Document Detail


Neuroprotective effects of olanzapine on methamphetamine-induced neurotoxicity are associated with an inhibition of hyperthermia and prevention of Bcl-2 decrease in rats.
MedLine Citation:
PMID:  15276877     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jue He; Haiyun Xu; Yi Yang; Xia Zhang; Xin-Min Li
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain research     Volume:  1018     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-07-27     Completed Date:  2004-10-29     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  186-92     Citation Subset:  IM    
Affiliation:
Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, 103 Wiggins Road, Saskatoon, Canada SK S7N 5E4.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Apoptosis / drug effects
Benzodiazepines / pharmacology*
Brain Diseases / chemically induced,  prevention & control*
Dopamine / metabolism
Fever / chemically induced,  prevention & control*
Immunohistochemistry
Male
Methamphetamine
Neostriatum / drug effects*,  metabolism
Neuroprotective Agents / pharmacology*
Neurotoxins
Proto-Oncogene Proteins c-bcl-2 / drug effects*,  metabolism
Rats
Rats, Sprague-Dawley
Survival Rate
Tyrosine 3-Monooxygenase / drug effects,  metabolism
Chemical
Reg. No./Substance:
0/Neuroprotective Agents; 0/Neurotoxins; 0/Proto-Oncogene Proteins c-bcl-2; 12794-10-4/Benzodiazepines; 132539-06-1/olanzapine; 537-46-2/Methamphetamine; EC 1.14.16.2/Tyrosine 3-Monooxygenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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