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Mouse pharmacological models of cognitive disruption relevant to schizophrenia
Jared W Young1, Susan B Powell, Mark A Geyer
1Department of Psychiatry, University of California San Diego, 9500 Gilman Drive MC 0804, La Jolla, CA 92093-0804, USA. jaredyoung@ucsd.edu
Abstract:
Schizophrenia is a debilitating cognitive disorder. The link between cognitive debilitation and functional outcome in patients with schizophrenia has prompted research to develop procognitive therapies. It is hoped that by improving cognition in these patients, their functional outcome will also improve. Although no established treatments exist as yet, progress has been made toward understanding how to evaluate putative compounds in the clinic. Genetic mouse models and pharmacological rat models of cognitive disruption are being developed that may help to evaluate these putative compounds preclinically. Considering the increased number of genetic mouse models relevant to schizophrenia, there is a need to evaluate pharmacological manipulations on cognition in mice. Here we review the current literature on mouse pharmacological models relevant to schizophrenia. In this review, we discuss where different pharmacological effects between rats and mice on cognitive tasks are observed and assess the validity offered by these models. We conclude that the predictive validity of these models is currently difficult to assess and that much more needs to be done to develop useful mouse pharmacological models of cognitive disruption in schizophrenia.
Insights
Developing effective procognitive therapies for schizophrenia requires reliable preclinical models. Current mouse models show promise but need further development to accurately predict treatment efficacy for cognitive deficits in schizophrenia.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Schizophrenia significantly impairs cognition, impacting patient functional outcomes.
- Developing procognitive therapies is a key research goal to improve schizophrenia treatment.
- Preclinical models are crucial for evaluating potential procognitive compounds.
Purpose of the Study:
- To review the current literature on pharmacological mouse models of cognitive disruption in schizophrenia.
- To assess the validity and limitations of these mouse models compared to rat models.
- To identify needs for developing more effective mouse models for schizophrenia research.
Main Methods:
- Literature review of pharmacological manipulations on cognition in mouse models relevant to schizophrenia.
- Comparison of observed pharmacological effects on cognitive tasks between rats and mice.
- Assessment of the predictive validity of current mouse models.
Main Results:
- Pharmacological effects on cognitive tasks can differ between rats and mice.
- The predictive validity of existing mouse pharmacological models for schizophrenia is currently challenging to ascertain.
- There is a growing number of genetic mouse models relevant to schizophrenia.
Conclusions:
- Further research is essential to develop robust mouse pharmacological models for cognitive disruption in schizophrenia.
- Current models require refinement to reliably predict therapeutic efficacy.
- Addressing species-specific differences in pharmacological responses is critical.
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