The aim of this study was to assess the mechanisms underlying behavioural differences between high- (HR) and low- (LR) anxiety rats, selected according to their behaviour in the contextual fear test (i.e., the duration of the freezing response was used as a discriminating variable), after a chronic restraint procedure (21days, 3h daily). We analysed the expression of the GluN2B subunits of the NMDA and glucocorticoid receptors (GRs) in selected brain structures (immunofluorescence). Following chronic restraint stress in the HR rats, we observed a decrease in the expression of the GRs and GluN2B subunits of the NMDA receptor in the prefrontal cortical areas and the hippocampus compared to the HR-control and the LR-restraint groups. These effects coincided with an increase in passive depressive-like behaviour in the Porsolt test of the HR rats. Moreover, in the hippocampus, the HR-restraint animals demonstrated decreased glutamate levels and a decreased glutamate/glutamine ratio compared to the LR-restraint rats. Furthermore, the HR-restraint group had increased GRs/GluN2B subunits colocalisation in the basolateral amygdala (BLA) compared to the HR-control and the LR-restraint rats. The present results suggest that in HR rats exposed to chronic restraint stress, the hippocampal and cortical glutamatergic system components are changed. These effects could have a negative influence on the feedback mechanisms regulating the hypothalamic-pituitary-adrenal axis as well as on the behavioural processes expressed as depressive-like symptoms.
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