Effects of phencyclidine (PCP) and MK 801 on the EEGq in the prefrontal cortex of conscious rats;: antagonism by clozapine, and antagonists of AMPA-, α1- and 5-HT2A-receptors

被引:50
作者
Sebban, C
Tesolin-Decros, B
Ciprian-Ollivier, J
Perret, L
Spedding, M
机构
[1] Inst Rech Int Servier, F-92200 Neuilly Sur Seine, France
[2] Hop Charles Foix, Lab Biol Vieillissment, F-94205 Ivry, France
[3] Univ Buenos Aires, Moyana Hosp, Acad Unit, RA-1425 Buenos Aires, DF, Argentina
关键词
prefrontal cortex; phencyclidine (PCP); clozapine; AMPA; GYKI; 52466; 5-HT(2A)-receptors; M100907; EEG; schizophrenia;
D O I
10.1038/sj.bjp.0704451
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The electroencephalographic (EEG) effects of the propsychotic agent phencyclidine (PCP), were studied in conscious rats using power spectra (0-30 Hz), from the prefrontal cortex or sensorimotor cortex. PCP (0.1-3 mg kg(-) s.c.) caused a marked dose-dependent increase in EEG power in the frontal cortex at 1-3 Hz with decreases in power at higher frequencies (9-30 Hz). At high doses (3 mg kg(-1) s.c.) the entire spectrum shifted to more positive values, indicating an increase in cortical synchronization. MK 801 (0.05-0.1 mg kg(-1) i.p.) caused similar effects but with lesser changes in power. 2 In contrast, the non-competitive AMPA antagonists GYKI 52466 and GYKI 53655 increased EEG power over the whole power spectrum (1-10 mg kg(-1) i.p.). The atypical antipsychotic clozapine (0.2 mg kg(-1) s.c.) synchronized the EEG (peak 8 Hz). The 5-HT(2A)-antagonist, M100907, specifically increased EEG power at 2-3 Hz at low doses (10 and 50 mug kg(-1) s.c.), whereas at higher doses (0.1 mg kg(-1) s.c.) the profile resembled that of clozapine. 3 Clozapine (0.2 mg kg(-1) s.c.), GYKI 53655 (5 mg kg(-1) i.p.), prazosin (0.05 and 0.1 mg kg(-1) i.p.), and M100907 (0.01 and 0.05 mg kg(-1) s.c.) antagonized the decrease in power between 5 and 30 Hz caused by PCP (1 mg kg(-1) s.c.), but not the increase in power at 1-3 Hz in prefrontal cortex.
引用
收藏
页码:65 / 78
页数:14
相关论文
共 103 条
[1]   The NMDA antagonist model for schizophrenia: Promise and pitfalls [J].
Abi-Saab, WM ;
D'Souza, DC ;
Moghaddam, B ;
Krystal, JH .
PHARMACOPSYCHIATRY, 1998, 31 :104-109
[2]   Corticolimbic dopamine neurotransmission is temporally dissociated from the cognitive and locomotor effects of phencyclidine [J].
Adams, B ;
Moghaddam, B .
JOURNAL OF NEUROSCIENCE, 1998, 18 (14) :5545-5554
[3]  
Aghajanian G. K., 1998, Society for Neuroscience Abstracts, V24, P1366
[4]   Serotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate release [J].
Aghajanian, GK ;
Marek, GJ .
BRAIN RESEARCH, 1999, 825 (1-2) :161-171
[5]   Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells [J].
Aghajanian, GK ;
Marek, GJ .
NEUROPHARMACOLOGY, 1997, 36 (4-5) :589-599
[6]   Serotonin model of schizophrenia: emerging role of glutamate mechanisms [J].
Aghajanian, GK ;
Marek, GJ .
BRAIN RESEARCH REVIEWS, 2000, 31 (2-3) :302-312
[7]  
ALLEN RM, 1978, AM J PSYCHIAT, V135, P1081
[8]   Evidence for association between polymorphisms in the promoter and coding regions of the 5-HT2A receptor gene and response to clozapine [J].
Arranz, MJ ;
Munro, J ;
Owen, MJ ;
Spurlock, G ;
Sham, PC ;
Zhao, J ;
Kirov, G ;
Collier, DA ;
Kerwin, RW .
MOLECULAR PSYCHIATRY, 1998, 3 (01) :61-66
[9]  
ARRANZ MJ, 1996, NEUROSCI LETT, V217, P2
[10]   ANTAGONISM OF PHENCYCLIDINE-INDUCED DEFICITS IN PREPULSE INHIBITION BY THE PUTATIVE ATYPICAL ANTIPSYCHOTIC OLANZAPINE [J].
BAKSHI, VP ;
GEYER, MA .
PSYCHOPHARMACOLOGY, 1995, 122 (02) :198-201