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Psychiatric disorders

Simulating schizophrenia

Nature Reviews Drug Discovery volume 5, page 284 (2006)Cite this article

Overactivity of dopamine 2 (D2) receptors has long been implicated in the pathophysiology of schizophrenia. Indeed, all effective antipsychotic drugs block D2 receptors and, in particular, improve the positive symptoms of the disease, such as hallucinations and delusions. However, these drugs typically only have modest beneficial effects on cognitive impairments associated with schizophrenia, such as deficits in working memory, and it has been more difficult to determine whether D2 receptors have any role in these symptoms.

To investigate this issue, Kellendonk and co-workers developed transgenic mice in which overexpression of D2 receptors was restricted to the striatum, as increased activity of D2 receptors in this area has been implicated in schizophrenia. Importantly, expression of the D2 receptor transgene could be 'switched off' by oral administration of the antibiotic doxycycline.

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ORIGINAL RESEARCH PAPER

  1. Kellendonk, C. et al. Transient and selective overexpression of dopamine D2 receptors in the striatum causes persistent abnormalities in prefrontal cortex functioning. Neuron 49, 603–615 (2006)

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  1. Samantha Barton
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Barton, S. Simulating schizophrenia. Nat Rev Drug Discov 5, 284 (2006). https://doi.org/10.1038/nrd2023

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  • DOI: https://doi.org/10.1038/nrd2023

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