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Multiple methamphetamine injections induce marked increases in extracellular striatal dopamine which correlate with subsequent neurotoxicity.
- Source :
-
Brain research [Brain Res] 1991 Nov 15; Vol. 564 (2), pp. 256-60. - Publication Year :
- 1991
-
Abstract
- Acutely, methamphetamine (m-AMPH) is known to stimulate a net efflux of dopamine (DA) in the striatum while inhibiting DA uptake, thus producing high extracellular concentrations of DA. Repeated administration of m-AMPH has been shown to damage DA terminals in the striatum. However, little direct information exists about the relationship between m-AMPH-induced DA overflow and neurotoxicity. In the present study, we used in vivo microdialysis to explore this topic. Four, but not 3, injections of m-AMPH (4 mg/kg, sc, at 2 h intervals) damaged striatal DA terminals as measured by a 43-51% decrease in post mortem striatal DA content 1 week later. Striatal microdialysis in awake animals during the course of m-AMPH treatment showed that DA overflow increased after each m-AMPH injection, but that approximately 1.5 h after the fourth m-AMPH injection, a striking increase in DA overflow occurred that was significantly larger than that seen after any of the previous 3 injections. Additionally, in animals receiving 4 injections of m-AMPH, cumulative DA overflow was negatively correlated with striatal DA content 1 week later (r = -0.74, P less than 0.05), suggesting that the substantial DA overflow seen after the fourth m-AMPH injection is especially important in m-AMPH neurotoxicity.
- Subjects :
- 3,4-Dihydroxyphenylacetic Acid metabolism
Animals
Caudate Nucleus drug effects
Caudate Nucleus metabolism
Corpus Striatum drug effects
Dialysis
Extracellular Space drug effects
Male
Methamphetamine administration & dosage
Methamphetamine toxicity
Nervous System Diseases physiopathology
Putamen drug effects
Putamen metabolism
Rats
Rats, Inbred Strains
Corpus Striatum metabolism
Dopamine metabolism
Extracellular Space metabolism
Methamphetamine pharmacology
Nervous System Diseases chemically induced
Subjects
Details
- Language :
- English
- ISSN :
- 0006-8993
- Volume :
- 564
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 1810626
- Full Text :
- https://doi.org/10.1016/0006-8993(91)91461-9