NY, USA. mitchell@wadsworth.org
Snyder-Keller
Abigail
A
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001237:Asphyxia / Q000378:metabolism*; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D009435:Synaptic Transmission / Q000187:drug effects
D001552:Benzazepines; D018492:Dopamine Antagonists; D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D003042:Cocaine