title: Effects of perinatal methylphenidate (MPH) treatment on postweaning behaviors of male and female Sprague-Dawley rats.
abstract: Methylphenidate (MPH) is a common treatment for adult Attention Deficit Hyperactivity Disorder (ADHD). However, little information exists regarding its safety during pregnancy and thus, women with ADHD face difficult decisions regarding continued use during pregnancy. Thus, Sprague-Dawley rats were orally treated 3×/day with 0 (control), 6 (low), 18 (mid), or 42 (high) mg MPH/kg/day (i.e., 0, 2, 6, or 14mg/kg at each treatment time) on gestational days 6-21. All offspring/litter were orally treated with the same dose their dam had received on postnatal days (PNDs) 1-21. After weaning, offspring were assessed for adolescent play behavior, locomotor activity, motor coordination, Barnes maze performance, acoustic startle response, novel object recognition, residential running wheel activity, flavored solution intake, home cage behavior, water maze performance, elevated plus maze behavior, locomotor response to an MPH challenge, and passive avoidance. At euthanasia, whole brain and striatal weights as well as serum hormone levels were measured. Body weights of the high MPH group were reduced in both sexes. Males of the high MPH group were less active than control males in open field assessments on PNDs 40-42. Latency to maximum acoustic startle was significantly altered in females of the medium and high MPH groups and residential running wheel activity of females of the low and medium MPH groups was lower than control females. Open arm entries in the elevated plus maze were increased in subjects of the medium MPH group. Females of the low MPH group were less sensitive to the locomotor-increasing effects of an acute 5mg/kg MPH challenge. Serum hormone levels and whole brain and striatal weights were not altered by prior MPH treatment. These results indicate that MPH treatment during development has sporadic effects on postweaning behaviors and those effects were generally exhibited by females.
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, United States. Electronic address: Sherry.Ferguson@fda.hhs.gov.
authors.forename: Sherry A
authors.initials: SA
authors.lastname: Ferguson
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, United States.
authors.forename: C
authors.initials: C
authors.lastname: Delbert Law
authors.affiliation: Pediatric and Maternal Health Staff, Office of New Drugs, Center for Drug Evaluation Research, Food and Drug Administration, Silver Spring, MD 20993, United States.
authors.forename: Leyla
authors.initials: L
authors.lastname: Sahin
authors.affiliation: Division of Epidemiology II, Office of Pharmacovigilance and Epidemiology, Office of Surveillance and Epidemiology, Center for Drug Evaluation Research, Food and Drug Administration, Silver Spring, MD 20993, United States.
authors.forename: Susan V
authors.initials: SV
authors.lastname: Montenegro
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006702:Homing Behavior / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008774:Methylphenidate / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D055139:Sensory Gating / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate
keywords: Behavior; Hormone; Methylphenidate; Pregnancy; Rat; Ritalinic acid