title: Effects of developmental methylphenidate (MPH) treatment on monoamine neurochemistry of male and female rats.
abstract: Attention Deficit Hyperactivity Disorder (ADHD) is estimated to affect 4-5% of the adult human population (Kessler et al., 2006; Willcutt, 2012). Often prescribed to attenuate ADHD symptoms (Nair and Moss, 2009), methylphenidate hydrochloride (MPH) can have substantial positive effects. However, there is a paucity of literature regarding its use during pregnancy. Thus, adult women with ADHD face a difficult decision when contemplating pregnancy. In this study, pregnant Sprague-Dawley rats were orally treated a total of 0 (water), 6 (low), 18 (medium), or 42 (high) mg MPH/kg body weight/day (divided into three doses) on gestational days 6-21 (i.e., the low dose received 2 mg MPH/kg body weight 3×/day). Offspring were orally treated with the same daily dose as their dam (divided into two doses) on postnatal days (PNDs) 1-21. One offspring/sex/litter was sacrificed at PND 22 or PND 104 (n=6-7/age/sex/treatment group) and the striatum was quickly dissected and frozen. High Performance Liquid Chromatography (HPLC) coupled to a Photo Diode Array detector (PDA) was used to analyze monoamine content in the striatum of one side while a sandwich ELISA was used to analyze tyrosine hydroxylase (TH) from the other side. Age significantly affected monoamine and metabolite content as well as turnover ratios (i.e., DA, DOPAC, HVA, DOPAC/DA, HVA/DA, 5-HT and 5-HIAA); however, there were no significant effects of sex. Adult rats of the low MPH group had higher DA levels than control adults (p<0.05). At both ages, subjects of the low MPH group had higher TH levels than controls (p<0.05), although neither effect (i.e., higher DA or TH levels) exhibited an apparent dose-response. PND 22 subjects of the high MPH treatment group had higher ratios of HVA/DA and DOPAC/DA than same-age control subjects (p<0.05). The increased TH levels of the low MPH group may be related to the increased DA levels of adult rats. While developmental MPH treatment appears to have some effects on monoamine system development, further studies are required to determine if these alterations manifest as functional changes in behavior.
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, United States.
authors.forename: John J
authors.initials: JJ
authors.lastname: Panos
authors.affiliation: CDC-NIOSH, United States.
authors.forename: James P
authors.initials: JP
authors.lastname: O'Callaghan
authors.affiliation: CDC-NIOSH, United States.
authors.forename: Diane B
authors.initials: DB
authors.lastname: Miller
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, United States. Electronic address: Sherry.Ferguson@fda.hhs.gov.
authors.forename: Sherry A
authors.initials: SA
authors.lastname: Ferguson
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000032:analysis*; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000032:analysis; D005260:Female; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015306:Biogenic Monoamines; D008774:Methylphenidate; D004298:Dopamine
keywords: Development; Dopamine; Methylphenidate; Monoamines; Rat