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Methamphetamine self-administration is associated with persistent biochemical alterations in striatal and cortical dopaminergic terminals in the rat.
- Source :
-
PloS one [PLoS One] 2010 Jan 20; Vol. 5 (1), pp. e8790. Date of Electronic Publication: 2010 Jan 20. - Publication Year :
- 2010
-
Abstract
- Methamphetamine (meth) is an illicit psychostimulant that is abused throughout the world. Repeated passive injections of the drug given in a single day or over a few days cause significant and long-term depletion of dopamine and serotonin in the mammalian brain. Because meth self-administration may better mimic some aspects of human drug-taking behaviors, we examined to what extent this pattern of drug treatment might also result in damage to monoaminergic systems in the brain. Rats were allowed to intravenously self-administer meth (yoked control rats received vehicle) 15 hours per day for 8 days before being euthanized at either 24 hours or at 7 and 14 days after cessation of drug taking. Meth self-administration by the rats was associated with a progressive escalation of daily drug intake to 14 mg/kg per day. Animals that self-administered meth exhibited dose-dependent decreases in striatal dopamine levels during the period of observation. In addition, there were significant reductions in the levels of striatal dopamine transporter and tyrosine hydroxylase proteins. There were also significant decreases in the levels of dopamine, dopamine transporter, and tyrosine hydroxylase in the cortex. In contrast, meth self-administration caused only transient decreases in norepinephrine and serotonin levels in the two brain regions, with these values returning to normal at seven days after cessation of drug taking. Importantly, meth self-administration was associated with significant dose-dependent increases in glial fibrillary acidic protein in both striatum and cortex, with these changes being of greater magnitude in the striatum. These results suggest that meth self-administration by rats is associated with long-term biochemical changes that are reminiscent of those observed in post-mortem brain tissues of chronic meth abusers.
- Subjects :
- Animals
Cerebral Cortex drug effects
Corpus Striatum drug effects
Dopamine Plasma Membrane Transport Proteins metabolism
Glial Fibrillary Acidic Protein metabolism
Methamphetamine pharmacology
Rats
Self Administration
Serotonin metabolism
Tyrosine 3-Monooxygenase metabolism
Cerebral Cortex metabolism
Corpus Striatum metabolism
Dopamine metabolism
Methamphetamine administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 5
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 20098750
- Full Text :
- https://doi.org/10.1371/journal.pone.0008790