Effects of developmental methylphenidate (MPH) treatment on monoamine neurochemistry of male and female rats

Details

• Personal Author:
  Ferguson SA ; Miller DB ; O'Callaghan JP ; Panos JJ
• Description:
  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) mgMPH/kgbodyweight/day (divided into three doses) on gestational days 6-21 (i.e., the low dose received 2mgMPH/kgbodyweight3×/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. [Description provided by NIOSH]
• Subjects:
  Amines Animals Behavior Drug Therapy Laboratories Mental Disorders Occupational Health Pregnancy Safety Urogenital Diseases Urogenital System

  More +
• Keywords:
  Animal-studies Author Keywords: Methylphenidate Behavioral-disorders Development Developmental-disorders Dopamine Dose-response Drug-interaction Drug-therapy Laboratory-animals Laboratory-testing Monoamines Prenatal-exposure Rat Reproductive-effects Reproductive-hazards

  More +
• ISSN:
  0892-0362
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Arkansas ; OSHA Region 3 ; OSHA Region 6 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  70-74
• Volume:
  45
• NIOSHTIC Number:
  nn:20045073
• Citation:
  Neurotoxicol Teratol 2014 Sep-Oct; 45:70-74
• Contact Point Address:
  Sherry.Ferguson, Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, United States
• Email:
  Sherry.Ferguson@fda.hhs.gov
• CAS Registry Number:
  Dopamine (CAS RN 51-61-6) ; L-Tyrosine (CAS RN 55520-40-6) ; Methylphenidate (CAS RN 113-45-1) ; Ritalin (CAS RN 298-59-9)
• Federal Fiscal Year:
  2014
• Peer Reviewed:
  True
• Source Full Name:
  Neurotoxicology and Teratology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d5ce19eedacb7af03bd0a17f9df8c61f1d4d319f00076e291a54ee84961bab89874cbb829dc53a51676272516b7560667acf8168739d804b4648d46412d4d89c
• Download URL:
  https://stacks.cdc.gov/view/cdc/200605/cdc_200605_DS1.pdf
• File Type:
  [PDF - 422.79 KB ]