Progress in Neuro-Psychopharmacology and Biological Psychiatry

Haloperidol, but not clozapine, induces dopaminergic nigrostriatal degeneration. However, the mechanisms by which haloperidol causes neurotoxicity are not fully understood. An increase in cyclooxygenase-2 (COX-2) expression has been observed correlated with nigrostriatal degeneration. We investigated the modifications of striatal and nigral COX-2 expression induced by chronic haloperidol and clozapine administration. Rats were treated for 21 days with: haloperidol (1 mg/kg), clozapine (1 mg/kg) or saline. No significant differences were observed in striatal and nigral COX-2 expression between haloperidol and clozapine-treated animals. This observation might suggest that nigral COX-2 expression is not the underlying mechanisms involved in haloperidol-induced dopaminergic neurodegeneration.