Neuronal damage and degeneration in the rat forebrain was characterized by B4
isolectin and
Fluoro-Jade labeling techniques after 4 doses of 15 mg/kg
amphetamine i.p. in 70- and 180-day-old Sprague-Dawley rats. In
amphetamine-dosed rats some seizure activity occurred in all rats exhibiting pronounced
hyperthermia but the degree of seizure activity varied greatly between individual rats. Over 90% of the rats in both age groups that showed behavioral signs of limbic
seizures had somatic degeneration in the taenia tecta within 3 days of
amphetamine exposure. Degenerating small star-shaped cells were seen in the septum and hippocampus in 70-day-old rats having extensive seizure activity. Although somatic degeneration only sporadically occurred in the piriform cortex of the younger rats, extensive B4
isolectin binding to activated microglia was observed in this area. In older rats prominent somatic degeneration was seen in the piriform cortex and orbital and insular areas of the frontal cortex of rats having
seizures. Damage to the basal ganglia and related areas, including the thalamus, parietal cortex and dorsal medial striatum, occurred in rats with pronounced
hyperthermia but only correlated with
seizures in older rats. In the more severe cases of thalamic damage the highest density of neurodegeneration was localized perivascularly. Thus,
amphetamine can produce notable damage to the limbic system when
seizures occur and to the basal ganglia and related areas when
hyperthermia occurs but the neurotoxicity profiles in these areas are age-dependent and not produced solely by
hyperthermia. Further studies to determine whether neuronal damage is the result of or the cause of
amphetamine-induced
seizures are necessary.