The effects of chronic methylphenidate treatment on growth and endocrine function in the developing rat

To study the possible adverse effects of chronic methylphenidate (Ritalin) upon growth and endocrine function in a developing animal, methylphenidate (1, 3, 10, 35 and 100 mg/kg b.wt.) was administered to neonatal 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, prolactin and insulin were examined. 1) At 35 and 100 mg/kg b.wt., methylphenidate significantly decreases rate of skeletal growth and body weight gain in both females and males, largely due to its anorexigenic effects. At 100 mg/kg b.wt., the inhibitory effect on skeletal growth appears to be partly independent of anorexigenic properties. 2) Vaginal patency in females given 35 and 100 mg/kg b.wt. of methylphenidate during neonatal life is significantly delayed, and number of estrous cycles after cessation of chronic treatment is significantly reduced. In juvenile females, chronic methylphenidate significantly decreases the number of estrous cycles during treatment, with no significant differences between control and treated rats in cycle regularity after cessation of drug treatment. 3) In both males and females, chronic methylphenidate depresses serum prolactin levels at all doses, an effect which disappears after cessation of treatment. 4) At all doses, chronic methylphenidate significantly decreases basal serum insulin levels, but significantly enhances the insulin response to an acute glucose challenge. 5) Chronic methylphenidate treatment significantly depresses growth hormone levels in females, with no consistent effect in males. 6) In females, chronic methylphenidate has no consistent effect upon gonadotropin levels but significantly decreases luteinizing hormone and follicle-stimulating hormone levels in males, Thus, chronic methylphenidate during the neonatal period may significantly affect growth and endocrine function of the developing rat, but some of the adverse effects are transient and occur only at higher doses.