Learning From Animal Models of Obsessive-Compulsive Disorder

被引:63
作者
Monteiro, Patricia [1 ,2 ,3 ]
Feng, Guoping [1 ,3 ]
机构
[1] MIT, Dept Brain & Cognit Sci, McGovern Inst Brain Res, Cambridge, MA 02139 USA
[2] Univ Coimbra, Ctr Neurosci & Cell Biol, Programme Expt Biol & Biomed, Coimbra, Portugal
[3] Eli & Edythe L Broad Inst & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA
基金
美国国家卫生研究院;
关键词
Animal models; Basal ganglia; CSTC; Obsessive-compulsive disorder; OCD; Striatum; Synapse; GENOME-WIDE ASSOCIATION; BASAL GANGLIA; GABAERGIC INTERNEURONS; PREFRONTAL CORTEX; 5-HT2C RECEPTORS; SYNAPTIC INPUT; SLC1A1; GENE; CIRCUITS; OCD; STRIATUM;
D O I
10.1016/j.biopsych.2015.04.020
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Obsessive-compulsive disorder (OCD) affects 2%-3% of the population worldwide and can cause significant distress and disability. Substantial challenges remain in the field of OCD research and therapeutics. Approved interventions alleviate symptoms only partially, with 30%-40% of patients being resistant to treatment. Although the etiology of OCD is still unknown, research evidence points toward the involvement of cortico-striato-thalamocortical circuitry. This review focuses on the most recent behavioral, genetics, and neurophysiologic findings from animal models of OCD. Based on evidence from these models and parallels with human studies, we discuss the circuit hyperactivity hypothesis for OCD, a potential circuitry dysfunction of action termination, and the involvement of candidate genes. Adding a more biologically valid framework to OCD will help researchers define and test new hypotheses and facilitate the development of targeted therapies based on disease-specific mechanisms.
引用
收藏
页码:7 / 16
页数:10
相关论文
共 108 条
[1]   Impact of Serotonin 2C Receptor Null Mutation on Physiology and Behavior Associated with Nigrostriatal Dopamine Pathway Function [J].
Abdallah, Luna ;
Bonasera, Stephen J. ;
Hopf, F. Woodward ;
O'Dell, Laura ;
Giorgetti, Marco ;
Jongsma, Minke ;
Carra, Scott ;
Pierucci, Massimo ;
Di Giovanni, Giuseppe ;
Esposito, Ennio ;
Parsons, Loren H. ;
Bonci, Antonello ;
Tecott, Laurence H. .
JOURNAL OF NEUROSCIENCE, 2009, 29 (25) :8156-8165
[2]   Sequence variants in SLITRK1 are associated with Tourette's syndrome [J].
Abelson, JF ;
Kwan, KY ;
O'Roak, BJ ;
Baek, DY ;
Stillman, AA ;
Morgan, TM ;
Mathews, CA ;
Pauls, DA ;
Rasin, MR ;
Gunel, M ;
Davis, NR ;
Ercan-Sencicek, AG ;
Guez, DH ;
Spertus, JA ;
Leckman, JF ;
Dure, LS ;
Kurlan, R ;
Singer, HS ;
Gilbert, DL ;
Farhi, A ;
Louvi, A ;
Lifton, RP ;
Sestan, N ;
State, MW .
SCIENCE, 2005, 310 (5746) :317-320
[3]   Microglia: Scapegoat, Saboteur, or Something Else? [J].
Aguzzi, Adriano ;
Barres, Ben A. ;
Bennett, Mariko L. .
SCIENCE, 2013, 339 (6116) :156-161
[4]   Repeated Cortico-Striatal Stimulation Generates Persistent OCD-Like Behavior [J].
Ahmari, Susanne E. ;
Spellman, Timothy ;
Douglass, Neria L. ;
Kheirbek, Mazen A. ;
Simpson, H. Blair ;
Deisseroth, Karl ;
Gordon, Joshua A. ;
Hen, Rene .
SCIENCE, 2013, 340 (6137) :1234-1239
[5]   THE FUNCTIONAL-ANATOMY OF BASAL GANGLIA DISORDERS [J].
ALBIN, RL ;
YOUNG, AB ;
PENNEY, JB .
TRENDS IN NEUROSCIENCES, 1989, 12 (10) :366-375
[6]  
Aldridge JW, 1998, J NEUROSCI, V18, P2777
[7]   FUNCTIONAL ARCHITECTURE OF BASAL GANGLIA CIRCUITS - NEURAL SUBSTRATES OF PARALLEL PROCESSING [J].
ALEXANDER, GE ;
CRUTCHER, MD .
TRENDS IN NEUROSCIENCES, 1990, 13 (07) :266-271
[8]   PARALLEL ORGANIZATION OF FUNCTIONALLY SEGREGATED CIRCUITS LINKING BASAL GANGLIA AND CORTEX [J].
ALEXANDER, GE ;
DELONG, MR ;
STRICK, PL .
ANNUAL REVIEW OF NEUROSCIENCE, 1986, 9 :357-381
[9]   Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse [J].
Aoyama, K ;
Suh, SW ;
Hamby, AM ;
Liu, JL ;
Chan, WY ;
Chen, YM ;
Swanson, RA .
NATURE NEUROSCIENCE, 2006, 9 (01) :119-126
[10]   Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder [J].
Arnold, Paul Daniel ;
Sicard, Tricia ;
Burroughs, Eliza ;
Richter, Margaret A. ;
Kennedy, James L. .
ARCHIVES OF GENERAL PSYCHIATRY, 2006, 63 (07) :769-776