P.2.09 The source of resting and physiologically-evoked L-glutamate levels in prefrontal cortex in awake rats

Abstract

the central regulation of stress and anxiety. Wistar Kyoto (WKY) rats are a genetically selected strain which has a marked elevation in anxiety. Previous studies have shown that WKY rats exhibit depressive-like behaviour in a wide range of behavioural paradigms and show reduced responsiveness to some antidepressants when compared to other, less anxious strains (reviewed in [3]). WKY rats also show dysregulation of the HPA axis, with increased basal levels of ACTH and CORT when compared to other rat strains. Whilst it is clear that cortical regions play a role in the integration of the stress response, the relative contribution of various divisions within the cortex to the altered stress responsivity of MS or WKY rats remain unknown. The immediate early gene, c-fos, is rapidly expressed in several brain regions in response to various stressors and is therefore a reliable indicator of activated cell populations in the central nervous system. Following acute exposure to open field (10 min), animals were sacrificed at 2 hours, a time-point which allows for the peak expression of c-fos to be detected. Using c-fos protein immunoreactivity we have compared the response of MS and non-MS Sprague Dawley rats following exposure to an acute psychological (open field) stressor, to analyse their adult behaviour. Defecation rates and behavioural analysis in the openfield were also quantified. The effect of the open field stressor on the WKY rat strain was also assessed to allow a comparison of an environmental and genetic model of depression to be made. Several cortical-limbic structures were analysed for the presence of c-fos positive immunoreactivity including the prelimbic cortex, infralimbic cortex and the rostral and caudal anterior cingulate cortices. These regions of interest were chosen as dysfunctional cortical-limbic structures have been implicated in depression. Our data demonstrate distinct activation patterns within these cortical regions following stress, with significant (p< 0.05) increases in the number of c-fos positive cells found in all regions analysed. These findings suggest an altered cortical activity in these animals that is consistent with that seen in human depressed patients, further supporting their use as animal models of depression. The identification of this neuronal activation pattern may in turn provide further insight into the neurochemical pathways through which therapeutic strategies for depression could be derived.