Elsevier

Neuroscience

Volume 211, 1 June 2012, Pages 83-106
Neuroscience

Review
Current animal models of obsessive compulsive disorder: an update

https://doi.org/10.1016/j.neuroscience.2011.08.070Get rights and content

Abstract

During the last 30 years there have been many attempts to develop animal models of obsessive compulsive disorder (OCD), in the hope that they may provide a route for furthering our understanding and treatment of this disorder. The present review provides the reader with an overview of the currently active animal models of OCD, their strengths and limitations, so that the reader can use the review as a guide for establishing new animal models of OCD, evaluating existing animal models and choosing among them according to one's needs. We review current genetic, pharmacological, neurodevelopmental and behavioral animal models of OCD, and evaluate their face validity (derived from phenomenological similarity between the behavior in the animal model and the specific symptoms of the human condition), predictive validity (derived from similarity in response to treatment) and construct validity (derived from similarity in the underlying mechanisms [physiological or psychological]). On the basis of this evaluation we discuss the usefulness of the different models for screening drugs for anti-compulsive activity, detecting new targets for high frequency stimulation, studying the neural mechanisms of OCD and unraveling the role of gonadal hormones. We then describe potential new treatment strategies that emerge from the convergence of data obtained in different models on the one hand, and how different models can be used to model different subtypes or dimensions of OCD, on the other hand.

This article is part of a Special Issue entitled: Neuroscience Disease Models.

Highlights

▶We review currently active animal models of obsessive-compulsive disorder (OCD). ▶Provide a guide for establishing new/evaluating existent animal models of OCD. ▶Evaluate the validity of current animal models of OCD. ▶Describe potential new treatments emerging from convergence of data from different models. ▶Discuss modeling different subtypes or dimensions of OCD by different animal models.

Section snippets

Obsessive-compulsive disorder

OCD is a psychiatric affliction with a lifetime prevalence of 1–3% (Rasmussen and Eisen, 1992, Sasson et al., 1997). The Diagnostic and Statistical Manual of Mental Disorders (4th ed; DSM IV-TR) classifies OCD as an anxiety disorder characterized by obsessive thinking (persistent ideas, thoughts, impulses or images that are experienced as intrusive and inappropriate) and compulsive behavior (repetitive behaviors or mental acts [e.g. hand-washing, checking, praying, counting]) that are time

Criteria for validating animal models of OCD

Previous papers have provided a thorough discussion of criteria for the validation and evaluation of animal models of psychopathology in general (Geyer and Markow, 1995, Matthysse 1986, McKinney 1988, McKinney and Bunney 1969, Willner 1984, Willner 1986, Willner 1991) and of OCD in particular (Albelda and Joel, in press, Joel, 2006a). In the present paper we treat phenomenological similarity between the behavior in the animal model and the specific symptoms of the human condition as

Animal models of OCD

Animal models of OCD are typically divided into three classes according to the method used to induce compulsive-like behavior, namely, genetic, pharmacological or behavioral manipulation. Recently a neurodevelopmental model of OCD has been presented, and it represents the first model of a new class, neurodevelopmental models.

Conclusions

Table 1 summarizes our evaluation of the face, predictive and construct validity of each of the models reviewed. On the basis of this evaluation we discuss the usefulness of the different models for screening drugs for anti-compulsive activity, detecting new targets for high frequency stimulation, studying the neural mechanisms of OCD and unraveling the role of gonadal hormones. We then describe potential new treatment strategies that emerge from the convergence of data obtained in different

References (256)

  • B.H. Bewernick et al.

    Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression

    Biol Psychiatry

    (2010)
  • K.L. Bigos et al.

    Dysregulation of neurosteroids in obsessive compulsive disorder

    J Psychiatr Res

    (2009)
  • V. Boulougouris et al.

    Effects of orbitofrontal, infralimbic and prelimbic cortical lesions on serial spatial reversal learning in the rat

    Behavioural Brain Research

    (2007)
  • C.L. Broekkamp et al.

    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)
  • A. Broocks et al.

    Acute intravenous administration of ondansetron and m-CPP, alone and in combination, in patients with obsessive-compulsive disorder (OCD): behavioral and biological results

    Psychiatry Res

    (1998)
  • K.M. Campbell et al.

    Behavioral effects of cocaine on a transgenic mouse model of cortical-limbic compulsion

    Brain Res

    (1999)
  • K.M. Campbell et al.

    Differential response of cortical-limbic neuropotentiated compulsive mice to dopamine D1 and D2 receptor antagonists

    Eur J Pharmacol

    (1999)
  • S.R. Chamberlain et al.

    The neuropsychology of obsessive compulsive disorder: the importance of failures in cognitive and behavioural inhibition as candidate endophenotypic markers

    Neurosci Biobehav Rev

    (2005)
  • J.M. Chou-Green et al.

    Compulsive behavior in the 5-HT2C receptor knockout mouse

    Physiol Behav

    (2003)
  • Y. Chudasama et al.

    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)
  • L. Clark et al.

    Association between response inhibition and working memory in adult ADHD: a link to right frontal cortex pathology?

    Biol Psychiatry

    (2007)
  • R. Cools et al.

    Reversal learning in Parkinson's disease depends on medication status and outcome valence

    Neuropsychologia

    (2006)
  • V. Coric et al.

    Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial

    Biol Psychiatry

    (2005)
  • G. Di Giovanni et al.

    Serotonin-dopamine interaction: electrophysiological evidence

    Prog Brain Res

    (2008)
  • V. Di Matteo et al.

    Role of 5-HT2C receptors in the control of central dopamine function

    Trends Pharmacol Sci

    (2001)
  • K.T. Eddy et al.

    A multidimensional meta-analysis of psychotherapy and pharmacotherapy for obsessive-compulsive disorder

    Clin Psychol Rev

    (2004)
  • N. Egashira et al.

    Involvement of the sigma1 receptor in inhibiting activity of fluvoxamine on marble-burying behavior: comparison with paroxetine

    Eur J Pharmacol

    (2007)
  • N. Egashira et al.

    Effects of glutamate-related drugs on marble-burying behavior in mice: implications for obsessive-compulsive disorder

    Eur J Pharmacol

    (2008)
  • N. Egashira et al.

    Aripiprazole inhibits marble-burying behavior via 5-hydroxytryptamine (5-HT)1A receptor-independent mechanisms

    Eur J Pharmacol

    (2008)
  • R.E. Featherstone et al.

    The amphetamine-induced sensitized state as a model of schizophrenia

    Prog Neuro-Psychopharmacol Biol Psychiatry

    (2007)
  • A. Fernández-Guasti et al.

    Ovarian steroids counteract serotonergic drugs actions in an animal model of obsessive-compulsive disorder

    Psychoneuroendocrinology

    (2006)
  • S. Flaisher-Grinberg et al.

    Ovarian hormones modulate “compulsive” lever-pressing in female rats

    Horm Behav

    (2009)
  • J.P. Garner et al.

    Social and husbandry factors affecting the prevalence and severity of barbering ([‘]whisker trimming’) by laboratory mice

    Appl Anim Behav Sci

    (2004)
  • A.W. Goddard et al.

    Serotoninergic mechanisms in the treatment of obsessive-compulsive disorder

    Drug Discov Today

    (2008)
  • W.K. Goodman et al.

    m-Chlorophenylpiperazine in patients with obsessive-compulsive disorder: absence of symptom exacerbation

    Biol Psychiatry

    (1995)
  • L.R. Grad et al.

    Obsessive-compulsive symptomatology in children with Tourette's syndrome

    J Am Acad Child Adolesc Psychiatry

    (1987)
  • D.M. Greene-Schloesser et al.

    Predictive validity of a non-induced mouse model of compulsive-like behavior

    Behav Brain Res

    (2011)
  • J.M. Greer et al.

    Hoxb8 is required for normal grooming behavior in mice

    Neuron

    (2002)
  • M. Güldenpfennig et al.

    Cortico-striatal oxidative status, dopamine turnover and relation with stereotypy in the deer mouse

    Physiol Behav

    (2011)
  • P.B. Hedlund et al.

    The 5-HT7 receptor influences stereotypic behavior in a model of obsessive-compulsive disorder

    Neurosci Lett

    (2007)
  • R.A. Hill et al.

    Estrogen deficient male mice develop compulsive behavior

    Biol Psychiatry

    (2007)
  • K.L. Ho Pian et al.

    Effects of meta-chlorophenylpiperazine on cerebral blood flow in obsessive-compulsive disorder and controls

    Biol Psychiatry

    (1998)
  • S. Hogg et al.

    Acceleration of onset of action in schedule-induced polydipsia: combinations of SSRI and 5-HT1A and 5-HT1B receptor antagonists

    Pharmacol Biochem Behav

    (2004)
  • E. Hollander et al.

    Effects of chronic fluoxetine treatment on behavioral and neuroendocrine responses to meta-chlorophenylpiperazine in obsessive-compulsive disorder

    Psychiatry Res

    (1991)
  • W. Huff et al.

    Unilateral deep brain stimulation of the nucleus accumbens in patients with treatment-resistant obsessive-compulsive disorder: outcomes after one year

    Clin Neurol Neurosurg

    (2010)
  • E. Aboujaoude et al.

    Memantine augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial

    J Clin Psychopharmacol

    (2009)
  • Albelda N, Joel D (in press) Animal models of obsessive-compulsive disorder: exploring pharmacology and neural...
  • N. Albelda et al.

    The role of NMDA receptors in the signal attenuation rat model of obsessive–compulsive disorder

    Psychopharmacology

    (2010)
  • Diagnostic and statistical manual of mental disorders

    (2000)
  • B. Aouizerate et al.

    Deep brain stimulation of the ventral caudate nucleus in the treatment of obsessive-compulsive disorder and major depressionCase report

    J Neurosurg

    (2004)
  • Cited by (0)

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