Long-term effects of a high-dose methamphetamine regimen on subsequent methamphetamine-induced dopamine release in vivo.

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.