Methamphetamine-induced spectrin proteolysis in the rat striatum

Robert D. Staszewski, Bryan Yamamoto

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Methamphetamine (METH) is a widely abused psychostimulant. Multiple high doses of METH cause long-term toxicity to dopamine (DA) and serotonin (5-HT) nerve terminals in the brain, as evidenced by decreases in DA and 5-HT content, decreases in tyrosine and tryptophan hydroxylase activities, decreases in DA and 5-HT re-uptake sites, and nerve terminal degeneration. Multiple high doses of METH are known to elicit a rapid increase in DA release and hyperthermia. Although METH also produces a delayed and sustained rise in glutamate, no studies have shown whether METH produces structural evidence of excitotoxicity in striatum, or identified the receptors that mediate this toxicity directly, independent of alterations in METH-induced hyperthermia. These experiments investigated whether METH can cause excitotoxicity as evidenced by cytoskeletal protein breakdown in a glutamate receptor-dependent manner. METH increased calpain-mediated spectrin proteolysis in the rat striatum 5 and 7 days after METH administration without affecting caspase 3-dependent spectrin breakdown. This effect was completely blocked with the α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) receptor antagonist, GYKI 52466, but not the NMDA receptor antagonist, MK-801. However, AMPA or NMDA receptor antagonism did not attenuate the METH-induced depletions of the dopamine transporter (DAT). Independent mechanisms involved in mediating spectrin proteolysis and DAT protein loss are discussed.

Original languageEnglish (US)
Pages (from-to)1267-1276
Number of pages10
JournalJournal of Neurochemistry
Volume96
Issue number5
DOIs
StatePublished - Mar 2006
Externally publishedYes

Fingerprint

Proteolysis
Spectrin
Methamphetamine
Rats
Dopamine
Serotonin
Dopamine Plasma Membrane Transport Proteins
AMPA Receptors
N-Methyl-D-Aspartate Receptors
Toxicity
Tryptophan Hydroxylase
Nerve Degeneration
Induced Hyperthermia
Calpain
Cytoskeletal Proteins
Dizocilpine Maleate
Glutamate Receptors
Tyrosine 3-Monooxygenase
Caspase 3
Glutamic Acid

Keywords

  • Calpain
  • Excitotoxicity
  • Glutamate
  • Methamphetamine
  • Spectrin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Methamphetamine-induced spectrin proteolysis in the rat striatum. / Staszewski, Robert D.; Yamamoto, Bryan.

In: Journal of Neurochemistry, Vol. 96, No. 5, 03.2006, p. 1267-1276.

Research output: Contribution to journalArticle

@article{fe88cc1305b04e0fa94adf274eb315d2,
title = "Methamphetamine-induced spectrin proteolysis in the rat striatum",
abstract = "Methamphetamine (METH) is a widely abused psychostimulant. Multiple high doses of METH cause long-term toxicity to dopamine (DA) and serotonin (5-HT) nerve terminals in the brain, as evidenced by decreases in DA and 5-HT content, decreases in tyrosine and tryptophan hydroxylase activities, decreases in DA and 5-HT re-uptake sites, and nerve terminal degeneration. Multiple high doses of METH are known to elicit a rapid increase in DA release and hyperthermia. Although METH also produces a delayed and sustained rise in glutamate, no studies have shown whether METH produces structural evidence of excitotoxicity in striatum, or identified the receptors that mediate this toxicity directly, independent of alterations in METH-induced hyperthermia. These experiments investigated whether METH can cause excitotoxicity as evidenced by cytoskeletal protein breakdown in a glutamate receptor-dependent manner. METH increased calpain-mediated spectrin proteolysis in the rat striatum 5 and 7 days after METH administration without affecting caspase 3-dependent spectrin breakdown. This effect was completely blocked with the α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) receptor antagonist, GYKI 52466, but not the NMDA receptor antagonist, MK-801. However, AMPA or NMDA receptor antagonism did not attenuate the METH-induced depletions of the dopamine transporter (DAT). Independent mechanisms involved in mediating spectrin proteolysis and DAT protein loss are discussed.",
keywords = "Calpain, Excitotoxicity, Glutamate, Methamphetamine, Spectrin",
author = "Staszewski, {Robert D.} and Bryan Yamamoto",
year = "2006",
month = "3",
doi = "10.1111/j.1471-4159.2005.03618.x",
language = "English (US)",
volume = "96",
pages = "1267--1276",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Methamphetamine-induced spectrin proteolysis in the rat striatum

AU - Staszewski, Robert D.

AU - Yamamoto, Bryan

PY - 2006/3

Y1 - 2006/3

N2 - Methamphetamine (METH) is a widely abused psychostimulant. Multiple high doses of METH cause long-term toxicity to dopamine (DA) and serotonin (5-HT) nerve terminals in the brain, as evidenced by decreases in DA and 5-HT content, decreases in tyrosine and tryptophan hydroxylase activities, decreases in DA and 5-HT re-uptake sites, and nerve terminal degeneration. Multiple high doses of METH are known to elicit a rapid increase in DA release and hyperthermia. Although METH also produces a delayed and sustained rise in glutamate, no studies have shown whether METH produces structural evidence of excitotoxicity in striatum, or identified the receptors that mediate this toxicity directly, independent of alterations in METH-induced hyperthermia. These experiments investigated whether METH can cause excitotoxicity as evidenced by cytoskeletal protein breakdown in a glutamate receptor-dependent manner. METH increased calpain-mediated spectrin proteolysis in the rat striatum 5 and 7 days after METH administration without affecting caspase 3-dependent spectrin breakdown. This effect was completely blocked with the α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) receptor antagonist, GYKI 52466, but not the NMDA receptor antagonist, MK-801. However, AMPA or NMDA receptor antagonism did not attenuate the METH-induced depletions of the dopamine transporter (DAT). Independent mechanisms involved in mediating spectrin proteolysis and DAT protein loss are discussed.

AB - Methamphetamine (METH) is a widely abused psychostimulant. Multiple high doses of METH cause long-term toxicity to dopamine (DA) and serotonin (5-HT) nerve terminals in the brain, as evidenced by decreases in DA and 5-HT content, decreases in tyrosine and tryptophan hydroxylase activities, decreases in DA and 5-HT re-uptake sites, and nerve terminal degeneration. Multiple high doses of METH are known to elicit a rapid increase in DA release and hyperthermia. Although METH also produces a delayed and sustained rise in glutamate, no studies have shown whether METH produces structural evidence of excitotoxicity in striatum, or identified the receptors that mediate this toxicity directly, independent of alterations in METH-induced hyperthermia. These experiments investigated whether METH can cause excitotoxicity as evidenced by cytoskeletal protein breakdown in a glutamate receptor-dependent manner. METH increased calpain-mediated spectrin proteolysis in the rat striatum 5 and 7 days after METH administration without affecting caspase 3-dependent spectrin breakdown. This effect was completely blocked with the α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) receptor antagonist, GYKI 52466, but not the NMDA receptor antagonist, MK-801. However, AMPA or NMDA receptor antagonism did not attenuate the METH-induced depletions of the dopamine transporter (DAT). Independent mechanisms involved in mediating spectrin proteolysis and DAT protein loss are discussed.

KW - Calpain

KW - Excitotoxicity

KW - Glutamate

KW - Methamphetamine

KW - Spectrin

UR - http://www.scopus.com/inward/record.url?scp=33645106887&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645106887&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2005.03618.x

DO - 10.1111/j.1471-4159.2005.03618.x

M3 - Article

C2 - 16417574

AN - SCOPUS:33645106887

VL - 96

SP - 1267

EP - 1276

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 5

ER -