title: Adverse effects of methylphenidate on the reproductive axis of adolescent female rats.
abstract: OBJECTIVE
  To examine the effects of chronic methylphenidate use on the reproductive axis of adolescent female rats.
  
  
  METHODS
  Controlled prospective study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Twenty prepubertal female Sprague Dawley rats.
  
  
  METHODS
  Subcutaneous implantation of drug-filled Alzet minipumps (Durect Corporation, Cupertino, CA) for infusing methylphenidate (450 microg/d, treated) or physiological saline (control) for 4 weeks. Estrous cyclicity was checked from 3 weeks of pump implantation till the termination of the experiments. Animals were killed after 4 weeks of treatment.
  
  
  METHODS
  Estrous cyclicity, pituitary and peripheral FSH and LH, serum estrogen and progesterone, ovarian histology, and immunocytochemistry for localizing growth differentiation factor-9 and activin receptors-I.
  
  
  RESULTS
  Compared with the control group, the treated animals exhibited the following: [1] poor vaginal opening and erratic estrous cyclicity; [2] undeveloped, disrupted, or prematurely luteinized ovarian follicles; [3] absence of growth differentiation factor-9 and of activin receptors I and IB in the oocyte; and [4] high levels of LH in the pituitary.
  
  
  CONCLUSIONS
  Chronic methylphenidate administration during adolescence perturbs pubertal onset, adversely affects maturation of the female reproductive axis by retarding pituitary LH release, and adversely affects ovarian folliculogenesis. These novel findings may have significant clinical implications in evaluating the effects of methylphenidate abuse on adolescent health.
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555-1062, USA. schakrab@utmb.edu
authors.forename: Shilla
authors.initials: S
authors.lastname: Chatterjee-Chakrabarty
authors.forename: Brian T
authors.initials: BT
authors.lastname: Miller
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Collins
authors.forename: Manubai
authors.initials: M
authors.lastname: Nagamani
mesh_terms: D000367:Age Factors; D000818:Animals; D030762:Estrous Cycle / Q000097:blood / Q000187:drug effects* / Q000502:physiology; D005260:Female; D008774:Methylphenidate / Q000008:administration & dosage / Q000009:adverse effects*; D010907:Pituitary Hormones / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects* / Q000502:physiology; D012741:Sexual Maturation / Q000187:drug effects* / Q000502:physiology
chemical_list: D010907:Pituitary Hormones; D008774:Methylphenidate