Transient postnatal elevation of norepinephrine content and turnover in brain regions of rats exposed to terbutaline prenatally: evidence for autoregulation of noradrenergic development?
Terbutaline, a beta-adrenergic agonist used to arrest premature labor, crosses the placenta to affect fetal nervous system development. In the current study, pregnant rats were given 10 mg/kg of terbutaline on gestational days 17, 18 and 19 and the development of noradrenergic neuronal activity was assessed in brain regions of the offspring by measuring norepinephrine content and turnover. For the latter measure, animals of different ages were given a single injection of alpha-methyl-p-tyrosine, an inhibitor of norepinephrine biosynthesis, and the decline in transmitter levels evaluated in the ensuing 2.5 hr period. Body and brain region weights were unaffected by prenatal terbutaline exposure, and norepinephrine content was unaltered during the period of drug administration. Nevertheless, the terbutaline-treated animals showed a transient elevation of both norepinephrine content and turnover in the immediate postnatal period. On postnatal day 2, turnover was increased by 50% throughout the brain, whereas effects on content were much smaller; this disparity suggests that terbutaline primarily alters nerve impulse activity (which would affect turnover more than content) rather than accelerating synaptogenesis (which would increase content equivalently to, or more than turnover). Values returned to normal by postnatal day 4 and remained so through the end of the period of synaptogenesis (day 21). The transient effects of terbutaline stand in contrast to the prolonged, and ultimately adverse effects of other drugs used in prematurity, notably glucocorticoids, and are likely to reflect a naturally-occurring, positive trophic influence of beta-adrenergic stimulation on noradrenergic development.
Slotkin
T A
TA
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Seidler
F J
FJ
D000818:Animals; D000831:Animals, Newborn / Q000097:blood*; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D007279:Injections, Subcutaneous; D008636:Mesencephalon / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016548:Prosencephalon / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013726:Terbutaline / Q000008:administration & dosage / Q000494:pharmacology*
D013726:Terbutaline; D009638:Norepinephrine