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Nestler EJ, Hyman SE. Animal models of neuropsychiatric disorders. Nat Neurosci . 2010 Oct 1 ; 13(10):1161-9. PubMed Abstract

Comments on Paper and Primary News
Comment by:  Jared Young
Submitted 12 November 2010 Posted 12 November 2010

Nestler and Hyman present a sobering but valuable addition to the literature on developing animal models of neuropsychiatric disorders. Quite rightly, they highlight the need for developing such animal models because there are limitations on investigating specific functions of the living human brain. Although the authors cover a broad range of possibilities given the title, they focus on the challenges ahead, astutely warning of complacency when attempting to develop or use animal models.

While warnings of the difficulty of creating animal models based on DSM-IV criteria are not unknown, reminding researchers remains useful. The key to this review was, however, to put animal modeling into context. Nestler and Hyman call for researchers from all areas to consider whether they are working/trying to publish a good model of disease or a tool to investigate the neurobiology of behavior. As I have pointed out to many who have asked, I have used α7 nicotinic acetylcholine receptor knockout (KO) mice as a tool to understand the contribution of this receptor to behavior, and...  Read more

View all comments by Jared Young

Comment by:  Jo Neill
Submitted 17 November 2010 Posted 17 November 2010

This is a welcome review article on an important topic. The key point being addressed is that the lack of improved therapy for psychiatric illness is due to the lack of carefully validated animal models. As described by the authors, testing a drug in the appropriate animal model is a critical stage in the development of new therapies for illnesses, particularly those defined by altered emotional states and marked behavioral changes, as described by the DSM (current version IV).

The review describes the challenges and limitations faced by scientists in this field, such as the difficulty identifying the pathology of human brain disorders. Importantly, the review focuses on the necessity for development of better animal models for identifying improved therapies, and discusses limitations of the current models. These include incomplete validation and poor predictive validity, both of which present considerable difficulties when looking for novel targets and treatments. However, there are two key reasons for the limitations of the current models that are not fully explored by...  Read more

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Comment by:  Hugo Geerts
Submitted 26 November 2010 Posted 26 November 2010
  I recommend this paper

The excellent review paper by Nestler and Heyman on animal models in psychiatric disorders illustrates the current problems with finding new and innovative treatments for patients. The current perception is that psychiatric diseases are so difficult to model that more and more pharmaceutical companies are leaving the psychiatry domain.

Although animal models are great to elucidate the biology of physiological processes, on top of their limited predictivity for the clinical situation, they have a number of underestimated limitations in drug discovery and development (Geerts, 2009). These limitations include 1) differences in neurotransmitter circuitry (i.e., receptor distribution), 2) the incomplete representation of the full human pathology, 3) the absence in animal models of important functional genotypes that might interfere with the primary pharmacology, 4) the pharmacodynamic interference of allowed co-medications in clinical trials, 5) the difference in drug affinities between rat and human subtype receptors (sometimes...  Read more

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