Journal
EXPERT OPINION ON DRUG DISCOVERY
Volume 16, Issue 7, Pages 791-806Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/17460441.2021.1877657
Keywords
Schizophrenia; animal models; behavior; sex differences; antipsychotics; drug development
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Schizophrenia is a severe psychiatric disorder that affects millions worldwide, with current treatment options not fully addressing the disease. Developing valid animal models for screening new drug targets appears to be challenging due to the elusive etiology of schizophrenia. Multi-model approaches and forward and reverse translation between preclinical and clinical research offer promise for developing new strategies in schizophrenia treatment.
Introduction: Schizophrenia is a severe psychiatric disorder affecting millions worldwide. However, available treatment options do not fully address the disease. Whereas current antipsychotics may control psychotic symptoms, they seem notoriously ineffective in improving negative and cognitive symptoms or in preventing functional decline. As the etiology of schizophrenia eludes us, the development of valid animal models for screening new drug targets appears to be a strenuous task. Areas covered: In this review, the authors present the key concepts that validate animal models of schizophrenia, as well as the different screening approaches for novel schizophrenia treatments. The models covered are either based on major neurotransmitter systems or neurodevelopmental, immune, and genetic approaches. Expert opinion: Sadly, due to inertia, research focuses on developing 'anti-psychotics', instead of 'anti-schizophrenia' drugs that would tackle the entire syndrome of schizophrenia. Whereas no perfect model may ever exist, combining different experimental designs may enhance validity, as the over-reliance on a single model is inappropriate. Multi-model approaches incorporating vulnerability, the 'two-hit' hypothesis, and endophenotypes offer a promise for developing new strategies for schizophrenia treatment. Forward and reverse translation between preclinical and clinical research will increase the probability of success and limit failures in drug development.
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