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Restraint as a stressor in mice: against the dopaminergic neurotoxicity of D-MDMA - low body weight mitigates restraint-induced hypothermia and consequent neuroprotection.

Authors
Johnson-EA; Sharp-DS; Miller-DB
Source
Brain Res 2000 Sep; 875(1-2):107-118
NIOSHTIC No.
20020711
Abstract
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.
Keywords
Laboratory-animals; Animals; Animal-studies; Neurotoxins; Neurotoxicity; Neurotoxic-effects; Stress; Nervous-system-disorders; Physiological-stress
Contact
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
CODEN
BRREAP
Publication Date
20000901
Document Type
Journal Article
Email Address
edj2@cdc.gov
Fiscal Year
2000
NTIS Accession No.
NTIS Price
Issue of Publication
12
ISSN
0006-8993
NIOSH Division
HELD
Source Name
Brain Research
State
WV
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