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Phenobarbital and dizocilpine can block methamphetamine-induced neurotoxicity in mice by mechanisms that are independent of thermoregulation.

Authors
Bowyer-JF; Holson-RR; Miller-DB; O'Callaghan-JP
Source
Brain Res 2001 Nov; 919(1):179-183
NIOSHTIC No.
20021680
Abstract
Body temperature profiles observed during methamphetamine (METH) exposure are known to affect dopamine and tyrosine hydroxylase (TH) levels in the striatum of mice; hyperthermia potentiates depletion while hypothermia is protective against depletions. In the current study, the doses of METH were sufficiently great that significant dopamine and TH depletions occurred even though hypothermia occurred. Four doses, administered at 2 h intervals, of 15 mg/kg (4x15 mg/kg) D-METH significantly decreased TH and dopamine levels to 50% of control in mice becoming hypothermic during dosing in a 13 degrees C environment. Phenobarbital or dizocilpine during METH exposure blocked the depletions while diazepam did not. Phenobarbital and dizocilpine did not block depletions by altering the hypothermic profiles from that observed during METH only exposure. Here we show that phenobarbital and dizocilpine can block measures of METH neurotoxicity by non-thermoregulatory mechanisms.
Keywords
Laboratory-animals; Animal-studies; Animals; Drug-abuse; Drugs; Neurotoxic-effects; Neurotoxicity; Neurotoxicology; Thermoregulation; Author Keywords: Methamphetamine; Hypothermia; Striatum; Dopamine; Neurotoxicity
Contact
Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA
CODEN
BRREAP
Publication Date
20011116
Document Type
Journal Article
Email Address
jbowyer@nctr.fda.gov
Fiscal Year
2002
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
0006-8993
NIOSH Division
HELD
Source Name
Brain Research
State
AR; NM; WV
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