Inhibitory effects of aripiprazole on interferon-gamma-induced microglial activation via intracellular Ca2+ regulation in vitro.

Abstract:

:The activation of the inflammatory/immunological response system is suggested to be related to the pathophysiology of schizophrenia. Aripiprazole is a novel atypical antipsychotic, which is a high-affinity dopamine D(2) receptor partial agonist. Atypical antipsychotics, all of which have dopamine D(2) receptor antagonism, have recently reported to have significantly inhibitory effects on interferon (IFN)-gamma-induced microglial activation in vitro. In the present study, we investigated whether or not aripiprazole also has anti-inflammatory effect on IFN-gamma-induced microglial activation. Not quinpirole, dopamine D(2) full agonist, but aripiprazole significantly inhibited the generation of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha from IFN-gamma-activated microglia and suppressed the IFN-gamma-induced elevation of intracellular Ca(2+) concentrations ([Ca(2+)](i)) in murine microglial cells. Increased [Ca(2+)](i) has been reported to be required, but by itself not sufficient, for the release of NO and certain cytokines. As a result, we can speculate that aripiprazole may inhibit IFN-gamma-induced microglial activation through the suppression of IFN-gamma-induced elevation of [Ca(2+)](i) in microglia. Our results demonstrated that not only antipsychotics which have dopamine D(2) receptor antagonism but also aripiprazole have anti-inflammatory effects via the inhibition of microglial activation. Antipsychotics may therefore have a potentially useful therapeutic effect on patients with schizophrenia by reducing the microglial inflammatory reactions.

journal_name

J Neurochem

authors

Kato T,Mizoguchi Y,Monji A,Horikawa H,Suzuki SO,Seki Y,Iwaki T,Hashioka S,Kanba S

doi

10.1111/j.1471-4159.2008.05435.x

subject

Has Abstract

pub_date

2008-07-01 00:00:00

pages

815-25

issue

2

eissn

0022-3042

issn

1471-4159

pii

JNC5435

journal_volume

106

pub_type

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