Review article
The neuroprotective potential of low-dose methamphetamine in preclinical models of stroke and traumatic brain injury

https://doi.org/10.1016/j.pnpbp.2015.02.013Get rights and content
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Highlights

  • When administered acutely (within 12 hours after injury) low-dose methamphetamine significantly improves cognition and functional behavior.

  • The neuroprotective potential of methamphetamine is highly dose dependent.

  • Methamphetamine mediates dose dependent neuroprotection when administered within 12 h after severe TBI or stroke.

Abstract

Methamphetamine is a psychostimulant that was initially synthesized in 1920. Since then it has been used to treat attention deficit hyperactive disorder (ADHD), obesity and narcolepsy. However, methamphetamine has also become a major drug of abuse worldwide. Under conditions of abuse, which involve the administration of high repetitive doses, methamphetamine can produce considerable neurotoxic effects. However, recent evidence from our laboratory indicates that low doses of methamphetamine can produce robust neuroprotection when administered within 12 h after severe traumatic brain injury (TBI) in rodents. Thus, it appears that methamphetamine under certain circumstances and correct dosing can produce a neuroprotective effect. This review addresses the neuroprotective potential of methamphetamine and focuses on the potential beneficial application for TBI.

Abbreviations

ADHD
attention hyperactive disorder
AKT
protein kinase B
AMPA
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
Bcl-2
B-cell lymphoma 2
BDNF
brain derived neurotrophic factor
Css
Steady state plasma concentration
D1
type 1 dopamine receptor
D2
type 2 dopamine receptor
DAT
dopamine transporter
FDA
Food and Drug Administration
IV
intravenous
MRI
magnetic resonance imaging
NAT
norepinephrine transporter
NMDA
N-methyl-D-aspartate
OGD
oxygen glucose deprivation
PET
positron emission tomography
PI3K
phosphoinositol 3 kinase
PV
parvalbumin
RHSC
rat hippocampal slice cultures
SERT
serotonin transporter
SST
somatostatin
TBI
traumatic brain injury
USP
United States Pharmacopeia
UTD
untreated
VMAT
vesicular monoamine transporter

Keywords

Methamphetamine
Neuroportection
Stroke
Traumatic brain injury

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