Cannabinoid CB1 receptor dependent effects of the NMDA antagonist phencyclidine in the social withdrawal model of schizophrenia

被引:32
作者
Haller, J
Szirmai, M
Varga, B
Ledent, C
Freund, TF
机构
[1] Hungarian Acad Sci, Inst Expt Med, Dept Behav Neurobiol, H-1450 Budapest, Hungary
[2] Univ Libre Bruxelles, IRIBHN, Brussels, Belgium
[3] Hungarian Acad Sci, Inst Expt Med, Dept Cellular & Network Neurobiol, Budapest, Hungary
来源
BEHAVIOURAL PHARMACOLOGY | 2005年 / 16卷 / 5-6期
关键词
cannabinoid; CB1; knockout phencyclidine; schizophrenia; social withdrawal; stereotypy; ataxia; mouse;
D O I
10.1097/00008877-200509000-00014
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Clinical and laboratory findings suggest that cannabinoid signalling is implicated in schizophrenia. However, the interaction remains poorly understood, as data are often contradictory. Here we investigated wild-type (WT) and cannabinoid CB1 receptor-knockout (CB1-KO) mice in the phencyclidine-induced social withdrawal model of schizophrenia. N-methyl-D-aspartate (NMDA) antagonists (including phencyclidine) induce psychotic symptoms in humans, and are used to model schizophrenia in a variety of experimental conditions. In WTs, 5 mg/kg phencyclidine increased locomotion and stereotyped behaviours, and decreased social interactions. These changes are consistent with a schizophrenia-like effect. In CB1-KOs, phencyclidine decreased locomotion, enhanced ataxia and stereotypy more markedly than in WTs, but did not affect social interactions. Locomotion showed a significant negative correlation with both ataxia and stereotypy, suggesting that in CB1-KOs, the locomotor suppressive effect of phencyclidine was secondary to changes in these variables. Our findings demonstrate that CB1 gene disruption dramatically alters the behavioural effects of the NNDA antagonist phencyclidine, suggesting that the CB1 receptor is involved in schizophrenia. As social disruption and stereotypy respectively are believed to model negative and positive symptoms of schizophrenia, our findings tentatively suggest that cannabinoids are differentially involved in these two symptom categories. These findings require verification by experiments involving CB1 receptor blockers, as the genetic and pharmacological blockade of receptors may not always provide similar results.
引用
收藏
页码:415 / 422
页数:8
相关论文
共 62 条
[31]   Schizophrenia and the cannabinoid receptor type 1 (CB1):: Association study using a single-base polymorphism in coding exon 1 [J].
Leroy, S ;
Griffon, N ;
Bourdel, MC ;
Olié, JP ;
Poirier, MF ;
Krebs, MO .
AMERICAN JOURNAL OF MEDICAL GENETICS, 2001, 105 (08) :749-752
[32]   Neuropharmacological profile of EMD 57445, a sigma receptor ligand with potential antipsychotic activity [J].
Maj, J ;
Rogoz, Z ;
Skuza, G ;
Mazela, H .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1996, 315 (03) :235-243
[33]  
MAKARA JK, 2004, SELECTIVE INHIBITION
[34]   EFFECTS OF PHENCYCLIDINE AND PHENCYCLIDINE BIOLOGS ON SENSORIMOTOR GATING IN THE RAT [J].
MANSBACH, RS ;
GEYER, MA .
NEUROPSYCHOPHARMACOLOGY, 1989, 2 (04) :299-308
[35]   SR141716A, a CB1 cannabinoid receptor antagonist, potentiates the locomotor stimulant effects of amphetamine and apomorphine [J].
Masserano, JM ;
Karoum, F ;
Wyatt, RJ .
BEHAVIOURAL PHARMACOLOGY, 1999, 10 (04) :429-432
[36]   Prefrontal cortex stimulation induces 2-arachidonoyl-glycerol-mediated suppression of excitation in dopamine neurons [J].
Melis, M ;
Perra, S ;
Muntoni, AL ;
Pillolla, G ;
Lutz, B ;
Marsicano, G ;
Di Marzo, V ;
Gessa, GL ;
Pistis, M .
JOURNAL OF NEUROSCIENCE, 2004, 24 (47) :10707-10715
[37]   Diagnostic and Statistical Manual of Mental Disorders [J].
Mittal, Vijay A. ;
Walker, Elaine F. .
PSYCHIATRY RESEARCH, 2011, 189 (01) :158-159
[38]   Mice with reduced NMDA receptor expression display behaviors related to schizophrenia [J].
Mohn, AR ;
Gainetdinov, RR ;
Caron, MG ;
Koller, BH .
CELL, 1999, 98 (04) :427-436
[39]   Behavioral sensitization to amphetamine follows chronic administration of the CB1 agonist WIN 55,212-2 in Lewis rats [J].
Muschamp, JW ;
Siviy, SM .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 2002, 73 (04) :835-842
[40]   CANNABIS AFFECTS THE SEVERITY OF SCHIZOPHRENIC SYMPTOMS - RESULTS OF A CLINICAL SURVEY [J].
NEGRETE, JC ;
KNAPP, WP ;
DOUGLAS, DE ;
SMITH, WB .
PSYCHOLOGICAL MEDICINE, 1986, 16 (03) :515-520