Effects of perinatal methylphenidate (MPH) treatment in male and female Sprague-Dawley offspring.
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. Here, 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 14 mg/kg at each treatment time) on gestational days 6-21. On postnatal days (PNDs) 1-21, all offspring/litter were orally treated 2 ×/day with the same dose. Righting reflex (PNDs 3-6) and slant board performance (PNDs 8-11) were assessed. T3, T4, E2, testosterone, LH and corticosterone were measured at PND 22. Separate pregnant dams and resulting litters were used for serum MPH measurements. MPH treatment had mild, but significant, effects on gestational body weight and food intake. Birth weight of high MPH offspring was 5% more than controls (p<0.0500). Relative to same-sex controls on PNDs 1-22, low and mid MPH males weighed more (p<0.0094), low MPH females weighed more (p<0.0001), while high MPH females weighed less (p<0.0397). PND 22 serum E2 levels were significantly decreased (20-25%) in high MPH males and females (p<0.0500). Behavioral performance was unaffected by treatment. Serum MPH levels of the low MPH pregnant dams were within the range produced by therapeutic MPH doses in adults; however, offspring levels in all groups were substantially higher. These results indicate that developmental MPH treatment has mild effects on gestational body weight and food intake and offspring preweaning body weight. Potential functional consequences of decreased serum E2 levels are not clear, but may impact later behavior or physiology.
Division of Neurotoxicology, National Center for Toxicological Research, Food Drug Administration, Jefferson, AR 72079, United States.
John J
JJ
Panos
Division of Neurotoxicology, National Center for Toxicological Research, Food Drug Administration, Jefferson, AR 72079, United States.
C Delbert
CD
Law
Division of Neurotoxicology, National Center for Toxicological Research, Food Drug Administration, Jefferson, AR 72079, United States. Electronic address: Sherry.Ferguson@fda.hhs.gov.
Sherry A
SA
Ferguson
D000818:Animals; D000831:Animals, Newborn; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D001724:Birth Weight / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D004435:Eating / Q000187:drug effects; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D023421:Models, Animal; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D004958:Estradiol
Behavior; Hormone; Methylphenidate; Pregnancy; Rat; Ritalinic acid