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Introduction Depression has sleep disturbances as a key symptom and recently sleep has been suggested as a new area to optimize treatment in depression. Orexin is produced in the hypothalamus and projected throughout the brain innervating a number of structures important in depression. It controls a number of physiological processes including sleep, arousal, cognitive processes and stress, which are affected during depression. Objective The study examines the possible implications for abnormalities in the orexinergic system in depression. We aim to determine whether treatment targeting this system relieves depressive symptoms. Methods Using real-time qPCR and Western blotting optimal sampling time is determined by an assessment of the diurnal variation of orexin expression. Expression of orexin and its receptors are investigated in the hypothalamus, the hippocampus, and the prefrontal cortex of the Flinders Sensitive Line (FSL) and the Chronic Mild Stress model of depression. Behavioral and molecular response to treatment with a conventional antidepressant and an orexin receptor antagonist will be addressed in FSL rats. In addition, we will include exercise as a noninvasive treatment, which has shown positive effects on both sleep and depression in humans. Results Real-time qPCR analysis showed increased expression of the orexin-1 receptor (40%) and the orexin-2 receptor (39%) in the prefrontal cortex of FSL rats compared to the control rats, the Flinders Resistant Line rats. Conclusion This study may provide a platform for screening of drugs with effects on both sleep and depressive symptoms with perspectives for the development of novel strategies for treatment of depression. [ABSTRACT FROM AUTHOR]

Introduction Rats produce high-frequency sounds (USVs) inaudible to the human ear. When rats are tickled their sound production increases – this is said to reflect positive emotions. The Flinders Sensitive Line (FSL) rat is a genetic rodent model of depression; hence, its altered emotional state may result in a distinct USV profile. Objectives To investigate whether USV profiles differ between rat strains and whether tickling has an antidepressant effect. To examine the effect of ketamine, a presumed rapid-acting antidepressant, on the USV profile. Lastly, to study tickling's effect on genes involved in feeding-regulation in hypothalamus and stress-sensitive genes in the submandibular glands. Aims To explore the utility of USV production during tickling stimulation as a screening method for depressive-like behavior in preclinical research. Methods We investigated the FSL rats’ USVs during six weeks of tickling. Flinders Resistant Line rats, Sprague Dawley rats and a light-touch group were used as controls. Depressive-like behavior was evaluated with the forced swim test. Ketamine or a vehicle was administered acutely after five weeks of tickling. Results Preliminary results show a significant difference between strains in their USV production during tickling. However, data analysis is still in progress and further results will be presented at the congress. Conclusions The study will elucidate the differential development of USVs following tickling stimulation in the FSL, FRL and SD rats, and furthermore shed light on the effect of tickling on the behavioral phenotype and gene expression. [ABSTRACT FROM AUTHOR]

Prenatal stress is believed to increase the risk of developing neuropsychiatric disorders, including major depression. Adverse genetic and environmental impacts during early development, such as glucocorticoid hyper-exposure, can lead to changes in the foetal brain, linked to mental illnesses developed in later life. Dysfunction in the GABAergic inhibitory system is associated with depressive disorders. However, the pathophysiology of GABAergic signalling is poorly understood in mood disorders. Here, we investigated GABAergic neurotransmission in the low birth weight (LBW) rat model of depression. Pregnant rats, exposed to dexamethasone, a synthetic glucocorticoid, during the last week of gestation, yielded LBW offspring showing anxiety- and depressive-like behaviour in adulthood. Patch-clamp recordings from dentate gyrus granule cells in brain slices were used to examine phasic and tonic GABA A receptor-mediated currents. The transcriptional levels of selected genes associated with synaptic vesicle proteins and GABAergic neurotransmission were investigated. The frequency of spontaneous inhibitory postsynaptic currents (sIPSC) was similar in control and LBW rats. Using a paired-pulse protocol to stimulate GABAergic fibres impinging onto granule cells, we found indications of decreased probability of GABA release in LBW rats. However, tonic GABAergic currents and miniature IPSCs, reflecting quantal vesicle release, appeared normal. Additionally, we found elevated expression levels of two presynaptic proteins, Snap-25 and Scamp2 , components of the vesicle release machinery. The results suggest that altered GABA release may be an essential feature in the depressive-like phenotype of LBW rats.

Objectives: Treatment-resistance to antidepressants is a major problem in the pharmacotherapy of major depressive disorder (MDD). Unfortunately, only a few animal models are suitable for studying treatment-resistant depression, among them repeated treatment with Adrenocorticotropic hormone (ACTH) appears to be useful to mimic treatment-resistance to monoaminergic antidepressants. Therefore, the present work aimed to investigate the effectiveness of s-ketamine and rapastinel (formerly GLYX13), modulators of the glutamatergic N-methyl-D-aspartate receptor in ACTH-treated animals., Methods: Naïve male Sprague Dawley rats were subjected to repeated subcutaneous injections with ACTH (100 µg/0.1 ml/rat/day) for 14 days and drug treatment on the test day (open field and forced swim test) with imipramine, s-ketamine or rapastinel. In addition, assessment of plasma levels of corticosterone and ACTH was carried out., Results: We found that rats repeatedly treated with ACTH for 14 days responded to single injections with s-ketamine (15 mg/kg) and rapastinel (10 mg/kg), but failed to respond to imipramine (15 mg/kg). In the plasma, the levels of corticosterone and ACTH were increased after 14 days of daily treatment with ACTH, independently of the treatment., Conclusion: The present data confirm development of a resistance to treatment following chronic ACTH administration. In addition, the study confirms the possible effectiveness of s-ketamine and rapastinel as treatment options in treatment-resistant depression. Moreover, it highlights the importance of the glutamatergic system in the neurobiology of depression. Further studies are necessary to evaluate how repeated treatment with ACTH leads to a depressed condition resistant to monoaminergic antidepressants.

Objective: Psilocybin is a serotonin receptor agonist with a therapeutic potential for treatment-resistant depression and other psychiatric illnesses. We investigated whether the administration of psilocybin had an antidepressant-like effect in a rat model of depression., Methods: Using the Flinders Sensitive Line (FSL) rat model of depression, we assessed the antidepressant-like effect of psilocin and psilocybin, measured as a reduction in immobility time in the forced swim test (FST). We measured locomotor activity in an open field test (OFT) to control for stimulant properties of the drugs. We performed a set of experiments to test different doses, treatment paradigms, and timing of the tests in relation to the drug administration., Results: Psilocin and psilocybin showed no effect on immobility, struggling, or swimming behaviour in the FST and no effect on locomotor activity in the OFT. FSL rats did show significantly more immobility than their control strain, the Flinders Resistant Line, as expected., Conclusion: Psilocin and psilocybin showed no antidepressant-like effect in the FSL rats, despite a positive effect in humans. This suggests that other animal models of depression and other behavioural tests may be more appropriate for translational studies in the effects of psilocybin.

Objective: Gut microbiota (GM) has previously been associated with alterations in rodent behaviour, and since the GM is affected by the diet, the composition of the diet may be an important factor contributing to behavioural changes. Interestingly, a magnesium restricted diet has been shown to induce anxiety and depressive-like behaviour in humans and rodents, and it could be suggested that magnesium deficiency may mediate the effects through an altered GM., Methods: The present study therefore fed C57BL/6 mice with a standard diet or a magnesium deficient diet (MgD) for 6 weeks, followed by behavioural testing in the forced swim test (FST) to evaluate depressive-like behaviour. An intraperitoneal glucose tolerance test (GTT) was performed 2 day after the FST to assess metabolic alterations. Neuroinflammatory markers were analysed from hippocampus. GM composition was analysed and correlated to the behaviour and hippocampal markers., Results: It was found that mice exposed to MgD for 6 weeks were more immobile than control mice in the FST, suggesting an increased depressive-like behaviour. No significant difference was detected in the GTT. GM composition correlated positively with the behaviour of undisturbed C57BL/6 mice, feeding MgD diet altered the microbial composition. The altered GM correlated positively to the hippocampal interleukin-6., Conclusion: In conclusion, we hypothesise that imbalances of the microbiota-gut-brain axis induced by consuming a MgD diet, contributes to the development of depressive-like behaviour.