Abstract
Rationale
Spontaneous (novel) object recognition (SOR) is one of the most widely used rodent behavioural tests. The opportunity for rapid data collection has made SOR a popular choice in studies that explore cognitive impairment in rodent models of schizophrenia, and that test the efficacy of drugs intended to reverse these deficits.
Objectives
We provide an overview of the many recent studies that have used SOR to explore the mnemonic effects of manipulation of the key transmitter systems relevant to schizophrenia—the dopamine, glutamate, GABA, acetylcholine, serotonin and cannabinoid systems—alone or in combination. We also review the use of SOR in studying memory in genetically modified mouse models of schizophrenia, as well as in neurodevelopmental and lesion models. We end by discussing the construct and predictive validity, and translational relevance, of SOR with respect to cognitive impairment in schizophrenia.
Results
Perturbation of the dopamine or glutamate systems can generate robust and reliable impairment in SOR. Impaired performance is also seen following antagonism of the muscarinic acetylcholine system, or exposure to cannabinoid agonists. Cognitive enhancement has been reported using alpha7-nicotinic acetylcholine receptor agonists and 5-HT6 antagonists. Among non-pharmacological models, neonatal ventral hippocampal lesions and maternal immune activation can impair SOR, while mixed results have been obtained with mice carrying mutations in schizophrenia risk-associated genes, including neuregulin and COMT.
Conclusions
While SOR is not without its limitations, the task represents a useful method for studying manipulations with relevance to cognitive impairment in schizophrenia, as well as the interactions between them.
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Notes
There is evidence to suggest that the same structures within the temporal lobe mediate both memory for objects and perceptual discrimination between them (e.g. Cowell et al. 2006; Bussey and Saksida 2005). Thus, perirhinal cortex lesions impair SOR at longer but not shorter delays when standard objects are used, but when perceptually similar objects are used such lesions can produce impairments when there is little or no delay (Bartko et al. 2007). Nevertheless, short delays should be included in experiments using standard objects to rule out gross perceptual (e.g. visual acuity) deficits as a possible reason for impairment at longer delays.
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Acknowledgements
The authors would like to thank Prof. Trevor Robbins and Dr. Mark Tricklebank for comments on an earlier version of the manuscript. This work has received support from the Innovative Medicine Initiative Joint Undertaking under grant agreement n° 115008 of which resources are composed of EFPIA in‐kind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007‐2013).
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Lyon, L., Saksida, L.M. & Bussey, T.J. Spontaneous object recognition and its relevance to schizophrenia: a review of findings from pharmacological, genetic, lesion and developmental rodent models. Psychopharmacology 220, 647–672 (2012). https://doi.org/10.1007/s00213-011-2536-5
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DOI: https://doi.org/10.1007/s00213-011-2536-5