L Lyon1, L M Saksida, T J Bussey. 1. Department of Experimental Psychology, University of Cambridge, Downing St, Cambridge, CB2 3EB, UK.
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-HT(6) 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.
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-HT(6) 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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