Prenatal exposure to antiadrenergic antihypertensive drugs: effects on neurobehavioral development and the behavioral consequences of enriched rearing.
One of the beta blockers propranolol (5 or 20 mg/kg) or atenolol (5 or 20 mg/kg) or the alpha-2 agonist clonidine (20 or 100 micrograms/kg) was administered in the drinking water to pregnant Wistar rats over gestation days 1 to 21. Maternal weight gain, litter size or litter weight were unaffected as were a number of measures of physical and behavioral development. The rats were raised after weaning in either enriched or impoverished housing. At maturity, male but not female rats that had been prenatally exposed to either of the three drugs weighed less than the controls. Testing for cognitive function using an automated version of the Hebb-Williams maze indicated impaired spatial maze problem solving ability for female rats that had been exposed to propranolol (20 mg/kg) and raised in impoverishment. Generally, enriched-reared rats committed fewer errors on the maze problems. Prenatal exposure to the drugs did not alter the beneficial effects of enriched rearing on maze solving. However, clonidine-exposed (100 micrograms/kg) female rats that were raised in enrichment showed a significantly increased mortality rate. Thus, prenatal exposure to all of these drugs exerted effects which were latent, appearing in adulthood, and which were to some extent precipitated by environmental factors. We conclude that these drugs may be physical and behavioral teratogens for the rat.
Ryan
C L
CL
Department of Psychology, Carleton University, Ottawa, Ontario, Canada.
Pappas
B A
BA
D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity*; D001262:Atenolol / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects*; D003000:Clonidine / Q000633:toxicity; D003071:Cognition / Q000187:drug effects; D005260:Female; D008297:Male; D008431:Maternal-Fetal Exchange; D009420:Nervous System / Q000187:drug effects / Q000254:growth & development; D011247:Pregnancy; D011433:Propranolol / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013565:Sympatholytics / Q000633:toxicity*; D013723:Teratogens
D000959:Antihypertensive Agents; D013565:Sympatholytics; D013723:Teratogens; D001262:Atenolol; D011433:Propranolol; D003000:Clonidine