TY - JOUR
T1 - Haloperidol, spiperone, pimozide and aripiprazole reduce intracellular dopamine content in PC12 cells and rat mesencephalic cultures
T2 - Implication of inhibition of vesicular transport
AU - Matsuo, Takaaki
AU - Izumi, Yasuhiko
AU - Wakita, Seiko
AU - Kume, Toshiaki
AU - Takada-Takatori, Yuki
AU - Sawada, Hideyuki
AU - Akaike, Akinori
N1 - Funding Information:
This work was supported by grants-in-aid for Scientific Research from the Japan Society for the Promotion of Science and from the Ministry of Education, Culture, Sports, Science and Technology of Japan .
PY - 2010/8
Y1 - 2010/8
N2 - Accumulating evidence suggests that antipsychotics affect dopamine release from dopaminergic neurons, but the precise mechanisms are not fully understood. Besides, there are few studies on the effects of antipsychotics on intracellular dopamine content. In this study, the effects of 8 antipsychotics on dopamine release and intracellular dopamine content in PC12 cells were investigated. Pretreatment with haloperidol, spiperone, pimozide, aripiprazole and risperidone markedly inhibited high potassium-evoked dopamine release. By contrast, pretreatment with chlorpromazine slightly increased high potassium-evoked dopamine release, while pretreatment with sulpiride and olanzapine had no effect. Haloperidol, spiperone, pimozide, chlorpromazine, aripiprazole and olanzapine evoked dopamine release, while sulpiride and risperidone had no effect. In addition, haloperidol, spiperone, pimozide, aripiprazole and risperidone reduced intracellular dopamine content in a concentration-dependent manner. These results suggest that the reduction in high potassium-evoked dopamine release by pretreatment with antipsychotics results from the reduction in vesicular dopamine content. Treatment with the 8 antipsychotics did not affect the expression of total or phosphorylated tyrosine hydroxylase. Instead, haloperidol, spiperone, pimozide and aripiprazole as well as reserpine transiently increased extracellular levels of dopamine metabolites. In addition, haloperidol, spiperone, pimozide, aripiprazole and risperidone reduced vesicular [3H]dopamine transport. These results suggest that the inhibition of vesicular dopamine transport by haloperidol, spiperone, pimozide and aripiprazole results in a reduction in vesicular dopamine content.
AB - Accumulating evidence suggests that antipsychotics affect dopamine release from dopaminergic neurons, but the precise mechanisms are not fully understood. Besides, there are few studies on the effects of antipsychotics on intracellular dopamine content. In this study, the effects of 8 antipsychotics on dopamine release and intracellular dopamine content in PC12 cells were investigated. Pretreatment with haloperidol, spiperone, pimozide, aripiprazole and risperidone markedly inhibited high potassium-evoked dopamine release. By contrast, pretreatment with chlorpromazine slightly increased high potassium-evoked dopamine release, while pretreatment with sulpiride and olanzapine had no effect. Haloperidol, spiperone, pimozide, chlorpromazine, aripiprazole and olanzapine evoked dopamine release, while sulpiride and risperidone had no effect. In addition, haloperidol, spiperone, pimozide, aripiprazole and risperidone reduced intracellular dopamine content in a concentration-dependent manner. These results suggest that the reduction in high potassium-evoked dopamine release by pretreatment with antipsychotics results from the reduction in vesicular dopamine content. Treatment with the 8 antipsychotics did not affect the expression of total or phosphorylated tyrosine hydroxylase. Instead, haloperidol, spiperone, pimozide and aripiprazole as well as reserpine transiently increased extracellular levels of dopamine metabolites. In addition, haloperidol, spiperone, pimozide, aripiprazole and risperidone reduced vesicular [3H]dopamine transport. These results suggest that the inhibition of vesicular dopamine transport by haloperidol, spiperone, pimozide and aripiprazole results in a reduction in vesicular dopamine content.
KW - Antipsychotics
KW - Dopamine release
KW - Intracellular dopamine content
KW - Vesicular transport
UR - http://www.scopus.com/inward/record.url?scp=77953806652&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2010.04.043
DO - 10.1016/j.ejphar.2010.04.043
M3 - 学術論文
C2 - 20460122
AN - SCOPUS:77953806652
SN - 0014-2999
VL - 640
SP - 68
EP - 74
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -