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Long-term effects of a high-dose methamphetamine regimen on subsequent methamphetamine-induced dopamine release in
K E Sabol1, J T Roach, S L Broom
1Department of Psychology, University of Mississippi, 205 Peabody Building, University, MS 38677, USA. ksabol@olemiss.edu
Abstract:
Rats were treated with a high-dose methamphetamine (METH) regimen (40 mg/kg/injection, four times at 2-h intervals) or a saline regimen (four injections at 2-h intervals). Temperature related measures taken during the high-dose METH treatment were maximum core temperature and minimum chamber temperature. Fourteen rats (METH N=7; Saline N=7) were implanted with in-vivo dialysis probes 4-7 weeks post-regimen (average=6 weeks). The next day, they received a challenge dose of METH (4.0 mg/kg) and dopamine release was measured. Results showed a significant decrease in challenge-induced dopamine release in rats previously treated with the high-dose METH regimen. These findings demonstrate a functional deficit in the dopamine system 6 weeks after high-dose METH treatment. Temperature-related measures taken during the high-dose regimen were not correlated with METH-induced dopamine release 6 weeks later. An additional group of rats were sacrificed 6 weeks after the high-dose regimen (METH N=12; Saline N=10), and their brains was analyzed for dopamine and serotonin concentrations. Tissue concentrations of dopamine were significantly depleted in striatum and nucleus accumbens/olfactory tubercle, but not septum, hypothalamus, or ventral mid-brain 6 weeks after the high-dose regimen. Tissue concentrations of serotonin were also significantly depleted in striatum, nucleus accumbens/olfactory tubercle, hippocampus, somatosensory cortex, but not septum, hypothalamus or ventral mid-brain. Significant correlations between the temperature-related measures and post-mortem neurotransmitter tissue concentrations were region and transmitter dependent.
Insights
High-dose methamphetamine (METH) exposure in rats caused a significant decrease in dopamine release six weeks later. This study reveals long-term functional deficits in the dopamine system following METH treatment.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Methamphetamine (METH) is a potent psychostimulant with known neurotoxic effects.
- Understanding the long-term consequences of METH abuse on neurotransmitter systems is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the long-term functional and neurochemical effects of high-dose METH exposure on the dopamine and serotonin systems in rats.
- To determine if hyperthermia during METH treatment correlates with subsequent neurochemical changes.
Main Methods:
- Rats received high-dose METH (40 mg/kg) or saline, with core body temperature monitored.
- Six weeks post-treatment, in-vivo dialysis measured dopamine release after a METH challenge.
- Brain tissue analysis quantified dopamine and serotonin concentrations in various regions.
Main Results:
- High-dose METH treatment significantly reduced dopamine release in response to a challenge dose six weeks later.
- Dopamine depletions were observed in the striatum and nucleus accumbens/olfactory tubercle.
- Serotonin depletions were found in the striatum, nucleus accumbens/olfactory tubercle, hippocampus, and somatosensory cortex.
Conclusions:
- High-dose METH exposure induces persistent functional deficits in the dopamine system.
- Significant long-term depletions in both dopamine and serotonin occur in specific brain regions.
- Temperature changes during METH administration did not correlate with later dopamine release or neurotransmitter concentrations.