The effects of high-dose methamphetamine in the aging rat: Differential reinforcement of low-rate 72-s schedule behavior and neurochemistry

High-dose methamphetamine (METH) causes damage to the dopamine and serotoni n neurons in the brains of laboratory animals. The purpose of this report w as to determine the longterm consequences of high-dose METH treatment on be havior and neurochemistry. Rats were trained on the differential reinforcem ent of low-rate 72-s (DRL 72-s) schedule of reinforcement. Twelve weeks aft er training began (age 23 weeks), they received one or three high-dose METH regimens. Each regimen consisted of four injections of 15 mg/kg, at 2-h in tervals. Each regimen was separated by 7 weeks. A second group received MET H treatment at age 23 weeks, but behavioral training was not initiated unti l the rats reached age 60 weeks. A third group received METH treatment with out behavioral training. DRL behavior showed mild impairments 3 to 18 weeks after the onset of treatment; the impairments did not persist into middle age. At age 70 weeks, serotonin concentrations were decreased in somatosens ory cortex, occipital cortex, and hippocampus but not in other subcortical structures. Serotonin tissue concentrations were enhanced in septum and str iatum but only in rats receiving three regimens and behavioral training, Do pamine was not depleted at age 70 weeks. In three additional groups, one, t wo, or three METH regimens were administered, and tissue concentrations wer e measured 6 weeks after the last treatment (corresponding to the times of the behavioral test blocks in the DRL experiments). Serotonin depletions we re noted in cortex, hippocampus, amygdala, and striatum but not in septum, hypothalamus, nucleus accumbens/olfactory tubercle, or ventral midbrain. Do pamine was decreased in striatum and septum but not in nucleus accumbens/ol factory tubercle, amygdala, hypothalamus, or ventral midbrain. DRL 72-s sch edule impairments are attributed to serotonin depletions. Three METH regime ns did not result in greater behavioral or neurochemical deficits than one regimen.