Effects of aripiprazole on MK-801-induced prepulse inhibition deficits and mitogen-activated protein kinase signal transduction pathway.
Based on NMDA hypofunction hypothesis for negative symptoms and cognitive deficits in schizophrenia, MK-801-induced animal models of schizophrenia may help us understand the different effects between typical and atypical antipsychotics. On the other hand, the mitogen-activated protein kinase (MAPK) signaling pathways may participate in antipsychotic actions. The aim of this study was to investigate the effects of aripiprazole on MK-801-induced prepulse inhibition (PPI) disruption and MAPK phosphorylation in mice. To clarify the effects of aripiprazole on MK-801-induced PPI disruption, we measured PPI of 51 ddY male mice after aripiprazole was administered 15 min prior to the injection of MK-801, and measured activation of cytosol and nuclear MAPK phosphorylation by western blotting. Aripiprazole (4.0 mg/kg) significantly reversed the MK-801 (0.15 mg/kg)-induced PPI deficits. Pretreatment of aripiprazole (40 mg/kg) had a tendency to suppress MK-801 (1.0 mg/kg)-induced pMEK/MEK (Ser218/222) activation. In addition, aripiprazole treatment showed a significant decrease of pERK/ERK. Our data suggested that aripiprazole may reverse MK-801-induced PPI deficits through regulation of MAPK phosphorylation in the same way as the atypical antipsychotic drug, clozapine.
Ishii
Daisuke
D
Department of Integrative Neurophysiology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan.
Matsuzawa
Daisuke
D
Kanahara
Nobuhisa
N
Matsuda
Shingo
S
Sutoh
Chihiro
C
Ohtsuka
Hiroyuki
H
Nakazawa
Ken
K
Kohno
Mami
M
Hashimoto
Kenji
K
Iyo
Masaomi
M
Shimizu
Eiji
E
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D013216:Reflex, Startle / Q000187:drug effects*; D015398:Signal Transduction
D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D016291:Dizocilpine Maleate; D000068180:Aripiprazole; D020928:Mitogen-Activated Protein Kinases