Lost in translation? A critical look at the role that animal models of obsessive compulsive disorder play in current drug discovery strategies

ABSTRACT

Introduction: Obsessive-compulsive disorder (OCD) is a severe neuropsychiatric illness estimated to affect between 1–3% of the population. In today’s literature, there are a number well-validated and convincing animal models of OCD described.

Areas covered: Herein, the authors look at the role that animal models of OCD (including transgenic models, deer mouse stereotypy, quinpirole sensitization, post-training signal attenuation, and mouse marble burying) have played in determining the current directions of OCD drug discovery. Specifically, the article reviews new OCD drug therapies currently under investigation including drugs that target glutamate, dopamine, serotonin, and endocannabinoid systems. The authors review the published results of these clinical trials, and critically examine the contribution of animal models to the development of these novel therapies.

Expert opinion: Nitric oxide inhibitors, oxycarbazepine, and modulators of serotonin and metabotropic glutamate receptors should be further explored in animal models as well as in clinical trials. Pregabalin, topiramate, lamotrigine, sarcosine, minocycline, L-carnosine, celecoxib, and ondansetron, which have shown promise in clinical trials, should be explored in animal models with the goal of understanding the neurobiology of their effects. A multidisciplinary, interactive approach to OCD drug discovery, where animal models generate neurobiological hypotheses that can be tested in the clinic, and vice versa, should be cultivated.

KEYWORDS:

• OCD
• compulsion
• obsession
• animal model
• glutamate
• dopamine

Article highlights

• OCD is a severe and debilitating neuropsychiatric illness that affects up to three percent of the population.

• Novel OCD drugs currently under investigation include glutamate, endocannabinoid, and nitric oxide modulators, as well as antioxidant and anti-inflammatory agents.

• Mouse marble burying behavior often parallels OCD symptoms with respect to responsiveness to experimental drugs.

• Many well-validated animal models of OCD have been relatively under-utilized with respect to identifying and testing novel drug therapies.

• Animal models of OCD, model systems, and clinical studies should be considered as three interacting research domains for the generation and testing of hypotheses relevant to OCD drug discovery.

This box summarizes key points contained in the article.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This manuscript was not funded.