Restraint as a Stressor in Mice: Against the Dopaminergic Neurotoxicity of D-MDMA – Low Body Weight Mitigates Restraint-Induced Hypothermia and Consequent Neuroprotection

Details

• Personal Author:
  Johnson, Elizabeth A. ; Miller DB ; Sharp DS
• Description:
  In experimental studies of stress, restraint of laboratory rodents, perceived as easy to apply and believed to be reproducible, is a commonly used manipulation. The restraint manipulation is utilized as a technique to characterize the physiological, cellular and molecular consequences of stress as well as a tool to understand the ways in which stress may interact with toxic substances. In previous work, we utilized restraint in an examination of the effect of stress on the striatal dopaminergic neurotoxicity engendered by a series of substituted amphetamines. Contrary to our expectations, and most likely due to its body temperature-reducing properties in the mouse, restraint provided total or near total protection against the neurotoxicity of these agents. During subsequent studies utilizing C57Bl6/J female mice of varying weights and ages the degree of temperature reduction and the associated ability to block (20-100%) the dopamine depletion associated with the neurotoxic amphetamine 3,4-methylendioxyamphetamine (D-MDMA, 20 mg/kg of mouse body weight, every 2 h, s.c., total of four doses) were found to vary considerably more than had been previously observed. An in-depth analysis of the role mouse weight plays in the temperature reduction induced by restraint indicates mouse weight is a primary determinant of hypothermia and subsequent neuroprotection. It suggests the induction of stress in rodents by restraint is a complex effect that may lead to unanticipated results. The restraint manipulation is not as straight-forward a procedure as is commonly believed. Our data indicate that consistent application of restraint may require an adjustment of the restrainer device to mouse body weight. [Description provided by NIOSH]
• Subjects:
  Animals Hypothermia Laboratories Nervous System Nervous System Diseases Occupational Health Safety
• Keywords:
  Animal Studies Author Keywords: Restraint-induced Hypothermia D-MDMA D-MDMA-induced Neurotoxicity Laboratory Animals Nervous System Disorders Neuroprotection Neurotoxic Effects Neurotoxicity Neurotoxins Physiological Stress Restraint Restraint-induced Neuroprotection Stress

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• ISSN:
  0006-8993
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; 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:
  107-118
• Volume:
  875
• Issue:
  12
• NIOSHTIC Number:
  nn:20020711
• Citation:
  Brain Res 2000 Sep; 875(1-2):107-118
• Contact Point Address:
  Chronic Stress Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institue for Occupational Safety and Health, 1095 Willowdale Raod, Morgantown, WV 26505, USA
• Email:
  edj2@cdc.gov
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  True
• Source Full Name:
  Brain Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b452c37d955ae19a29ba51abd5dadadf8f296c6b6a8247eb0ca5d2e7f14828cd5155010245f675945cf6708a80b75a41367357d6e4966d5113d44bebcd9fea3d
• Download URL:
  https://stacks.cdc.gov/view/cdc/198387/cdc_198387_DS1.pdf
• File Type:
  [PDF - 371.31 KB ]