Perinatal cocaine exposure reduces myocardial norepinephrine transporter function in the neonatal rat.
Norepinephrine transporter (NET) mediates the active removal of norepinephrine (NE) released from sympathetic nerve terminals via reuptake, and NET function and expression can be regulated by cocaine. NET expression and its regulation by cocaine in the developing sympathetic nervous system during early postnatal period, however, have not been examined. We quantified immunodetectable NET protein expression in the neonatal rat heart to examine the developmental pattern of myocardial NET during the first 2 weeks after birth. To assess sympathetic innervations, we simultaneously quantified the expression of myocardial tyrosine hydroxylase (TH). Timed pregnant rats received daily intragastric treatment with saline (CTL) or cocaine at 60 mg/kg (Coc) from Gestational Day 2 until parturition. After birth, nursing mothers continued to receive the same treatment. The expression of myocardial TH and NET in neonatal rats were then studied at 1 day (Postnatal Day 1, PD1), 7 days (PD7) or 14 days (PD14) of age. We observed a similar age-dependent increase in the expression for myocardial NET and TH during the first 2 weeks of postnatal life, in both CTL and Coc animals. While myocardial TH was significantly up-regulated following perinatal cocaine exposure, no significant change in immunodetectable myocardial NET protein was evident. To further examine whether NET function might be affected by perinatal cocaine exposure, we performed NE uptake in myocardial membranes from PD14 CTL and Coc rats. We found that NE uptake was reduced at PD14 in the cocaine-treated group. Our results indicate that myocardial NET and TH are both developmentally regulated. Furthermore, our results indicate that perinatal exposure to cocaine did not change NET protein expression but impaired myocardial NET function in the neonatal rat.
Zhao
Yejun
Y
Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, 622 West 168th Street, New York, NY 10032, USA. yz82@columbia.edu
Sun
Lena
L
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000378:metabolism; D003042:Cocaine / Q000633:toxicity*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000254:growth & development; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014316:Tritium / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000633:toxicity*
D050484:Norepinephrine Plasma Membrane Transport Proteins; C493226:Slc6a2 protein, rat; D027981:Symporters; D014662:Vasoconstrictor Agents; D014316:Tritium; D014446:Tyrosine 3-Monooxygenase; D003042:Cocaine; D009638:Norepinephrine