P75(NTR) is a common
neurotrophin receptor which binds all
neurotrophins with similar affinities and has been shown to be capable of mediating programmed cell death. In this study, we investigated effects of the
antipsychotic drugs (APDs)
haloperidol,
clozapine,
quetiapine, and
risperidone on p75(NTR)
mRNA levels in PC12 cells.
Haloperidol is a prototype of typical APDs, and the other three drugs are atypical APDs, which are effective in reducing negative symptoms and cognitive deficits of
schizophrenia, cause less side effects, and are more tolerable compared to
haloperidol. PC12 cells were cultured with various concentrations of
haloperidol,
clozapine,
quetiapine, or
risperidone, in their media. After culture for 48h, the cell viabilities and p75(NTR)
mRNA levels were measured. It was shown that both
haloperidol and the atypical APDs used in this study deceased p75(NTR)
mRNA levels in PC12 cells in a dose dependent manner, while not affecting cell viabilities. In further experiments, doses that produced significant/greatest effects were chosen and provided in the
culture media for various periods. Decreases in p75(NTR)
mRNA levels were observed in cultures treated for 12h with
quetiapine, 24h with
clozapine or
risperidone, or for 48h with
haloperidol. These results suggest that both
haloperidol and atypical APDs have the same action of decreasing p75(NTR)
mRNA levels in PC12 cells. Although the underlying molecular mechanism of this action remains to be elucidated, this finding is particularly relevant given the neurodevelopmental deficits associated with
schizophrenia and important roles of p75(NTR) in mediating cell death.