Chronic stress enhances methamphetamine-induced extracellular glutamate and excitotoxicity in the rat striatum

Despina A. Tata, Bryan Yamamoto

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Striking parallels exist between the neurochemical and toxic effects of stress and methamphetamine. Despite these similarities, no studies have examined how stress may promote the toxic effects of methamphetamine (METH). The current study tested the hypothesis that chronic stress enhances METH toxicity by augmenting glutamate (GLU) release and excitotoxicity in response to METH administration. Adult male Sprague-Dawley rats were exposed to 10 days of unpredictable stress and then received either saline or METH (7.5 mg/kg, i.p., once every 2 h x four injections). Prior exposure to unpredictable stress acutely enhanced the striatal extracellular GLU concentrations in response to METH, and eventually caused proteolysis of the cytoskeleton protein spectrin. Administration of the corticosterone synthesis inhibitor, metyrapone (25 mg/kg, i.p., prior to each stressor), during unpredictable stress attenuated the enhanced striatal GLU release in response to METH, blocked spectrin proteolysis, and attenuated METH-associated toxicity measured by long-term depletions in the dopamine and serotonin tissue content as well as depletions in dopamine and serotonin transporter immunoreactivity of the striatum. In summary, prior exposure to unpredictable stress enhances METH-induced elevations of GLU in the striatum, resulting in long-term excitotoxic damage and an augmentation of damage to dopamine and serotonin terminals. These studies provide a neurochemical basis for how stress contributes to the deleterious effects of METH abuse.

Original languageEnglish (US)
Pages (from-to)325-336
Number of pages12
JournalSynapse
Volume62
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

Fingerprint

Methamphetamine
Glutamic Acid
Corpus Striatum
Spectrin
Poisons
Proteolysis
Dopamine
Serotonin
Metyrapone
Serotonin Plasma Membrane Transport Proteins
Dopamine Plasma Membrane Transport Proteins
Corticosterone
Cytoskeleton
Sprague Dawley Rats
Injections

Keywords

  • Dopamine transporter
  • Glucocorticoids
  • Metyrapone
  • Serotonin transporter
  • Spectrin proteolysis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology
  • Advanced and Specialized Nursing

Cite this

Chronic stress enhances methamphetamine-induced extracellular glutamate and excitotoxicity in the rat striatum. / Tata, Despina A.; Yamamoto, Bryan.

In: Synapse, Vol. 62, No. 5, 05.2008, p. 325-336.

Research output: Contribution to journalArticle

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