Perinatal Cocaine Exposure Stimulates the Expression and Activation of CREB in the Neonatal Rat Heart

cAMP response binding protein (CREB) is a transcriptional factor known to regulate gene expression. Phosphorylation of CREB at serine 133 is necessary for CREB activation, and quantification of phospho-CREB (p-CREB) expression is an index of CREB activation. Because CREB expression and activation in specific brain regions are modified after chronic cocaine administration, we sought to determine whether chronic perinatal cocaine exposure affects the expression of CREB and p-CREB in the postnatal rat heart. Pregnant rats were treated daily with saline (control) or cocaine at 20 mg/kg (C20) or 60 mg/kg (C60) by intragastric administration throughout gestation. The expression of total CREB and p-CREB was quantified in nuclear extracts isolated from 1- and 7-d-old neonatal rat hearts. Cardiac nuclear p-CREB was increased in the C20 and C60 groups on d 1 and 7 of age compared with their respective age-matched control groups. The increase in p-CREB expression corresponded to an increase in cAMP response element binding activity. We also assayed nuclear protein kinase A activity, which was up-regulated in d 1 animals with prenatal cocaine exposure, but was comparable in all groups at d 7. Our results suggest that perinatal cocaine exposure stimulates CREB activation in the neonatal heart, and it may be mediated by different mechanisms at d 1 and d 7. The changes in myocardial CREB activation induced by perinatal cocaine exposure are likely to result in modified gene expression in the neonatal heart that may account for the cardiac dysfunction reported in human neonates born to cocaine-abusing mothers.