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Animal models of obsessive-compulsive spectrum disorders

Published online by Cambridge University Press:  02 October 2013

Laure-Sophie Camilla d'Angelo ,
Dawn M. Eagle ,
Jon E. Grant ,
Naomi A. Fineberg ,
Trevor W. Robbins  and
Samuel R. Chamberlain
Laure-Sophie Camilla d'Angelo*
Affiliation:
Departments of Psychology & Psychiatry, and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom
Dawn M. Eagle
Affiliation:
Departments of Psychology & Psychiatry, and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom
Jon E. Grant
Affiliation:
Department of Psychiatry, University of Chicago, Chicago, Illinois, USA
Naomi A. Fineberg
Affiliation:
National Treatment Service for England & Wales, Welwyn Garden City, Herfordshire, United Kingdom Department of Psychiatry, University of Hertfordshire, Herfordshire, United Kingdom
Trevor W. Robbins
Affiliation:
Departments of Psychology & Psychiatry, and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom
Samuel R. Chamberlain*
Affiliation:
Departments of Psychology & Psychiatry, and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom Cambridge and Peterborough NHS Foundation Trust (CPFT), Cambridge, United Kingdom
*
*Addresses for correspondence: Ms. Laure-Sophie d'Angelo, Department of Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB; (Email [email protected];)
Dr. Samuel Chamberlain, Level E4, Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB0 0QQ, UK. ([email protected])
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Abstract

Obsessive-compulsive disorder (OCD) and related conditions (trichotillomania, pathological skin-picking, pathological nail-biting) are common and disabling. Current treatment approaches fail to help a significant proportion of patients. Multiple tiers of evidence link these conditions with underlying dysregulation of particular cortico-subcortical circuitry and monoamine systems, which represent targets for treatment. Animal models designed to capture aspects of these conditions are critical for several reasons. First, they help in furthering our understanding of neuroanatomical and neurochemical underpinnings of the obsessive-compulsive (OC) spectrum. Second, they help to account for the brain mechanisms by which existing treatments (pharmacotherapy, psychotherapy, deep brain stimulation) exert their beneficial effects on patients. Third, they inform the search for novel treatments. This article provides a critique of key animal models for selected OC spectrum disorders, beginning with initial work relating to anxiety, but moving on to recent developments in domains of genetic, pharmacological, cognitive, and ethological models. We find that there is a burgeoning literature in these areas with important ramifications, which are considered, along with salient future lines of research.

Keywords

CognitionCompulsivityDopamineGamblingImpulsivityObsessive-compulsivePrefrontal cortexSerotoninSpectrumStriatumTrichotillomania
Type
Review Articles
Information
CNS Spectrums , Volume 19 , Issue 1 , February 2014 , pp. 28 - 49
Copyright
Copyright © Cambridge University Press 2013 

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Footnotes

The authors thank the ECNP Research Network Initiative Obsessive Compulsive and Related Disorders Research Network.

References

1. Fontenelle, LF, Mendlowicz, MV, Versiani, M. The descriptive epidemiology of obsessive-compulsive disorder. Prog Neuropsychopharmacol Biolog Psychiatry. 2006; 30(3): 327–337.CrossRefGoogle ScholarPubMed
2. Zohar, AH. The epidemiology of obsessive-compulsive disorder in children and adolescents. Child Adolesc Psychiatr Clin N Am. 1999; 8(3): 445–460.CrossRefGoogle ScholarPubMed
3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Version IV-TR. Arlington, VA: American Psychiatric Association; 2000.Google Scholar
4. Hollander, E. Obsessive-compulsive spectrum phenomena and the DSM-V developmental process. CNS Spectr. 2008; 13(2): 107–108.CrossRefGoogle ScholarPubMed
5. Hollander, E, Wong, CM. Obsessive-compulsive spectrum disorders. J Clin Psychiatry. 1995; 56(suppl 4): 3–6; discussion 53–55.Google Scholar
6. Phillips, KA. The obsessive-compulsive spectrums. Psychiatr Clin North Am. 2002; 25(4): 791–809.Google Scholar
7. Stein, DJ, Hollander, E. Obsessive-compulsive spectrum disorders. J Clin Psychiatry. 1995; 56(6): 265–266.Google Scholar
8. Swedo, SE, Leonard, HL. Trichotillomania: an obsessive compulsive spectrum disorder? Psychiatr Clin North Am. 1992; 15(4): 777–790.CrossRefGoogle ScholarPubMed
9. Bienvenu, OJ, Samuels, JF, Riddle, MA, etal. The relationship of obsessive-compulsive disorder to possible spectrum disorders: results from a family study. Biol Psychiatry. 2000; 48(4): 287–293.Google Scholar
10. Fineberg, NA, Gale, TM. Evidence-based pharmacotherapy of obsessive compulsive disorder. Int J Neuropsychopharmacol. 2005; 8(1): 107–129.Google Scholar
11. Chamberlain, SR, Odlaug, BL, Boulougouris, V, Fineberg, NA, Grant, JE. Trichotillomania: neurobiology and treatment. Neurosci Biobehav Rev. 2009; 33(6): 831–842.CrossRefGoogle ScholarPubMed
12. Solomon, RL, Kamin, LJ, Wynne, LC. Traumatic avoidance learning: the outcomes of several extinction procedures with dogs. J Abnorm Psychol. 1953; 48(2): 291–302.Google Scholar
13. Meyer, V. Modification of expectations in cases with obsessional rituals. Behav Res Ther. 1966; 4(4): 273–280.Google Scholar
14. Chamberlain, SR, Blackwell, AD, Fineberg, N, Robbins, TW, Sahakian, BJ. The neuropsychology of obsessive compulsive disorder: the importance of failures in cognitive and behavioural inhibition as candidate endophenotypic markers. Neurosci Biobehav Rev. 2005; 29(3): 399–419.CrossRefGoogle ScholarPubMed
15. Menzies, L, Chamberlain, SR, Laird, AR, etal. Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited. Neurosci Biobehav Rev. 2008; 32(3): 525–549.Google Scholar
16. Stein, DJ, Chamberlain, SR, Fineberg, N. An A-B-C model of habit disorders: hair-pulling, skin-picking, and other stereotypic conditions. CNS Spectr. 2006; 11(11): 824–827.Google Scholar
17. Nestler, EJ, Hyman, SE. Animal models of neuropsychiatric disorders. Nat Neurosci. 2010; 13: 1161–1169.CrossRefGoogle ScholarPubMed
18. McKinney, WT Jr, Bunney, WE Jr. Animal model of depression. I. Review of evidence: implications for research. Arch Gen Psychiatry. 1969; 21(2): 240–248.Google Scholar
19. Matthysse, S. Animal models in psychiatric research. Prog Brain Res. 1986; 65: 259–270.CrossRefGoogle ScholarPubMed
20. Geyer, MA, Markou, A. Animal models of psychiatric disorders. In Bloom FE, Kupfer DJ, eds. Psychopharmacology: The Fourth Generation of Progress. New York: Raven Press; 1995: 787–798.Google Scholar
21. Geyer, MA, Markou, A. The role of preclinical models in the development of psychotropic drugs. In: Davis KL, Coyle JT, Nemeroff C, eds. Neuropsychopharmacology: The Fifth Generation of Progress. Lippincott, Williams, & Wilkins; Philadelphia, PA, 2002: 445–455.Google Scholar
22. Willner, P. The validity of animal models of depression. Psychopharmacology. 1984; 83(1): 1–16.CrossRefGoogle ScholarPubMed
23. Willner, P. Validation criteria for animal models of human mental disorders: learned helplessness as a paradigm case. Prog Neuropsychopharmacol Biol Psychiatry. 1986; 10: 677–690.Google Scholar
24. Pigott, TA, Seay, SM. A review of the efficacy of selective serotonin reuptake inhibitors in obsessive-compulsive disorder. J Clin Psychiatry. 1999; 60(2): 101–106.Google Scholar
25. Hettema, JM, Neale, MC, Kendler, KS. A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry. 2001; 158(10): 1568–1578.Google Scholar
26. Jonnal, AH, Gardner, CO, Prescott, CA, Kendler, KS. Obsessive and compulsive symptoms in a general population sample of female twins. Am J Med Genet. 2000; 96(6): 791–796.3.0.CO;2-C>CrossRefGoogle Scholar
27. Wang, L, Simpson, HB, Dulawa, SC. Assessing the validity of current mouse genetic models of obsessive-compulsive disorder. Behav Pharmacol. 2009; 20: 119–133.CrossRefGoogle ScholarPubMed
28. Novak, CE, Keuthen, NJ, Stewart, SE, Pauls, DL. A twin concordance study of trichotillomania. Am J Med Genet B Neuropsychiatr Genet. 2009; 150B(7): 944–949.Google Scholar
29. Joel, D. Current animal models of obsessive compulsive disorder: a critical review. Prog Neuropsychopharmacol Biol Psychiatry. 2006; 30(3): 374–388.CrossRefGoogle ScholarPubMed
30. Boulougouris, V, Chamberlain, SR, Robbins, TW. Cross-species models of OCD spectrum disorders. Psychiatry Res. 2009; 170(1): 15–21.CrossRefGoogle ScholarPubMed
31. Greer, JM, Capecchi, MR. Hoxb8 is required for normal grooming behavior in mice. Neuron. 2002; 33(1): 23–34.Google Scholar
32. Campbell, KM, de Lecea, L, Severynse, DM, etal. OCD-Like behaviors caused by a neuropotentiating transgene targeted to cortical and limbic D1+ neurons. J Neurosci. 1999; 19(12): 5044–5053.CrossRefGoogle ScholarPubMed
33. Campbell, KM, McGrath, MJ, Burton, FH. Behavioral effects of cocaine on a transgenic mouse model of cortical-limbic compulsion. Brain Res. 1999; 833(2): 216–224.Google Scholar
34. Campbell, KM, McGrath, MJ, Burton, FH. Differential response of cortical-limbic neuropotentiated compulsive mice to dopamine D1 and D2 receptor antagonists. Eur J Pharmacol. 1999; 371(2–3): 103–111.Google Scholar
35. McGrath, MJ, Campbell, KM, Burton, FH. The role of cognitive and affective processing in a transgenic mouse model of cortical-limbic neuropotentiated compulsive behavior. Behav Neurosci. 1999; 113: 1249–1256.Google Scholar
36. McGrath, MJ, Campbell, KM, Veldman, MB, Burton, FH. Anxiety in a transgenic mouse model of cortical-limbic neuro-potentiated compulsive behavior. Behav Pharmacol. 1999; 10(5): 435–443.CrossRefGoogle Scholar
37. Nordstrom, EJ, Burton, FH. A transgenic model of comorbid Tourette's syndrome and obsessive-compulsive disorder circuitry. Mol Psychiatry. 2002; 7(6): 617–625, 524.CrossRefGoogle ScholarPubMed
38. Berridge, KC, Aldridge, JW, Houchard, KR, Zhuang, X. Sequential super-stereotypy of an instinctive fixed action pattern in hyper-dopaminergic mutant mice: a model of obsessive compulsive disorder and Tourette's. BMC Biol. 2005; 3: 4.CrossRefGoogle Scholar
39. Chou-Green, JM, Holscher, TD, Dallman, MF, Akana, SF. Compulsive behavior in the 5-HT2C receptor knockout mouse. Physiol Behav. 2003; 78(4–5): 641–649.CrossRefGoogle ScholarPubMed
40. Young, JW, van Enkhuizen, J, Winstanley, CA, Geyer, MA. Increased risk-taking behavior in dopamine transporter knockdown mice: further support for a mouse model of mania. J Psychopharmacol. 2011; 25: 934–943.Google Scholar
41. Zhuang, X, Oosting, RS, Jones, SR, etal. Hyperactivity and impaired response habituation in hyperdopaminergic mice. Proc Natl Acad Sci U S A. 2001; 98(4): 1982–1987.Google Scholar
42. Tecott, LH, Sun, LM, Akana, SF, etal. Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature. 1995; 374: 542–546.Google Scholar
43. Nonogaki, K, Strack, AM, Dallman, MF, Tecott, LH. Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat Med. 1998; 4: 1152–1156.CrossRefGoogle ScholarPubMed
44. Vickers, SP, Clifton, PG, Dourish, CT, Tecott, LH. Reduced satiating effect of d-fenfluramine in serotonin 5-HT(2C) receptor mutant mice. Psychopharmacology. 1999; 143: 309–314.Google Scholar
45. Tecott, LH, Logue, SF, Wehner, JM, Kauer, JA. Perturbed dentate gyrus function in serotonin 5-HT2C receptor mutant mice. Proc Natl Acad Sci U S A. 1998; 95: 15026–15031.Google Scholar
46. Heisler, LK, Zhou, L, Bajwa, P, Hsu, J, Tecott, LH. Serotonin 5-HT(2C) receptors regulate anxiety-like behavior. Genes Brain Behav. 2007; 6: 491–496.Google Scholar
47. Rocha, BA, Goulding, EH, O'Dell, LE, etal. Enhanced locomotor, reinforcing, and neurochemical effects of cocaine in serotonin 5-hydroxytryptamine 2C receptor mutant mice. J Neurosci. 2002; 22: 10039–10045.Google Scholar
48. Tsaltas, E, Kontis, D, Chrysikakou, S, etal. Reinforced spatial alternation as an animal model of obsessive-compulsive disorder (OCD): investigation of 5-HT2C and 5-HT1D receptor involvement in OCD pathophysiology. Biol Psychiatry. 2005; 57(10): 1176–1185.Google Scholar
49. Boulougouris, V, Glennon, JC, Robbins, TW. Dissociable effects of selective 5-HT2A and 5-HT2C receptor antagonists on serial spatial reversal learning in rats. Neuropsychopharmacology. 2008; 33(8): 2007–2019.Google Scholar
50. Welch, JM, Wang, D, Feng, G. Differential mRNA expression and protein localization of the SAP90/PSD-95-associated proteins (SAPAPs) in the nervous system of the mouse. J Comp Neurol. 2004; 472: 24–39.Google Scholar
51. Chamberlain, SR, Menzies, LA, Fineberg, NA, etal. Grey matter abnormalities in trichotillomania: morphometric magnetic resonance imaging study. Br J Psychiatry. 2008; 193(3): 216–221.Google Scholar
52. Fineberg, NA, Potenza, MN, Chamberlain, SR, etal. Probing compulsive and impulsive behaviors, from animal models to endophenotypes: a narrative review. Neuropsychopharmacology. 2010; 35(3): 591–604.Google Scholar
53. Welch, JM, Lu, J, Rodriguiz, RM, etal. Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice. Nature. 2007; 448(7156): 894–900.CrossRefGoogle ScholarPubMed
54. Bienvenu, OJ, Wang, Y, Shugart, YY, etal. Sapap3 and pathological grooming in humans: results from the OCD collaborative genetics study. Am J Med Genet B Neuropsychiatr Genet. 2009; 150B(5): 710–720.Google Scholar
55. Zuchner, S, Wendland, JR, Ashley-Koch, AE, etal. Multiple rare SAPAP3 missense variants in trichotillomania and OCD. Mol Psychiatry. 2009; 14: 6–9.Google Scholar
56. Aruga, J, Mikoshiba, K. Identification and characterization of Slitrk, a novel neuronal transmembrane protein family controlling neurite outgrowth. Mol Cell Neurosci. 2003; 24: 117–129.CrossRefGoogle ScholarPubMed
57. Aruga, J, Yokota, N, Mikoshiba, K. Human SLITRK family genes: genomic organization and expression profiling in normal brain and brain tumor tissue. Gene. 2003; 315: 87–94.CrossRefGoogle ScholarPubMed
58. Shmelkov, SV, Hormigo, A, Jing, D, etal. Slitrk5 deficiency impairs corticostriatal circuitry and leads to obsessive-compulsive-like behaviors in mice. Nat Med. 2010; 16(5): 598–602.Google Scholar
59. Fisher, CR, Graves, KH, Parlow, AF, Simpson, ER. Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cyp19 gene. Proc Natl Acad Sci U S A. 1998; 95: 6965–6970.CrossRefGoogle ScholarPubMed
60. Hill, RA, McInnes, KJ, Gong, ECH, etal. Estrogen deficient male mice develop compulsive behavior. Biol Psychiatry. 2007; 61: 359–366.Google Scholar
61. Karayiorgou, M, Altemus, M, Galke, BL, etal. Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder. Proc Natl Acad Sci U S A. 1997; 94(9): 4572–4575.Google Scholar
62. Pooley, EC, Fineberg, N, Harrison, PJ. The met(158) allele of catechol-O-methyltransferase (COMT) is associated with obsessive-compulsive disorder in men: case-control study and meta-analysis. Mol Psychiatry. 2007; 12(6): 556–561.Google Scholar
63. Kumari, V, Kaviani, H, Raven, PW, Gray, JA, Checkley, SA. Enhanced startle reactions to acoustic stimuli in patients with obsessive-compulsive disorder. Am J Psychiatry. 2001; 158: 134–136.CrossRefGoogle ScholarPubMed
64. van den Buuse, M, Simpson, ER, Jones, ME. Prepulse inhibition of acoustic startle in aromatase knock-out mice: effects of age and gender. Genes Brain Behav. 2003; 2(2): 93–102.Google Scholar
65. Lochner, C, Hemmings, SM, Kinnear, CJ, etal. Gender in obsessive-compulsive disorder: clinical and genetic findings. Eur Neuropsychopharmacol. 2004; 14(2): 105–113.CrossRefGoogle ScholarPubMed
66. Yadin, E, Friedman, E, Bridger, WH. Spontaneous alternation behavior: an animal model for obsessive-compulsive disorder? Pharmacol Biochem Behav. 1991; 40(2): 311–315.CrossRefGoogle ScholarPubMed
67. Fernandez-Guasti, A, Ulloa, RE, Nicolini, H. Age differences in the sensitivity to clomipramine in an animal model of obsessive-compulsive disorder. Psychopharmacology. 2003; 166: 195–201.Google Scholar
68. Hollander, E, DeCaria, C, Gully, R, etal. Effects of chronic fluoxetine treatment on behavioral and neuroendocrine responses to meta-chlorophenylpiperazine in obsessive-compulsive disorder. Psychiatry Res. 1991; 36(1): 1–17.Google Scholar
69. Zohar, J, Insel, TR, Zohar-Kadouch, RC, Hill, JL, Murphy, DL. Serotonergic responsivity in obsessive-compulsive disorder: effects of chronic clomipramine treatment. Arch Gen Psychiatry. 1988; 45(2): 167–172.CrossRefGoogle ScholarPubMed
70. Papakosta, VM, Kalogerakou, S, Kontis, D, etal. 5-HT2C receptor involvement in the control of persistence in the reinforced spatial alternation animal model of obsessive-compulsive disorder. Behav Brain Res. 2013; 243: 176–183.Google Scholar
71. Graf, M. 5-HT2c receptor activation induces grooming behaviour in rats: possible correlations with obsessive-compulsive disorder. Neuropsychopharmacol Hung. 2006; 8(1): 23–28.Google ScholarPubMed
72. Fernandez-Guasti, A, Agrati, D, Reyes, R, Ferreira, A. Ovarian steroids counteract serotonergic drugs actions in an animal model of obsessive-compulsive disorder. Psychoneuroendocrinology. 2006; 31: 924–934.Google Scholar
73. Umathe, SN, Vaghasiya, JM, Jain, NS, Dixit, PV. Neurosteroids modulate compulsive and persistent behavior in rodents: implications for obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2009; 33(7): 1161–1166.Google Scholar
74. Ulloa, R-E, Nicolini, H, Fernandez-Guasti, A. Sex differences on spontaneous alternation in prepubertal rats: implications for an animal model of obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2004; 28: 687–692.Google Scholar
75. Bigos, KL, Folan, MM, Jones, MR, etal. Dysregulation of neurosteroids in obsessive compulsive disorder. J Psychiatr Res. 2009; 43: 442–445.Google Scholar
76. Andrade, P, Fernandez-Guasti, A, Carrillo-Ruiz, JD, etal. Effects of bilateral lesions in thalamic reticular nucleus and orbitofrontal cortex in a T-maze perseverative model produced by 8-OH-DPAT in rats. Behav Brain Res. 2009; 203: 108–112.CrossRefGoogle Scholar
77. Jimenez-Ponce, F, Velasco-Campos, F, Castro-Farfan, G, etal. Preliminary study in patients with obsessive-compulsive disorder treated with electrical stimulation in the inferior thalamic peduncle. Neurosurgery. 2009; 65(6 suppl): 203–209; discussion 209.Google ScholarPubMed
78. Szechtman, H, Sulis, W, Eilam, D. Quinpirole induces compulsive checking behavior in rats: a potential animal model of obsessive-compulsive disorder (OCD). Behav Neurosci. 1998; 112(6): 1475–1485.Google Scholar
79. Cioli, I, Caricati, A, Nencini, P. Quinpirole- and amphetamine-induced hyperdipsia: influence of fluid palatability and behavioral cost. Behav Brain Res. 2000; 109: 9–18.Google Scholar
80. Milella, MS, Amato, D, Badiani, A, Nencini, P. The influence of cost manipulation on water contrafreeloading induced by repeated exposure to quinpirole in the rat. Psychopharmacology. 2008; 197: 379–390.Google Scholar
81. Szechtman, H, Woody, E. Obsessive-compulsive disorder as a disturbance of security motivation. Psychol Rev. 2004; 111(1): 111–127.Google Scholar
82. De Carolis, L, Schepisi, C, Milella, MS, Nencini, P. Clomipramine, but not haloperidol or aripiprazole, inhibits quinpirole-induced water contrafreeloading, a putative animal model of compulsive behavior. Psychopharmacology. 2011; 218: 749–759.CrossRefGoogle ScholarPubMed
83. Mundt, A, Klein, J, Joel, D, etal. High-frequency stimulation of the nucleus accumbens core and shell reduces quinpirole-induced compulsive checking in rats. Eur J Neurosci. 2009; 29(12): 2401–2412.CrossRefGoogle ScholarPubMed
84. Winter, C, Mundt, A, Jalali, R, etal. High frequency stimulation and temporary inactivation of the subthalamic nucleus reduce quinpirole-induced compulsive checking behavior in rats. Exp Neur. 2008; 210(1): 217–228.Google Scholar
85. Dvorkin, A, Silva, C, McMurran, T, etal. Features of compulsive checking behavior mediated by nucleus accumbens and orbital frontal cortex. Eur J Neurosci. 2010; 32(9): 1552–1563.Google Scholar
86. Alkhatib, AH, Dvorkin-Gheva, A, Szechtman, H. Quinpirole and 8-OH-DPAT induce compulsive checking behavior in male rats by acting on different functional parts of an OCD neurocircuit. Behav Pharmacol. 2013; 24: 65–73.Google Scholar
87. Andersen, SL, Greene-Colozzi, EA, Sonntag, KC. A novel, multiple symptom model of obsessive-compulsive-like behaviors in animals. Biol Psychiatry. 2010; 68: 741–747.Google Scholar
88. Chamberlain, SR, Menzies, L, Hampshire, A, etal. Orbitofrontal dysfunction in patients with obsessive-compulsive disorder and their unaffected relatives. Science. 2008; 321(5887): 421–422.Google Scholar
89. Moritz, S, Hottenrott, B, Randjbar, S, etal. Perseveration and not strategic deficits underlie delayed alternation impairment in obsessive-compulsive disorder (OCD). Psychiatry Res. 2009; 170: 66–69.Google Scholar
90. Jaafari, N, Frasca, M, Rigalleau, F, etal. Forgetting what you have checked: a link between working memory impairment and checking behaviors in obsessive-compulsive disorder. Eur Psychiatry. 2013; 28: 87–93.Google Scholar
91. Andersen, SL. Stimulants and the developing brain. Trends Pharmacol Sci. 2005; 26(5): 237–243.CrossRefGoogle ScholarPubMed
92. Shanahan, NA, Holick Pierz, KA, Masten, VL, etal. Chronic reductions in serotonin transporter function prevent 5-HT1B-induced behavioral effects in mice. Biol Psychiatry. 2009; 65: 401–408.Google Scholar
93. Shanahan, NA, Velez, LP, Masten, VL, Dulawa, SC. Essential role for orbitofrontal serotonin 1B receptors in obsessive-compulsive disorder-like behavior and serotonin reuptake inhibitor response in mice. Biol Psychiatry. 2011; 70: 1039–1048.Google Scholar
94. Koran, LM, Pallanti, S, Quercioli, L. Sumatriptan, 5-HT(1D) receptors and obsessive-compulsive disorder. Eur Neuropsychopharmacol. 2001; 11: 169–172.Google Scholar
95. Brown, SA, Crowell-Davis, S, Malcolm, T, Edwards, P. Naloxone-responsive compulsive tail chasing in a dog. J Am Vet Med Assoc. 1987; 190(7): 884–886.Google Scholar
96. Luescher, AU. Diagnosis and management of compulsive disorders in dogs and cats. Vet Clin North Am Small Anim Pract. 2003; 33(2): 253–267, vi.Google Scholar
97. Luescher, UA, McKeown, DB, Dean, H. A cross-sectional study on compulsive behaviour (stable vices) in horses. Equine Vet J Suppl. 1998; (27): 14–18.CrossRefGoogle ScholarPubMed
98. Swanepoel, N, Lee, E, Stein, DJ. Psychogenic alopecia in a cat: response to clomipramine. J S Afr Vet Assoc. 1998; 69(1): 22.Google Scholar
99. Grindlinger, HM, Ramsay, E. Compulsive feather picking in birds. Arch Gen Psychiatry. 1991; 48(9): 857.Google Scholar
100. Rapoport, JL, Ryland, DH, Kriete, M. Drug treatment of canine acral lick: an animal model of obsessive-compulsive disorder. Arch Gen Psychiatry. 1992; 49(7): 517–521.Google Scholar
101. Garner, JP, Weisker, SM, Dufour, B, Mench, JA. Barbering (fur and whisker trimming) by laboratory mice as a model of human trichotillomania and obsessive-compulsive spectrum disorders. Comp Med. 2004; 54(2): 216–224.Google Scholar
102. Garner, JP, Dufour, B, Gregg, LE, Weisker, SM, Mench, JA. Social and husbandry factors affecting the prevalence and severity of barbering (‘whisker trimming’) by laboratory mice. Applied Animal Behaviour Science. 2004; 89: 263–282.Google Scholar
103. Vermeire, S, Audenaert, K, De Meester, R, etal. Serotonin 2A receptor, serotonin transporter and dopamine transporter alterations in dogs with compulsive behaviour as a promising model for human obsessive-compulsive disorder. Psychiatry Res. 2012; 201(1): 78–87.Google Scholar
104. Powell, SB, Newman, HA, Pendergast, JF, Lewis, MH. A rodent model of spontaneous stereotypy: initial characterization of developmental, environmental, and neurobiological factors. Physiol Behav. 1999; 66: 355–363.Google Scholar
105. Korff, S, Stein, DJ, Harvey, BH. Stereotypic behaviour in the deer mouse: pharmacological validation and relevance for obsessive compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2008; 32: 348–355.Google Scholar
106. Bloch, MH, Landeros-Weisenberger, A, Kelmendi, B, etal. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Mol Psychiatry. 2006; 11(7): 622–632.Google Scholar
107. Presti, MF, Mikes, HM, Lewis, MH. Selective blockade of spontaneous motor stereotypy via intrastriatal pharmacological manipulation. Pharmacol Biochem Behav. 2003; 74(4): 833–839.Google Scholar
108. Presti, MF, Lewis, MH. Striatal opioid peptide content in an animal model of spontaneous stereotypic behavior. Behav Brain Res. 2005; 157(2): 363–368.Google Scholar
109. Korff, S, Stein, DJ, Harvey, BH. Cortico-striatal cyclic AMP-phosphodiesterase-4 signalling and stereotypy in the deer mouse: attenuation after chronic fluoxetine treatment. Pharmacol Biochem Behav. 2009; 92(3): 514–520.Google Scholar
110. Guldenpfennig, M, Wolmarans de, W, du Preez, JL, Stein, DJ, Harvey, BH. Cortico-striatal oxidative status, dopamine turnover and relation with stereotypy in the deer mouse. Physiol Behav. 2011; 103(3–4): 404–411.Google Scholar
111. Lynch, CB. Response to divergent selection for nesting behavior in Mus musculus. Genetics. 1980; 96: 757–765.Google Scholar
112. Greene-Schloesser, DM, Van der Zee, EA, Sheppard, DK, etal. Predictive validity of a non-induced mouse model of compulsive-like behavior. Behav Brain Res. 2011; 221(1): 55–62.Google Scholar
113. Hoffman, KL, Rueda Morales, RI. Toward an understanding of the neurobiology of “just right” perceptions: nest building in the female rabbit as a possible model for compulsive behavior and the perception of task completion. Behav Brain Res. 2009; 204: 182–191.Google Scholar
114. Hoffman, KL, Rueda Morales, RI. D1 and D2 dopamine receptor antagonists decrease behavioral bout duration, without altering the bout's repeated behavioral components, in a naturalistic model of repetitive and compulsive behavior. Behav Brain Res. 2012; 230: 1–10.Google Scholar
115. Woods, A, Smith, C, Szewczak, M, etal. Selective serotonin re-uptake inhibitors decrease schedule-induced polydipsia in rats: a potential model for obsessive compulsive disorder. Psychopharmacology. 1993; 112(2–3): 195–198.Google Scholar
116. Altemus, M, Glowa, JR, Galliven, E, Leong, YM, Murphy, DL. Effects of serotonergic agents on food-restriction-induced hyperactivity. Pharmacol Biochem Behav. 1996; 53(1): 123–131.Google Scholar
117. Njung'e, K, Handley, SL. Evaluation of marble-burying behavior as a model of anxiety. Pharmacol Biochem BehavJan 1991; 38(1): 63–67.Google Scholar
118. Holland, HC. Displacement activity as a form of abnormal behavior in animals. In: Beech HR, ed. Obsessional States. London: Methuen; 1974: 61–173.Google Scholar
119. Pitman, RK. Animal models of compulsive behavior. Biol Psychiatry. 1989; 26(2): 189–198.Google Scholar
120. Robbins, TW, Koob, GF. Selective disruption of displacement behaviour by lesions of the mesolimbic dopamine system. Nature. 1980; 285(5764): 409–412.Google Scholar
121. van Kuyck, K, Brak, K, Das, J, Rizopoulos, D, Nuttin, B. Comparative study of the effects of electrical stimulation in the nucleus accumbens, the mediodorsal thalamic nucleus and the bed nucleus of the stria terminalis in rats with schedule-induced polydipsia. Brain Res. 2008; 1201: 93–99.CrossRefGoogle ScholarPubMed
122. Huff, W, Lenartz, D, Schormann, M, etal. Unilateral deep brain stimulation of the nucleus accumbens in patients with treatment-resistant obsessive-compulsive disorder: outcomes after one year. Clin Neurol Neurosurg. 2010; 112(2): 137–143.Google Scholar
123. Rachman, S, Hodgson, R. Obsessions and Compulsions. New York: Prentice Hall; 1980.Google Scholar
124. Rasmussen, SA, Eisen, JL. The epidemiology and clinical features of obsessive compulsive disorder. Psychiatr Clin North Am. 1992; 15(4): 743–758.Google Scholar
125. Milad, MR, Rauch, SL. Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways. Trends Cogn Sci. 2012; 16(1): 43–51.Google Scholar
126. Franklin, ME, Foa, EB. Treatment of obsessive compulsive disorder. Ann Rev Clin Psychol. 2011; 7: 229–243.Google Scholar
127. Brunet, A, Ashbaugh, AR, Saumier, D, etal. Does reconsolidation occur in humans: a reply. Front Behav Neurosc. 2011; 5: 74.Google Scholar
128. Ganasen, KA, Ipser, JC, Stein, DJ. Augmentation of cognitive behavioral therapy with pharmacotherapy. Psychiatr Clin North Am. 2010; 33(3): 687–699.Google Scholar
129. Rodriguez-Romaguera, J, Do Monte, FH, Quirk, GJ. Deep brain stimulation of the ventral striatum enhances extinction of conditioned fear. Proc Natl Acad Sci U S A. 2012; 109(22): 8764–8769.Google Scholar
130. Joel, D, Avisar, A. Excessive lever pressing following post-training signal attenuation in rats: a possible animal model of obsessive compulsive disorder? Behav Brain Res. 2001; 123(1): 77–87.Google Scholar
131. Joel, D. The signal attenuation rat model of obsessive-compulsive disorder: a review. Psychopharmacology. 2006; 186(4): 487–503.Google Scholar
132. Albelda, N, Joel, D. Current animal models of obsessive compulsive disorder: an update. Neuroscience. 2012; 211: 83–106.Google Scholar
133. Albelda, N, Joel, D. Animal models of obsessive-compulsive disorder: exploring pharmacology and neural substrates. Neurosci Biobehav Rev. 2012; 36(1): 47–63.CrossRefGoogle ScholarPubMed
134. Joel, D, Ben-Amir, E, Doljansky, J, Flaisher, S. ‘Compulsive’ lever-pressing in rats is attenuated by the serotonin re-uptake inhibitors paroxetine and fluvoxamine but not by the tricyclic antidepressant desipramine or the anxiolytic diazepam. Behav Pharmacol. 2004; 15(3): 241–252.Google Scholar
135. Butter, CM, Mishkin, M, Rosvold, HE. Conditioning and extinction of a food-rewarded response after selective ablations of frontal cortex in rhesus monkeys. Exp Neurol. 1963; 7: 65–75.Google Scholar
136. Kolb, B, Nonneman, AJ, Singh, RK. Double dissociation of spatial impairments and perseveration following selective prefrontal lesions in rats. J Comp Physiol Psychol. 1974; 87(4): 772–780.Google Scholar
137. Nonneman, AJ, Voigt, J, Kolb, BE. Comparisons of behavioral effects of hippocampal and prefrontal cortex lesions in the rat. J Comp Physiol Psychol. 1974; 87(2): 249–260.Google Scholar
138. Izquierdo, A, Murray, EA. Opposing effects of amygdala and orbital prefrontal cortex lesions on the extinction of instrumental responding in macaque monkeys. Eur J Neurosci. 2005; 22(9): 2341–2346.Google Scholar
139. Bouton, ME. Context, ambiguity, and unlearning: sources of relapse after behavioral extinction. Biol Psychiatry. 2002; 52(10): 976–986.Google Scholar
140. Chudasama, Y, Passetti, F, Rhodes, SE, etal. Dissociable aspects of performance on the 5-choice serial reaction time task following lesions of the dorsal anterior cingulate, infralimbic and orbitofrontal cortex in the rat: differential effects on selectivity, impulsivity and compulsivity. Behav Brain Res. 2003; 146(1–2): 105–119.Google Scholar
141. Rogers, RD, Baunez, C, Everitt, BJ, Robbins, TW. Lesions of the medial and lateral striatum in the rat produce differential deficits in attentional performance. Behav Neurosci. 2001; 115: 799–811.Google Scholar
142. Baunez, C, Robbins, TW. Effects of transient inactivation of the subthalamic nucleus by local muscimol and APV infusions on performance on the five-choice serial reaction time task in rats. Psychopharmacology. 1999; 141(1): 57–65.Google Scholar
143. Boulougouris, V, Dalley, JW, Robbins, TW. Effects of orbitofrontal, infralimbic and prelimbic cortical lesions on serial spatial reversal learning in the rat. Behav Brain Res. 2007; 179(2): 219–228.Google Scholar
144. Clarke, HF, Robbins, TW, Roberts, AC. Lesions of the medial striatum in monkeys produce perseverative impairments during reversal learning similar to those produced by lesions of the orbitofrontal cortex. J Neurosci. 2008; 28(43): 10972–10982.Google Scholar
145. Castane, A, Theobald, DE, Robbins, TW. Selective lesions of the dorsomedial striatum impair serial spatial reversal learning in rats. Behav Brain Res. 2010; 210(1): 74–83.Google Scholar
146. Clarke, HF, Walker, SC, Dalley, JW, Robbins, TW, Roberts, AC. Cognitive inflexibility after prefrontal serotonin depletion is behaviorally and neurochemically specific. Cereb Cortex. 2007; 17(1): 18–27.Google Scholar
147. Boulougouris, V, Castane, A, Robbins, TW. Dopamine D2/D3 receptor agonist quinpirole impairs spatial reversal learning in rats: investigation of D3 receptor involvement in persistent behavior. Psychopharmacology. 2009; 202(4): 611–620.Google Scholar
148. Birrell, JM, Brown, VJ. Medial frontal cortex mediates perceptual attentional set shifting in the rat. J Neurosci. 2000; 20(11): 4320–4324.Google Scholar
149. Kehagia, AA, Murray, GK, Robbins, TW. Learning and cognitive flexibility: frontostriatal function and monoaminergic modulation. Curr Opin Neurobiol. 2010; 20(2): 199–204.Google Scholar
150. Veale, DM, Sahakian, BJ, Owen, AM, Marks, IM. Specific cognitive deficits in tests sensitive to frontal lobe dysfunction in obsessive-compulsive disorder. Psychol Med. 1996; 26(6): 1261–1269.Google Scholar
151. Watkins, LH, Sahakian, BJ, Robertson, MM, etal. Executive function in Tourette's syndrome and obsessive-compulsive disorder. Psychol Med. 2005; 35(4): 571–582.Google Scholar
152. Chamberlain, SR, Fineberg, NA, Menzies, LA, etal. Impaired cognitive flexibility and motor inhibition in unaffected first-degree relatives of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007; 164(2): 335–338.Google Scholar
153. Chamberlain, SR, Fineberg, NA, Blackwell, AD, Robbins, TW, Sahakian, BJ. Motor inhibition and cognitive flexibility in obsessive-compulsive disorder and trichotillomania. Am J Psychiatry. 2006; 163(7): 1282–1284.Google Scholar
154. Odlaug, BL, Chamberlain, SR, Grant, JE. Motor inhibition and cognitive flexibility in pathologic skin picking. Prog Neuropsychopharmacol Biol Psychiatry. 2010; 34(1): 208–211.Google Scholar
155. Chamberlain, SR, Robbins, TW. Noradrenergic modulation of cognition: therapeutic implications. J Psychopharmacol. 2013; 27(8): 694–718.CrossRefGoogle ScholarPubMed
156. Dias, R, Robbins, TW, Roberts, AC. Dissociation in prefrontal cortex of affective and attentional shifts. Nature. 1996; 380(6569): 69–72.Google Scholar
157. Brown, VJ, Bowman, EM. Rodent models of prefrontal cortical function. Trends Neurosci. 2002; 25(7): 340–343.Google Scholar
158. Hampshire, A, Owen, AM. Fractionating attentional control using event-related fMRI. Cereb Cortex. 2006; 16(12): 1679–1689.CrossRefGoogle ScholarPubMed
159. Menzies, L, Chamberlain, SR, Laird, AR, etal. Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited. Neurosci Biobehav Rev. 2008; 32(3): 525–549.Google Scholar
160. Clarke, HF, Walker, SC, Crofts, HS, etal. Prefrontal serotonin depletion affects reversal learning but not attentional set shifting. J Neurosci. 2005; 25(2): 532–538.Google Scholar
161. Chamberlain, SR, Muller, U, Blackwell, AD, etal. Neurochemical modulation of response inhibition and probabilistic learning in humans. Science. 2006; 311(5762): 861–863.Google Scholar
162. Tait, DS, Brown, VJ, Farovik, A, etal. Lesions of the dorsal noradrenergic bundle impair attentional set-shifting in the rat. Eur J Neurosci. 2007; 25(12): 3719–3724.Google Scholar
163. Lapiz, MDS, Bondi, CO, Morilak, DA. Chronic treatment with desipramine improves cognitive performance of rats in an attentional set-shifting test. Neuropsychopharmacology. 2007; 32: 1000–1010.Google Scholar
164. Zohar, J, Insel, TR. Obsessive-compulsive disorder: psychobiological approaches to diagnosis, treatment, and pathophysiology. Biol Psychiatry. 1987; 22(6): 667–687.Google Scholar
165. Robbins, TW, Roberts, AC. Differential regulation of fronto-executive function by the monoamines and acetylcholine. Cereb Cortex. 2007; 17(suppl 1): 151–160.Google Scholar
166. Tunbridge, EM, Bannerman, DM, Sharp, T, Harrison, PJ. Catechol-o-methyltransferase inhibition improves set-shifting performance and elevates stimulated dopamine release in the rat prefrontal cortex. J Neurosci. 2004; 24(23): 5331–5335.Google Scholar
167. Aron, AR, Durston, S, Eagle, DM, etal. Converging evidence for a fronto-basal-ganglia network for inhibitory control of action and cognition. J Neurosci. 2007; 27(44): 11860–11864.Google Scholar
168. Mallet, L, Polosan, M, Jaafari, N, etal. Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med. 2008; 359(20): 2121–2134.Google Scholar
169. Klavir, O, Flash, S, Winter, C, Joel, D. High frequency stimulation and pharmacological inactivation of the subthalamic nucleus reduces ‘compulsive’ lever-pressing in rats. Exp Neurol. 2009; 215(1): 101–109.Google Scholar
170. Eagle, DM, Baunez, C, Hutcheson, DM, etal. Stop-signal reaction-time task performance: role of prefrontal cortex and subthalamic nucleus. Cereb Cortex. 2008; 18(1): 178–188.CrossRefGoogle ScholarPubMed
171. Eagle, DM, Robbins, TW. Lesions of the medial prefrontal cortex or nucleus accumbens core do not impair inhibitory control in rats performing a stop-signal reaction time task. Behav Brain Res. 2003; 146(1–2): 131–144.Google Scholar
172. Eagle, DM, Robbins, TW. Inhibitory control in rats performing a stop-signal reaction-time task: effects of lesions of the medial striatum and d-amphetamine. Behav Neurosci. 2003; 117(6): 1302–1317.Google Scholar
173. Grant, JE, Odlaug, BL, Chamberlain, SR. Neurocognitive response to deep brain stimulation for obsessive-compulsive disorder: a case report. Am J Psychiatry. 2011; 168(12): 1338–1339.Google Scholar
174. Chamberlain, SR, Fineberg, NA, Blackwell, AD, etal. A neuropsychological comparison of obsessive-compulsive disorder and trichotillomania. Neuropsychologia. 2007; 45(4): 654–662.Google Scholar
175. Chamberlain, SR, Sahakian, BJ. The neuropsychiatry of impulsivity. Curr Opin Psychiatry. 2007; 20(3): 255–261.Google Scholar
176. Eagle, DM, Bari, A, Robbins, TW. The neuropsychopharmacology of action inhibition: cross-species translation of the stop-signal and go/no-go tasks. Psychopharmacology. 2008; 199(3): 439–456.Google Scholar
177. Bari, A, Eagle, DM, Mar, AC, Robinson, ES, Robbins, TW. Dissociable effects of noradrenaline, dopamine, and serotonin uptake blockade on stop task performance in rats. Psychopharmacology. 2009; 205(2): 273–283.Google Scholar
178. Dickinson, A. Actions and habits: the development of behavioural autonomy. Philos Trans R Soc Lond. 1985; 308: 67–78.Google Scholar
179. Balleine, BW. Sensation, incentive learning, and the motivational control of goal-directed action. In: Gottfried JA, ed. Neurobiology of Sensation and Reward. Boca Raton, FL, 2011; 287–310.Google Scholar
180. Balleine, BW, O'Doherty, JP. Human and rodent homologies in action control: corticostriatal determinants of goal-directed and habitual action. Neuropsychopharmacology. 2010; 35(1): 48–69.Google Scholar
181. Corbit, LH, Balleine, BW. The role of prelimbic cortex in instrumental conditioning. Behav Brain Res. 2003; 146(1–2): 145–157.Google Scholar
182. Tricomi, E, Balleine, BW, O'Doherty, JP. A specific role for posterior dorsolateral striatum in human habit learning. Eur J Neurosci. 2009; 29(11): 2225–2232.Google Scholar
183. Balleine, BW, Dickinson, A. Goal-directed instrumental action: contingency and incentive learning and their cortical substrates. Neuropharmacology. 1998; 37(4–5): 407–419.Google Scholar
184. Yin, HH, Ostlund, SB, Knowlton, BJ, Balleine, BW. The role of the dorsomedial striatum in instrumental conditioning. Eur J Neurosci. 2005; 22(2): 513–523.Google Scholar
185. Valentin, VV, Dickinson, A, O'Doherty, JP. Determining the neural substrates of goal-directed learning in the human brain. J Neurosci. 2007; 27(15): 4019–4026.Google Scholar
186. Tanaka, SC, Balleine, BW, O'Doherty, JP. Calculating consequences: brain systems that encode the causal effects of actions. J Neurosci. 2008; 28(26): 6750–6755.Google Scholar
187. Haber, SN, Kim, KS, Mailly, P, Calzavara, R. Reward-related cortical inputs define a large striatal region in primates that interface with associative cortical connections, providing a substrate for incentive-based learning. J Neurosci. 2006; 26(32): 8368–8376.Google Scholar
188. Ongur, D, Price, JL. The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cereb Cortex. 2000; 10(3): 206–219.Google Scholar
189. Yin, HH, Knowlton, BJ. The role of the basal ganglia in habit formation. Nat Rev Neurosci. 2006; 7(6): 464–476.Google Scholar
190. Gillan, CM, Papmeyer, M, Morein-Zamir, S, etal. Disruption in the balance between goal-directed behavior and habit learning in obsessive-compulsive disorder. Am J Psychiatry. 2011; 168(7): 718–726.Google Scholar
191. Gillan, CM, Morein-Zamir, S, Urcelay, GP, etal. Enhanced avoidance habits in obsessive-compulsive disorder. Biol Psychiatry. In press. DOI: 10.1016/j.biopsych.2013.02.002.Google Scholar
192. Gottesman, II, Gould, TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry. 2003; 160(4): 636–645.Google Scholar
193. Chamberlain, SR, Menzies, L. Endophenotypes of obsessive-compulsive disorder: rationale, evidence and future potential. Expert Rev Neurother. 2009; 9(8): 1133–1146.Google Scholar
194. Menzies, L, Achard, S, Chamberlain, SR, etal. Neurocognitive endophenotypes of obsessive-compulsive disorder. Brain. 2007; 130(Pt 12): 3223–3236.Google Scholar
195. Chen, SK, Tvrdik, P, Peden, E, etal. Hematopoietic origin of pathological grooming in Hoxb8 mutant mice. Cell. 2010; 141(5): 775–785.Google Scholar
196. Ichimaru, Y, Egawa, T, Sawa, A. 5-HT1A-receptor subtype mediates the effect of fluvoxamine, a selective serotonin reuptake inhibitor, on marble-burying behavior in mice. Jpn J Pharmacol. 1995; 68(1): 65–70.Google Scholar
197. Broekkamp, CL, Rijk, HW, Joly-Gelouin, D, Lloyd, KL. Major tranquillizers can be distinguished from minor tranquillizers on the basis of effects on marble burying and swim-induced grooming in mice. Eur J Pharmacol. 1986; 126(3): 223–229.Google Scholar
198. Boulougouris, V, Robbins, TW. Enhancement of spatial reversal learning by 5-HT2C receptor antagonism is neuroanatomically specific. J Neurosci. 2010; 30(3): 930–938.Google Scholar
199. Nikiforuk, A. Selective blockade of 5-HT7 receptors facilitates attentional set-shifting in stressed and control rats. Behav Brain Res. 2012; 226(1): 118–123.Google Scholar
200. Cain, RE, Wasserman, MC, Waterhouse, BD, McGaughy, JA. Atomoxetine facilitates attentional set shifting in adolescent rats. Dev Cogn Neurosci. 2011; 1(4): 552–559.Google Scholar
201. Bari, A, Mar, AC, Theobald, DE, etal. Prefrontal and monoaminergic contributions to stop-signal task performance in rats. J Neurosci. 2011; 31(25): 9254–9263.Google Scholar
202. Chamberlain, SR, Müller, U, Blackwell, AD, etal. Neurochemical modulation of response inhibition and probabilistic learning in humans. Science. 2006; 311(5762): 861–863.Google Scholar
203. Chamberlain, SR, Hampshire, A, Muller, U, etal. Atomoxetine modulates right inferior frontal activation during inhibitory control: a pharmacological functional magnetic resonance imaging study. Biol Psychiatry. 2009; 65(7): 550–555.Google Scholar
204. Gillan, CM, Morein-Zamir, S, Kaser, M, etal. Counterfactual processing of economic action-outcome alternatives in obsessive-compulsive disorder: further evidence of impaired goal-directed behavior. Biol Psychiatry. In press. DOI: 10.1016/j.biopsych.2013.01.018.Google Scholar