The peroxidative DNA damage and apoptosis in methamphetamine-treated rat brain.
In this study, we investigated methamphetamine (METH)- induced peroxidative DNA damage in various regions of the rat brain. We injected METH to rats following 2 protocols. For the single administration experiment (group I), 50 mg/kg (i. p.) of METH was administered to observe the acute influence of METH. For the repeated administration experiment (group II), 10 mg/kg/day (i. p.) of METH was injected for 5 days. Immunohistochemically, peroxidative damage DNA, 8-hydroxy-2'- deoxyguanosine (8-OH-dG) was observed, and in situ apoptosis was also observed. In group I, immunoreactivity of 8-OH-dG was only enhanced in neurons of the nucleus accumben of METH-treated rats. On in situ apoptosis detection, positive findings were also enhanced in all examined parts compared to those in the control, though there were no significant increases in 8-OH-dG-immunopositive neurons except in the nucleus accumben. In group II, the nucleus accumben also showed enhanced 8-OH-dG immunopositivity compared to that in the control. There was no significant difference in apoptosis between the control and METH groups. Based on our observations, it is considered that METH induces oxidative DNA damage in the brain, especially in the nucleus accumben. However, those DNA damage might be caused differently between acute and chronic administration.
Tokunaga
Itsuo
I
Department of Forensic Medicine, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
Ishigami
Akiko
A
Kubo
Shin-ichi
S
Gotohda
Takako
T
Kitamura
Osamu
O
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000633:toxicity; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine