Effects of chronic perphenazine treatment on growth and endocrine function in developing rats

To study the possible adverse effects of chronic perphenazine treatment upon growth and endocrine function in a developing animal, perphenazine (1, 10 and 25 mg/kg b.wt.) was administered to developing rats. At various intervals, body weight, naso-anal length, age at vaginal opening, number of regular estrous cycles and serum levels of follicle-stimulating hormone, luteinizing hormone, growth hormone, thyroid-stimulating hormone, prolactin, 3,5,3'-triiodothyronine and thyroxine were measured. 1) At 10 and 25 mg/kg b.wt., perphenazine significantly decreases rate of skeletal growth and body weight gain in male and female rats, primarily due to a decreased food and water intake. 2) No dose of chronic perphenazine (1, 10 or 25 mg/kg b.wt.) significantly delays vaginal patency or the age of initiation of vaginal estrus or proestrus. The age at initiation of the first regular estrous cycle, however, is significantly delayed. 3) Estrous cycles continue to be abnormal 3 months after cessation of perphenazine treatment. 4) Serum levels of 3,5,3'-triiodothyronine and thyroxine are significantly depressed in 10 and 25 mg/kg b.wt. perphenazine-treated male and female rats. 5) Serum prolactin is significantly higher in 10 and 25 mg/kg b.wt. perphenazine-treated rats. 6) Chronic perphenazine treatment (1, 10 and 25 mg/kg b.wt.) significantly increases serum thyroid-stimulating hormone levels in females, with no significant effect in male rats. 7) In males and females, chronic perphenazine treatment has no consistent effect on serum levels of luteinizing hormone, follicle-stimulating hormone or growth hormone. Thirty to 60 days after cessation of perphenazine treatment, serum levels of luteinizing hormone, follicle-stimulating hormone, prolactin, thyroid-stimulating hormone, 3,5,3'-triiodothyronine and thyroxine are normal. In conclusion, chronic perphenazine treatment during the neonatal period can significantly interfere with normal growth and endocrine function. Most of these effects, with the exception of the irregular estrous cycles, disappear after discontinuation of perphenazine administration.