Developmental toxicity of the dopamine agonist pergolide mesylate in CD-1 mice. II: Perinatal and postnatal exposure.
Pergolide mesylate is a dopamine agonist and, therefore, reduces prolactin secretion. In Experiment I, pregnant mice were given oral doses of 0, 0.1, 0.3, 1.0 or 3.0 mg/kg/day pergolide on GD 15 through PD 10 or 20 to identify a tolerated dose which would not markedly reduce offspring survival during late gestational and lactational exposure. Offspring survival was not affected at any dose, but dose-related decreases in progeny body weights occurred at weaning. On PD 10, suckling-induced increases in maternal serum prolactin concentrations did not occur in dams treated with 3.0 mg/kg/day. In Experiment II, pregnant mice were given oral doses of 0, 0.002, 0.1 or 3.0 mg/kg/day pergolide on GD 15 through PD 20. Dams were allowed to deliver and maintain their offspring throughout a 21-day lactation period. Growth and behavioral performance of one F1 male and one F1 female per litter were monitored, followed by a reproduction trial and terminal organ weight measurements. There were no treatment-related effects on maternal body weights, food consumption, or terminal organ weights and pathology. Three dams showed overt signs of mammary inflammation and lactational insufficiency and mean progeny survival was decreased slightly in the 3.0 mg/kg/day group. There were no adverse effects on growth, development or reproductive performance in the F1 treatment-derived generation. Neonatal negative geotaxis, 1-h activity levels at 30 and 60 days of age, auditory startle habituation at 55 days of age, and two-way active avoidance performance at 65 days of age were not affected significantly by treatment. Thus doses of pergolide that did not inhibit lactation completely in the F0 dams were found to have no enduring effects on offspring development.
Buelke-Sam
J
J
Toxicology Research Laboratories, Eli Lilly & Company, Greenfield, IN 46140.
Cohen
I R
IR
Tizzano
J P
JP
Owen
N V
NV
D000014:Abnormalities, Drug-Induced; D000375:Aging; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D005260:Female; D005313:Fetal Death; D008098:Litter Size / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009498:Neurotoxins; D010479:Pergolide / Q000633:toxicity*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011388:Prolactin / Q000097:blood; D012727:Sex Characteristics
D009498:Neurotoxins; D010479:Pergolide; D011388:Prolactin