Perinatal cocaine exposure impairs myocardial beta-adrenoceptor signaling in the neonatal rat

Cardiac dysfunction occurs in infants with prenatal cocaine exposure, and g estational 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 adrenerg ic receptor (PAR) signaling pathway in the neonatal rat heart. Timed pregna nt rats received daily intragastric treatment with saline or cocaine 20 mg/ kg or 60 mg/kg from Gestational Day 2 until parturition. After birth, nursi ng mothers either continued to receive the same treatment or received no tr eatment. Adenylyl cyclase activity, PAR density, and the amount of immunore active G proteins were measured in myocardial membranes obtained from the o ffspring on Postnatal Day 1 or 7. On Postnatal Day 1, prenatal cocaine expo sure increased the PAR number but did not affect isoproterenol-stimulated a denylyl cyclase activity. On Postnatal Day 7, perinatal cocaine exposure si gnificantly attenuated isoproterenol-stimulated adenylyl cyclase activity i n the absence of PAR up-regulation. Prenatal cocaine exposure also signific antly increased Gi protein and reduced Gm-stimulated adenylyl cyclase activ ity in Postnatal Day 1 cocaine (20 mg/kg) pups compared with saline (P < 0. 05). Therefore, perinatal cocaine exposure impaired the myocardial beta AR- cAMP signaling pathway during the first week of postnatal life in the rat. Implications: This study shows that maternal cocaine use during pregnancy i mpairs 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.