NEURONAL DEGENERATION IN RAT FOREBRAIN RESULTING FROM D-AMPHETAMINE-INDUCED CONVULSIONS IS DEPENDENT ON SEIZURE SEVERITY AND AGE

Neuronal damage and degeneration in the rat forebrain was characterize d 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 a ge 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 hip pocampus in 70-day-old rats having extensive seizure activity. Althoug h somatic degeneration only sporadically occurred in the piriform cort ex of the younger rats, extensive B4 isolectin binding to activated mi croglia was observed in this area. In older rats prominent somatic deg eneration was seen in the piriform cortex and orbital and insular area s of the frontal cortex of rats having seizures. Damage to the basal g anglia 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 ca ses of thalamic damage the highest density of neurodegeneration was lo calized perivascularIy. Thus, amphetamine can produce notable damage t o the limbic system when seizures occur and to the basal ganglia and r elated areas when hyperthermia occurs but the neurotoxicity profiles i n these areas are age-dependent and not produced solely by hyperthermi a. Further studies to determine whether neuronal damage is the result of or the cause of amphetamine-induced seizures are necessary. (C) 199 8 Elsevier Science B.V. All rights reserved.