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Background: Depression has been associated with a low-grade inflammation and immune activation, as revealed by clinical studies showing elevated levels of pro-inflammatory cytokines and acute phase proteins in depressed patients. These patients are often treatment-resistant, and some studies show that elevated markers of inflammation predict a poor response to treatment. Furthermore, increasing evidences show that metabolic abnormalities such as obesity and diabetes mellitus type 2 are associated with a low-grade inflammation. Objectives: The aim of this study is to investigate the effects of a systemic low-grade inflammation induced by lipopolysaccharide (LPS) on adult Sprague-Dawley rats on depression-like and metabolic parameters. Methods: Chronic infusion of LPS (at a high, medium and low dose) for 28 days was performed by using subcutaneously implanted osmotic minipumps (Alzet(registered trademark) 2ML4, infusion rate 2.5l/day), which delivers LPS through a catheter into the abdomen. Depression-like behavior was assessed as increased time spent immobile in the forced swim test (FST). Peripheral markers of a low-grade inflammation was measured using a high sensitivity ELISA kit and central levels of pro-inflammatory cytokines (TNF-alpha, IL-1, IL-6) together with the expression of enzymes involved in the tryptophan-kynurenine pathway, will be analyzed in specific brain regions using real-time qPCR. Body weight and food intake was measured once a week, while fasting glucose and insulin sensitivity was assessed after four weeks of LPS administration. Findings and conclusion: Our results showed that a low dose of LPS increased immobility in the FST relative to vehicle treatment, indicative of depression-like behavior. We did not find any difference in body weight, fasting glucose and insulin values. However, a high dose of LPS caused an increase in liver weight. Analysis of cytokine and mRNA expression levels is currently being carried out and these results are pending. Our preliminary results indicate that a low dose of LPS can produce depression-like behavior, without inducing metabolic disturbances or sickness behavior. Thus, this model might help elucidating some of the mechanisms underlying inflammation-associated depression, in order to assist in developing more effective treatment strategies for this group of patients.

Background and Aim: Stress-induced excessive glutamate transmission at N-methyl-D-aspartate (NMDA) receptors may underlie a major mechanism in the pathophysiology that leads to depression, while ketamine, an NMDA receptor antagonist, has been shown to induce a rapid antidepressant effect in depressed patients following a single intravenous administration that is sustained for (plus or minus) 7 days. A number of downstream cellular mechanisms appear to mediate the antidepressant action of ketamine, and the majority of evidence point to a rapid activation of protein translation leading to increased synaptic protein synthesis in the frontal cortex as vital processes that underlie its antidepressant action. However, the upstream mechanism(s) that are affected, i.e. immediately downstream of NMDA receptors, remain unclear. Neuronal nitric oxide synthase (nNOS) is directly coupled to and activated by NMDA receptors, while the uncoupling of the nNOS-NMDA receptor complex prevents NMDA-induced excitotoxicity. Thus, it is possible that the inhibition of nitric oxide (NO) signalling underlies a key upstream mechanism in the antidepressant action of ketamine. Methods: We used a genetic rat model of depression, the Flinders Sensitive Line (FSL) rats, which present with increased depression-like behaviour and abnormalities in NO signalling and synaptic protein regulation, compared to their control, the Flinders Resistant Line (FRL) rats to test our hypothesis. Specifically, we investigated whether l-arginine, a precursor and a stimulant of NO production can attenuate behavioural and cellular antidepressant-like effects induced by ketamine. Four groups of FSL rats received vehicle (saline, i.p.), ketamine (15 mg/kg, i.p.), l-arginine (250 mg/kg, i.p.) or a combination of ketamine and l-arginine, and assessed in the FST 1 hour later, whereafter the frontal cortex regions were dissected for the measurement of nNOS activity and synaptic proteins (i.e. GluR1, GluR2, NR2A/B, NR1 and PSD-95) using western blotting. A vehicle-treated group of FRL rats was included as behavioural validation and to characterise the FSL/FRL model in more detail with regard to the regulation of these proteins. Results: The behavioural data from the FST showed that l-arginine significantly attenuated the antidepressant-like action of ketamine, suggesting that ketamine may indeed exert its antidepressant action by reducing NO signalling. However, molecular experiments that may shed more light on this mechanism are currently in progress and we expect these results to be available soon.

Mathematical programming and computers have been used for several decades to solve complex and long term forest management planning problems. The ever increasing demand on the forest ecosystem to produce wood and other goods and services poses a corresponding demand on a forest decision support system. As a response to meet new requirements the development of the Heureka system was initiated at SLU in 2002 and a first version of the system was released in 2009. Based on a common kernel, a number or applications of the system for different problem areas and users have been developed. The three main applications are made up by an interactive stand simulator, a tool for long term forest level planning containing an optimization module, and a simulator for regional analyses. The system contains models for growth projections, simulation of treatments, estimation of recreation values and carbon sequestration, and habitat suitability. It is also possible to make projections under different climate scenarios. In addition the system includes a number of supporting applications for importing data from different sources, for field inventory, and for comparing and ranking alternative management plans.

Background: Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behavior in rodents. However, little knowledge is available to what extent the NPS system is involved in depression-related behaviors. The aim of the present work was to characterize the effects of centrally administered NPS on depression- and anxiety-related behaviors, using a well validated animal model of depression, the Flinders Sensitive Line (FSL) rats and their controls the Flinders Resistant Line (FRL). Methods: Male and female were tested. Seven days following insertion of cannula, 0.25 or 1.0 nmol NPS, or vehicle/5 ml were infused into the lateral ventricle. 45 min after NPS infusion animals were tested on elevated plus maze (EPM). Five days later the animals were subjected to the two-day forced swim test (FST); NPS or vehicle were injected 45 min before the second day FST. In selected animals effect of NPS on home cage activity was explored. Finally, brains from separate groups of naive animals were harvested; hippocampi, amygdalae and PVN punched out, and mRNA transcripts measured with the real-time quantitative polymerase chain reaction (rt-qPCR). Results: The most salient findings were: (1) NPS increased in a dosedependent fashion the percent time spent in the open arms and the number of full entries in the FSL rat (p'so0.01), while the effects in the FRL were only marginal; (2) In contrast to altered behavior in the EPM, behavior in the FST was not affected by NPS; (3) In the home cage, NPS increased locomotion in a dose dependent fashion in the FSL; (4) rt-qPCR showed that NPSR expression was lower in amygdalae in the FSL; no other region or strain differences were found. Discussion: Baseline depression-like behavior was markedly higher in the FSL compared to FRL rats while no difference in the anxiety-like behavior was observed. These findings confirm the utility of the FSL as a model of depression useful in exploration of neurobiological correlates both of depression and those discriminating between depression and anxiety endophenotypes. NPS had marked anxiolytic effects but did not modify the depression-like behavior. These results clearly separate effects of NPS from those of the classical antidepressants (tricyclics and SSRIs) which are also anxiolytic, and indicate that NPS agonists could be useful as selective anxiolytic drugs.

When developing ligands for emission tomography studies, one of the major obstacles lies in the selection of ligand candidates. A previously unattended factor such as the influence of temperature on candidate ligand affinity is likely to play a role. By use of rat brain homogenates, the binding characteristics of [(3)H]-(S)-citalopram and [(3)H]-(+)-McN5652 and the receptor-ligand interaction at the serotonin transporter of 17 selective serotonin reuptake inhibitors were compared at 21 degrees C and 37 degrees C, respectively. Ligand logP values were also calculated. The ratios for K(i) at 37 degrees C vs. 21 degrees C varied between 0.2 and 2.2 for the selective serotonin reuptake inhibitors considered in this study, with most of the ligands displaying an inverse relationship between K(i) and temperature. Ten of the 17 selective serotonin reuptake inhibitors were found to have pK(i) values statistically significantly different at 21 degrees C compared to 37 degrees C (P < 0.05). The logP values ranged between 3.6 and 4.8, except for DASB, 5-iodo-6-nitroquipazine, and paroxetine where logP was 1.9, 2.2, and 5.0, respectively. K(d) was 0.71 nM at 37 degrees C and 0.31 nM at 21 degrees C for [(3)H]-(S)-citalopram. For [(3)H]-(+)-McN5652 K(d) was 0.11 nM at 37 degrees C and 0.08 nM at 21 degrees C. The association and dissociation was much faster for [(3)H]-(S)-citalopram as compared to [(3)H]-(+)-McN5652. It is concluded that temperature may affect K(d) differently and that in vitro dissociation may help to predict whether a given ligand may be useful in PET studies. LogP values do not per se predict the potential of a given ligand as an emission tomography tracer.