REPRODUCTIVE AND DEVELOPMENTAL TOXICITY STUDIES OF BUSPIRONE HYDROCHLORIDE (II) : Oral Administration to Rats During Perinatal and Lactation Periods

Abstract

Buspirone hydrochloride (buspirone), an anxiolytic drug, was administered orally to pregnant Crj: CD (Sprague-Dawley) rats from day 17 of gestation through day 20 of postpartum at dose levels of 2, 12 and 75 mg/kg/day. The summarized results obtained are as follows : 1. Decrdased activity was observed for F₀ dams at buspirone 75 mg/kg. Further, the suppression of maternal body weight gains accompanied by the reduction of food consumption was shown during the administration period at buspirone 12 mg/kg and higher. 2. Brain and adrenal weights were increased in F₀ dams at buspirone 12 mg/kg and higher. Besides, lung and pituitary weights were augmented in F₀ dams at buspirone 75 mg/kg. 3. Buspirone 75 mg/kg brought the increased number of stillbirths in F₁ neonates. 4. Buspirone 75 mg/kg lowered the viability of newborns (F₁) on postnatal day 3 and prolonged the days required for pinnae detachment, presence of abdominal hair and eye opening in offspring (F₁), but failed to function their learning ability, motility, motor activity or emotional development. 5. Body weight gains were depressed in both male and female F₁ rats at buspirone 12 mg/kg and higher. Food consumption was also decreased in both sexes at the same dose levels. 6. Heart weights were decreased in female F₁ rats after mating at buspirone 12 mg/kg and higher. Further, buspirone 75 mg/kg brought a suppression of brain weights at 10 weeks of age in male and female F₁ rats, but failed to affect their reproductive ability. 7. F₂ neonates derived from F₁ rats whose dams had ever received buspirone during the perinatal and lactation periods showed no changes in observation items at birth. Based on these results, the no-effect dose level of oral buspirone under the present experimental condition was estimated to be 2 mg/kg/day against dams and their offspring.