Prenatal cocaine exposure alters norepinephrine release from cardiac adrenergic nerve terminals.
The effect of prenatal cocaine exposure on the development of the cardiac adrenergic nervous system was assessed in neonatal rabbits. Pregnant does received cocaine (4 mg/kg, i.v., bid) or saline during gestational days 8 to 29. Hearts were obtained on postnatal days 10, 20, 30, and 50. Adrenergic nerve function was assessed by measuring 3H-norepinephrine (NE) uptake and 3H-NE release from cardiac synaptosomes. NE uptake increased with postnatal age and was not affected by cocaine exposure. K(+)-induced NE release increased with age, was significantly less in cocaine exposed rabbits compared to saline exposed rabbits at days 10, and 20, but was similar at days 30 and 50. NE release induced by ionomycin, a Ca2+ ionophore, did not change with age, was significantly greater in cocaine exposed rabbits compared to saline exposed rabbits at days 10, 20, and 30, but was similar at day 50. Wet heart weight, heart weight per body weight, and NE content of the hearts were not affected by cocaine exposure. These results suggest that prenatal cocaine exposure delays the development of the mechanisms responsible for Ca2+ influx during K(+)-induced depolarization and increases the neurosecretory response to intracellular Ca2+.
Snyder
D L
DL
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia 19129, USA.
Gayheart
P
P
Johnson
M D
MD
Gurdal
H
H
Roberts
J
J
D000320:Adrenergic Fibers / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003042:Cocaine / Q000633:toxicity*; D003891:Desipramine / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000254:growth & development / Q000294:innervation*; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011817:Rabbits; D012680:Sensitivity and Specificity; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014316:Tritium
D014316:Tritium; D015759:Ionomycin; D003042:Cocaine; D011188:Potassium; D003891:Desipramine; D009638:Norepinephrine