S40 Behavioural pharmacology 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 open- field 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. Reference(s) [1] Cryan, J.F., Holmes, A., 2005, The ascent of mouse: advances in modelling human depression and anxiety. Nat Rev Drug Discov 4: 775–790. [2] Caldji, C., Francis, D., Sharma, S., Plotsky, P.M., Meaney, M.J., 2000, The effects of early rearing environment on the development of GABAA and central benzodiazepine receptor levels and novelty- induced fearfulness in the rat. Neuropsychopharma- cology 22(3): 219–229. [3] Will, C.C., Aird, F., Redei, E.E., 2003, Selectively bred Wistar-Kyoto rats: an animal model of depression and hyper-responsiveness to antidepressants. Mol Psychiatry. 8(11): 925–932. P.2.09 The source of resting and physiologically- evoked L-glutamate levels in prefrontal cortex in awake rats E.R. Hascup 1 ° , K.N. Hascup 1 , F. Pomerleau 2 , P. Huettl 2 , G.A. Gerhardt 2 , J. Kehr 1 . 1 Karolinska Institute, Physiology & Pharmacology, Stockholm, Sweden; 2 University of Kentucky, Department of Anatomy & Neurobiology Center for Microelectrode Technology Morris K. Udall Parkinson’s Disease Research Center of Excellence, Lexington, USA Purpose: L-glutamate is the major excitatory neuro- transmitter in the mammalian central nervous system and is responsible for maintaining normal brain function such as learning and memory, however, dysregulation of the glutamatergic system is implicated in Alzheimer’s disease, Parkinson’s disease, and schizophrenia. Despite the widespread use of microdialysis in experimental research for measuring L-glutamate levels in the brain, the technique lacks the ability to distinguish between glial- and neuronally-derived pools of extracellular L-glutamate [1]. Thus, microdialysis results have led researchers to hypothesize that extracellular L-glutamate overflow is predominantly derived from astrocytes via the reversal of the high-affinity glutamate transporters [1] or by the cystine-glutamate antiporter. We sought to test the hypothesis that resting L-glutamate levels are predominantly neuronal in origin rather than from astrocytic sources. Using an enzyme-based microelectrode array (MEA) coupled with amperometry, we selectively measured low levels of L-glutamate with a sub-second (500–800 msec) time resolution in the awake rat brain. Methods: Male, Long Evans rats (3–6 months) were used for all experiments. We used self-referencing MEAs, which ensures that the L-glutamate signals are free from endogenous interferents, such as ascorbate [2,3]. MEAs were prepared, calibrated, and chronically im- planted with attached guide cannula in the prefrontal cortex (AP: +3.2 mm; ML: −0.8 mm, DV 5.0 mm vs. bregma) as previously described [2,3]. After an initial acclimation period, we pharmacologically modulated resting L-glutamate levels by locally applying the