Olanzapine and risperidone block a high dose of methamphetamine-induced schizophrenia-like behavioral abnormalities and accompanied apoptosis in the medial prefrontal cortex

被引:49
作者
Abekawa, Tomohiro [1 ]
Ito, Koki [1 ]
Nakagawa, Shin [1 ]
Nakato, Yasuya [1 ]
Koyama, Tsukasa [1 ]
机构
[1] Hokkaido Univ, Grad Sch Med, Dept Psychiat, Sapporo, Hokkaido 0608638, Japan
关键词
olanzapine; risperidone; apoptosis; PPI; methamphetamine; schizophrenia;
D O I
10.1016/j.schres.2007.12.488
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
This study aims to propose a comprehensive new model for schizophrenia, which shows PPI disruption at baseline state as an endophenotype, the development of cross-sensitization to an NMDA receptor antagonist, MK-801 as a clinical phenotype of the progression into treatment-resistance, and accompanied induction of apoptosis in the medial prefrontal cortex as a critical possibility during the progression. Repeated administration of a high dose of methamphetamine (METH) (2.5 mg/kg), which could increase glutamate levels in the medial prefrontal cortex (mPFC), induced TUNEL-positive cells in this region, accompanied development of behavioral cross-sensitization to MK-801 in response to a challenge injection of MK-801, and PPI disruption at baseline state without a challenge injection. Olanzapine (OLZ) (1.0 mg/kg) and risperidone (RIS) (0.1 mg/kg), which inhibited and remarkably attenuated METH (2.5 mg/kg)-induced increases in glutamate levels, respectively, blocked not only the induction of TUNEL-positive cells in the mPFC but also the accompanied development of above behavioral abnormalities. These findings suggest that repeating the METH-induced glutamate release produces behavioral abnormalities as a clinical phenotype of schizophrenia, accompanied apoptosis as a critical possibility during the progression, and suggest that sufficient dose of olanzapine and risperidone can block the development of these behavioral abnormalities and accompanied apoptosis during the progression. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:84 / 94
页数:11
相关论文
共 46 条
[1]   Role of the simultaneous enhancement of NMDA and dopamine D1 receptor-mediated neurotransmission in the effects of clozapine on phencyclidine-induced acute increases in glutamate levels in the rat medial prefrontal cortex [J].
Abekawa, T. ;
Ito, K. ;
Koyama, T. .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2006, 374 (03) :177-193
[2]   Effects of NRA0045, a novel potent antagonist at dopamine D4, 5-HT2A, and α1 adrenaline receptors, and NRA0160, a selective D4 receptor antagonist, on phencyclidine-induced behavior and glutamate release in rats [J].
Abekawa, T ;
Honda, M ;
Ito, K ;
Koyama, T .
PSYCHOPHARMACOLOGY, 2003, 169 (3-4) :247-256
[3]   D1 dopamine receptor activation reduces extracellular glutamate and GABA concentrations in the medial prefrontal cortex [J].
Abekawa, T ;
Ohmori, T ;
Ito, K ;
Koyama, T .
BRAIN RESEARCH, 2000, 867 (1-2) :250-254
[4]  
Arvanov VL, 1997, J PHARMACOL EXP THER, V283, P226
[5]  
Bakshi VP, 1998, J NEUROSCI, V18, P8394
[6]  
BAKSHI VP, 1994, J PHARMACOL EXP THER, V271, P787
[7]   DNA fragmentation decreased in schizophrenia but not bipolar disorder [J].
Benes, FM ;
Walsh, J ;
Bhattacharyya, S ;
Sheth, A ;
Berretta, S .
ARCHIVES OF GENERAL PSYCHIATRY, 2003, 60 (04) :359-364
[8]   Impact of prepulse characteristics on the detection of sensorimotor gating deficits in schizophrenia [J].
Braff, DL ;
Geyer, MA ;
Light, GA ;
Sprock, J ;
Perry, W ;
Cadenhead, KS ;
Swerdlow, NR .
SCHIZOPHRENIA RESEARCH, 2001, 49 (1-2) :171-178
[9]   The effect of zotepine, risperidone, clozapine and olanzapine on MK-801-disrupted sensorimotor gating [J].
Bubeníková, V ;
Votava, M ;
Horácek, J ;
Pálenícek, T ;
Dockery, C .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 2005, 80 (04) :591-596
[10]   DNA fragmentation is increased in non-GABAergic neurons in bipolar disorder but not in schizophrenia [J].
Buttner, Ned ;
Bhattacharyya, Sujoy ;
Walsh, John ;
Benes, Francine M. .
SCHIZOPHRENIA RESEARCH, 2007, 93 (1-3) :33-41