Prepulse inhibition predicts spatial working memory performance in the inbred Roman high- and low-avoidance rats and in genetically heterogeneous NIH-HS rats: relevance for studying pre-attentive and cognitive anomalies in schizophrenia.
Animal models of schizophrenia-relevant symptoms are increasingly important for progress in our understanding of the neurobiological basis of the disorder and for discovering novel and more specific treatments. Prepulse inhibition (PPI) and working memory, which are impaired in schizophrenic patients, are among the symptoms/processes modeled in those animal analogs. We have evaluated whether a genetically-selected rat model, the Roman high-avoidance inbred strain (RHA-I), displays PPI deficits as compared with its Roman low-avoidance (RLA-I) counterpart and the genetically heterogeneous NIH-HS rat stock. We have investigated whether PPI deficits predict spatial working memory impairments (in the Morris water maze; MWM) in these three rat types (Experiment 1), as well as in a separate sample of NIH-HS rats stratified according to their extreme (High, Medium, Low) PPI scores (Experiment 2). The results from Experiment 1 show that RHA-I rats display PPI and spatial working memory deficits compared to both RLA-I and NIH-HS rats. Likewise, in Experiment 2, "Low-PPI" NIH-HS rats present significantly impaired working memory with respect to "Medium-PPI" and "High-PPI" NIH-HS subgroups. Further support to these results comes from correlational, factorial, and multiple regression analyses, which reveal that PPI is positively associated with spatial working memory performance. Conversely, cued learning in the MWM was not associated with PPI. Thus, using genetically-selected and genetically heterogeneous rats, the present study shows, for the first time, that PPI is a positive predictor of performance in a spatial working memory task. These results may have translational value for schizophrenia symptom research in humans, as they suggest that either by psychogenetic selection or by focusing on extreme PPI scores from a genetically heterogeneous rat stock, it is possible to detect a useful (perhaps "at risk") phenotype to study cognitive anomalies linked to schizophrenia.
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, School of Medicine, Institute of Neurosciences, Autonomous University of Barcelona Barcelona, Spain.
Ignasi
I
Oliveras
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, School of Medicine, Institute of Neurosciences, Autonomous University of Barcelona Barcelona, Spain.
Cristóbal
C
Río-Álamos
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, School of Medicine, Institute of Neurosciences, Autonomous University of Barcelona Barcelona, Spain.
Toni
T
Cañete
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, School of Medicine, Institute of Neurosciences, Autonomous University of Barcelona Barcelona, Spain.
Gloria
G
Blázquez
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, School of Medicine, Institute of Neurosciences, Autonomous University of Barcelona Barcelona, Spain.
Esther
E
Martínez-Membrives
Section of Pharmaceutical, Pharmacological and Nutraceutical Sciences, Department of Life and Environmental Sciences, University of Cagliari Cagliari, Italy.
Osvaldo
O
Giorgi
Section of Pharmaceutical, Pharmacological and Nutraceutical Sciences, Department of Life and Environmental Sciences, University of Cagliari Cagliari, Italy.
Maria G
MG
Corda
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, School of Medicine, Institute of Neurosciences, Autonomous University of Barcelona Barcelona, Spain.
Adolf
A
Tobeña
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, School of Medicine, Institute of Neurosciences, Autonomous University of Barcelona Barcelona, Spain.
Alberto
A
Fernández-Teruel
Roman high-avoidance rats; Roman low-avoidance rats; cognitive deficits; genetically heterogeneous rats; prepulse inhibition; schizophrenia-relevant symptoms; schizophreniform rat model; spatial working memory