Effects of methylphenidate on the onset of puberty and reproductive system in male and female rat models

Methylphenidate (MPH) is a central nervous system stimulant, which blocks the reuptake of dopamine and noradrenaline. It is widely used to treat attention deficient hyperactivity disorder (ADHD) in children and adolescents. This study aimed to investigate the effect of chronic administration of MPH on reproductive functions in both male and female rats and the reversibility of those effects. Sprague Dawley rats from both sexes were administered with 5 mg/kg of MPH or physiological saline via oral gavage from postnatal day (PND) 21 to PND 60 and from PND 21 to PND 90. In addition, recovery groups from both sexes in which stopped receiving MPH from PND 60 to PND 90 were included. In the end of the study, the results showed slightly but significantly early puberty in male models, slight decrease in testosterone levels in treated groups to increase again in the recovery group. The histological findings showed seminiferous tubule degeneration in the testes in MPH-treated groups. Leydig and Sertoli cells were affected in the MPH-treated groups, and all the findings were improved in the recovery group. In female animals, a significant delay in puberty onset was observed. Estradiol levels were decreased in MPH-treated group up to PND 90 compared to control group and a surge in luteinizing hormone levels was detected in recovery group. Histological findings showed morphological deterioration in the basement membrane of the ovaries of MPH-treated groups, more atretic follicles were detected and these findings were improved in the ovaries of recovery group. This study demonstrates that MPH could affect the reproductive functions in both male and female rats and those effects are transient. Key words: Methylphenidate, Ovary, Puberty, Sex hormones, Testes