Perinatal cocaine exposure impairs myocardial beta-adrenoceptor signaling in the neonatal rat.
Cardiac dysfunction occurs in infants with prenatal cocaine exposure, and gestational cocaine exposure induces presynaptic and postsynaptic changes in the central monoaminergic receptor pathways. The hypothesis of this study is that prenatal cocaine exposure adversely affects the peripheral adrenergic receptor (betaAR) signaling pathway in the neonatal rat heart. Timed pregnant rats received daily intragastric treatment with saline or cocaine 20 mg/kg or 60 mg/kg from Gestational Day 2 until parturition. After birth, nursing mothers either continued to receive the same treatment or received no treatment. Adenylyl cyclase activity, betaAR density, and the amount of immunoreactive G proteins were measured in myocardial membranes obtained from the offspring on Postnatal Day 1 or 7. On Postnatal Day 1, prenatal cocaine exposure increased the betaAR number but did not affect isoproterenol-stimulated adenylyl cyclase activity. On Postnatal Day 7, perinatal cocaine exposure significantly attenuated isoproterenol-stimulated adenylyl cyclase activity in the absence of betaAR up-regulation. Prenatal cocaine exposure also significantly increased Gi protein and reduced GTP-stimulated adenylyl cyclase activity in Postnatal Day 1 cocaine (20 mg/kg) pups compared with saline (P < 0.05). Therefore, perinatal cocaine exposure impaired the myocardial betaAR-cAMP signaling pathway during the first week of postnatal life in the rat.


CONCLUSIONS
This study shows that maternal cocaine use during pregnancy impairs the beta-adrenoceptor signaling pathway in the rat during the first week of life. Abnormal cardiac function in the cocaine-exposed neonate may be related to a defect in beta-adrenoceptors, because they regulate cardiac function.
Sun
L S
LS
Department of Anesthesiology and Pediatrics, College of Physicians and Surgeons, Columbia University, New York, New York, USA. LSS4@columbia.edu
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D003042:Cocaine / Q000633:toxicity*; D000242:Cyclic AMP / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity*; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D015151:Immunoblotting; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*
D018765:Dopamine Uptake Inhibitors; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D003042:Cocaine