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Published on: November 21, 2012
Recovery of presynaptic dopaminergic functioning in rats treated with neurotoxic doses of methamphetamine
1Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA.
Abstract:
Repeated administration of methamphetamine (METH) to animals can result in long-lasting decreases in striatal dopamine (DA) content. In addition, the evoked overflow of striatal DA is reduced in rats 1 week after neurotoxic doses of METH. However, whether these functional changes in DA release are permanent or tend to recover over time has not been established. In the present study we used in vivo electrochemistry and microdialysis to examine evoked overflow of DA in the striatum of METH-treated rats at several time points after treatment to determine if DA overflow would spontaneously recover. Male Fischer-344 rats were administered METH (5 mg/kg, s.c. ) or saline four times in one day at 2 hr intervals. In vivo electrochemistry experiments in anesthetized rats, and in vivo microdialysis studies in awake rats, were carried out 1 week, 1 month, 6 months, and 12 months after treatment. At 1 week after treatment there were significant decreases in potassium- and amphetamine-evoked overflow of DA, and in clearance of DA, in the striatum of the METH-treated animals. Basal extracellular levels of DA and its metabolites were also decreased. Evoked overflow had partially recovered by 1 month. By 6 months evoked overflow of DA appeared to be normal in the METH-treated rats. However, whole tissue levels of striatal DA were still significantly decreased. All parameters were back to control values by 12 months. These results suggest that presynaptic dopaminergic functioning can recover to normal levels in the striatum of METH-treated rats by 12 months after treatment.
Insights
Methamphetamine (METH) causes long-term dopamine (DA) depletion in rat striatum. However, this study shows that DA overflow function recovers by 12 months after METH treatment, indicating potential for functional recovery.
Area of Science:
- Neuroscience
- Pharmacology
- Neurochemistry
Background:
- Repeated methamphetamine (METH) administration causes persistent decreases in striatal dopamine (DA).
- Previous studies show reduced striatal DA overflow 1 week after METH, but long-term recovery is unknown.
Purpose of the Study:
- To investigate the spontaneous recovery of striatal dopamine overflow after repeated METH administration.
- To determine the time course of functional changes in DA release following METH neurotoxicity.
Main Methods:
- Male Fischer-344 rats received METH (5 mg/kg) or saline four times daily.
- In vivo electrochemistry and microdialysis assessed DA overflow, clearance, and basal levels at 1 week, 1, 6, and 12 months post-treatment.
Main Results:
- METH treatment significantly decreased DA overflow and clearance at 1 week.
- Partial recovery of DA overflow was observed by 1 month, with near-normal levels by 6 months.
- Whole tissue DA levels remained decreased at 6 months but normalized by 12 months, along with all other parameters.
Conclusions:
- Presynaptic dopaminergic function in the striatum shows significant recovery over 12 months following repeated METH administration.
- While DA overflow normalizes earlier, complete recovery of DA content takes up to a year.
