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 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.
Bowyer
J F
JF
Division of Neurotoxicology, HFT-132, National Center for Toxicological Research/FDA, Jefferson, AR 72079-9502, USA. jbowyer@nctr.fda.gov
Peterson
S L
SL
Rountree
R L
RL
Tor-Agbidye
J
J
Wang
G J
GJ
D000367:Age Factors; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature; D002395:Catecholamines / Q000378:metabolism; D003913:Dextroamphetamine; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology*; D018698:Glutamic Acid / Q000378:metabolism; D008032:Limbic System / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology*; D016548:Prosencephalon / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013566:Sympathomimetics
D002395:Catecholamines; D013566:Sympathomimetics; D018698:Glutamic Acid; D003913:Dextroamphetamine