Fetal terbutaline exposure causes selective postnatal increases in cerebellar alpha-adrenergic receptor binding.
beta-Adrenergic agonists used in therapy of premature labor and asthma cross the placenta and can affect development of the fetal nervous system. In the current study, pregnant rats were given 10 mg/kg of terbutaline on gestational days 17, 18 and 19 and adrenergic receptor binding capabilities examined in brain regions of the offspring. Despite the absence of body or brain growth impairment, selective increases were seen postnatally in cerebellar alpha 1- and alpha 2-receptor subtypes, whereas the same receptor populations were decreased by small amounts in cerebral cortex and midbrain + brainstem. beta-Adrenergic receptors showed little or no change in any region. The regional and subtype selectivity are compatible with primary deficits in the development of noradrenergic projections to the cerebellum identified in previous studies and provide further evidence that therapeutic use of beta-adrenergic agonists may produce neurobehavioral teratology.
Slotkin
T A
TA
Department of Pharmacology Duke University Medical Center, Durham, North Carolina 27710.
Kudlacz
E M
EM
Lappi
S E
SE
Tayyeb
M I
MI
Seidler
F J
FJ
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D008636:Mesencephalon / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D013726:Terbutaline / Q000494:pharmacology / Q000633:toxicity*
D011942:Receptors, Adrenergic, alpha; D013726:Terbutaline