Abstract：
:Repeated abuse of stimulant drugs, cocaine and amphetamine, is associated with extraneuronal dopamine accumulation in specific brain areas. Dopamine may be cytotoxic through the generation of reactive oxygen species, namely hydrogen peroxide (H2O2), resulting from dopamine oxidative metabolism. In this work, we studied the cytotoxicity in PC12 cells (a dopaminergic neuronal model) chronically and/or acutely exposed to cocaine or amphetamine, as compared to H2O2 exposure. Chronic cocaine treatment induced sensitization to acute cocaine insult and increased cocaine-evoked accumulation of extracellular dopamine, although no changes in dihydroxyphenylacetic acid (DOPAC) levels were observed. Moreover, dopamine was depleted in cells chronically exposed to amphetamine and acute amphetamine toxicity persisted in these cells, indicating that dopamine was not involved in amphetamine cytotoxicity. PC12 cells chronically treated with H2O2 were totally resistant to acute H2O2, but not to acute cocaine or amphetamine exposure, suggesting that the toxicity induced by these stimulant drugs is unrelated to adaptation to oxidative stress. Interestingly, chronic cocaine treatment largely, but not completely, protected the cells against a H2O2 challenge, whilst a decrement in intracellular ATP was observed. This study shows that chronic treatment of PC12 cells with cocaine or H2O2 modifies the cytotoxic response to an acute exposure to these agents.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Cunha-Oliveira T,Rego AC,Morgadinho MT,Macedo T,Oliveira CRdoi
10.1016/j.tox.2005.08.022keywords:
subject
Has Abstractpub_date
2006-01-05 00:00:00pages
54-62issue
1eissn
0300-483Xissn
1879-3185pii
S0300-483X(05)00386-0journal_volume
217pub_type
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