Adverse effects of methylphenidate on the reproductive axis of adolescent female rats.
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.
Chatterjee-Chakrabarty
Shilla
S
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555-1062, USA. schakrab@utmb.edu
Miller
Brian T
BT
Collins
Thomas J
TJ
Nagamani
Manubai
M
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
D010907:Pituitary Hormones; D008774:Methylphenidate