Neuroprotective effects of olanzapine on methamphetamine-induced neurotoxicity are associated with an inhibition of hyperthermia and prevention of Bcl-2 decrease in rats.
It is hypothesized that atypical antipsychotic drugs have neuroprotective effects which may be one of the mechanisms in treatment of schizophrenia. We investigated the neuroprotective effects of olanzapine (OLA), an atypical antipsychotic drug, on methamphetamine (METH)-induced neurotoxicity in rats. After pretreatment with OLA (2 mg/kg/day) by intraperitoneal injection for 2 weeks, rats were administered METH (7.5 mg/kg, four times at 2-h intervals) by subcutaneous injection while their body temperature was monitored. The rats were sacrificed 24 h after the last injection of METH for immunohistochemistry. METH-induced 24 h mortality was effectively reduced and METH-induced decrease of tyrosine hydroxylase immunoreactivity in caudate putamen (CPu) was significantly attenuated by OLA chronic pretreatment. Furthermore, we showed that the above neuroprotective potential of OLA might be associated with its attenuating effects on METH-induced hyperthermia and with its preventative actions on METH-induced decrease of Bcl-2, an anti-apoptotic gene product, in the CPu. Our results suggest that OLA may be a neuroprotective agent and that its neuroprotective potential may contribute to its therapeutic effects in treatment of schizophrenia.
Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, 103 Wiggins Road, Saskatoon, Canada SK S7N 5E4.
Jue
J
He
Haiyun
H
Xu
Yi
Y
Yang
Xia
X
Zhang
Xin-Min
XM
Li
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology*; D001927:Brain Diseases / Q000139:chemically induced / Q000517:prevention & control*; D004298:Dopamine / Q000378:metabolism; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control*; D007150:Immunohistochemistry; D008297:Male; D008694:Methamphetamine; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins; D000077152:Olanzapine; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism
D018696:Neuroprotective Agents; D009498:Neurotoxins; D019253:Proto-Oncogene Proteins c-bcl-2; D001569:Benzodiazepines; D008694:Methamphetamine; D014446:Tyrosine 3-Monooxygenase; D000077152:Olanzapine; D004298:Dopamine