Neuro

Psychiatr Clin N Am 29 (2006) 371–390

Animal Models of Obsessive-Compulsive Disorder: Rationale to Understanding Psychobiology and Pharmacology
Schaun Korff, MSc, Brian H. Harvey, BPharm, PhD*
Division of Pharmacology, School of Pharmacy, North-West University, Potchefstroom 2520, South Africa

Animal models have proved extremely useful in assisting researchers to better understand a givenclinical disorder. The difficulty in developing a suitable animal model lies in whether it can be assumed that an animal is truly exhibiting the behavioral and other manifestations of the human disorder it is designed to model. An animal model can never reflect fully the human situation that it is modeling, nor is there a model that is isomorphic with the symptomology in question (ie, the animalsymptoms are similar but the cause of the symptoms differ between human and model) [1]. Consequently, the development of an animal model requires parallel development of measures that will allow meaningful comparisons. Difficulties in setting up and identifying suitable animal models include the intrinsic problems in defining patient profiles and diagnostic criteria, variations between patients even whenthese are pathologically defined, and the possibility that the level of the disorder that the animal exhibits may not be equivalent in the human disorder. Even when it can be certain that the behaviors or signs are the same, humans are unusual in that they are verbal and so similar behaviors, signals, or signs may have different meanings. Furthermore, the observable changes in behavior that occur inanimals, primarily rodents, are treated as secondary symptoms in humans [2], and little effort is made to characterize either human or animal behaviors in a manner that would allow assessment of analogy or homology. For example, hiding is normal behavior in many rodents but is considered

This work has been supported by the South African Medical Research Council (MRC). * Corresponding author.E-mail address: fklbhh@puk.ac.za (B.H. Harvey). 0193-953X/06/$ - see front matter Ó 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.psc.2006.02.007 psych.theclinics.com

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pathologic in humans; therefore the usefulness of the animal model in mimicking the human condition is limited [2]. In recent years, an understanding of obsessive-compulsive disorder (OCD) as acognitive-behavioral disorder with a close functional relationship with other related disorders has emerged. Thus, OCD is characterized by intrusive thoughts or images (obsessions) that increase anxiety and by ritualistic actions (compulsions) that decrease anxiety. Most patients who have OCD are aware of the irrationality of their thoughts and behaviors and thus unwillingly partake in stereotypedbehavior even though they recognize that the obsessions and impulses are the product of their own minds. These internal conflicts cause immeasurable anxiety in individuals suffering from OCD [3]. At a phenomenologic or psychologic level, OCD demonstrates a continuum with a broad range of other conditions (eg, on a spectrum of rewardrelated or affective disorders [4,5], on a spectrum ofcompulsive-impulsive disorders [6–9,10], or on a spectrum of stereotypic disorders [11]). Moreover, the behaviors associated with OCD have been linked to a wide variety of cognitive [12,13] and occasionally noncognitive deficits [14], including a fundamental impairment of executive function ability, deficits of immediate and secondary memory, and spatial information processing. The disorder therefore is extremelycomplex, with diverse neurologic manifestations, including neuropsychologic symptoms such as cognitive and noncognitive deficits, neuromotor symptoms such as stereotypy, and presentation with prominent symptoms of anxiety. Accordingly, OCD is a highly heterogeneous condition, and it has been suggested that it is actually composed of several distinct subtypes, as described in Table 1. Despite the...