Behavioral and biochemical studies in rats following prenatal treatment with beta-adrenoceptor antagonists.
Increased motor activity and poor performance in the active avoidance test were observed in the offspring of rats treated with dl-propranolol or sotalol during pregnancy, but not with atenolol and d-propranolol. All substances were administered in drinking water from days 8-22 of gestation. A significant increase in the density of muscarinic acetylcholine receptors in the hippocampus was found for dl-propranolol and sotalol, at 35 and 20 days of age, respectively. Twenty-day-old pups born to dl-propranolol-treated rats exhibited a non-significant decrease in the number of beta-adrenoceptors in the frontal cortex. Assuming that all the beta-adrenoceptor antagonists tested had access to the developing fetal brain, the effect of dl-propranolol and sotalol on behavior could stem from central beta 2-adrenoceptor blockade. In view of the lack of behavioral changes after atenolol, a beta 1-selective adrenoceptor antagonist, it is suggested that the clinical use of beta 1-selective adrenoceptor antagonists during pregnancy might be safer for the fetus than beta 2-adrenoceptor antagonists.
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel.
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Speiser
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Gordon
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Rehavi
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Gitter
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001262:Atenolol / Q000008:administration & dosage / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects*; D001724:Birth Weight / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011297:Prenatal Exposure Delayed Effects; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013015:Sotalol / Q000008:administration & dosage / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D001262:Atenolol; D011433:Propranolol; D013015:Sotalol