J F Cryan

..This review focuses on the attempts to improve current paradigms and also illustrates examples where current paradigms are used to uncover novel molecular targets of antidepressants...

..These data suggest that acute knockdown of APP in adult mouse brain impairs hippocampus-dependent spatial working memory...

..Thus, the emerging concept of a microbiota-gut-brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders...

..In this study, we investigated tryptophan degradation in a male IBS cohort (n = 10) and control subjects (n = 26)...

..Such tailoring of tools that deliver RNAi in the brain will significantly aid in our understanding of the complex pathophysiology of neuropsychiatric disorders where there is an immensely unmet medical need...

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..It is clear that a better alignment of the interactions between basic and clinical scientists is needed if this is to change...

..Thus we assessed the impact of a selective 5-HT(2B) receptor antagonist, RS-127445, on visceral hypersensitivity in a model of brain gut axis dysfunction the Wistar Kyoto (WKY) rat...

..Moreover, they suggest that glial physiology may become a therapeutic target in depression and other stress-related conditions...

..CONCLUSIONS & INFERENCES This study demonstrates that psychological and physical stressors alter colonic CRF receptor expression and further support a role for local colonic CRF signalling in stress-induced changes in GI function...

..In this study, we evaluated the efficacy of repeated treatment with three different probiotics in reducing visceral pain in visceral normosensitive (Sprague-Dawley [SD]) and visceral hypersensitive (Wistar-Kyoto [WKY]) rat strains...

..These data demonstrate that specific alterations in TLR agonist-mediated cytokine release contribute to the evidence of immune dysfunction in psychotic disorders...

..The withdrawal, due to adverse events, of a number of pharmacological agents that were approved for the treatment of IBS has left a therapeutic vacuum for patients suffering from the disorder...

..While B. breve 6330 influenced BDNF in normal animals, it had no significant effect on BDNF in those which were maternally separated. We have demonstrated that an orally administered probiotic can influence hippocampal BDNF...

..Moreover, these results illustrate the strong influence of dietary components on stress-induced psychological factors and thereby emphasize the importance of the brain-gut-axis as a point of future therapeutic intervention...

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..This makes the identification of the neurobiological substrates that are affected by adverse experiences in early life invaluable...

..Our results identify a proinflammatory PUFA profile as a persistent consequence of early-life stress and suggest new avenues of investigation in stress-related disorders...

..In this study we examined the hypothesis that the antidepressant-like effects of verapamil are mediated through its blockade of the Pgp transporter in the blood brain barrier (BBB)...

..The successful identification of biomarkers is critical to progressing our understanding of IBS and addressing the unmet therapeutic needs of this debilitating condition...

..Together, our data identifies a novel proinflammatory mechanism in irritable bowel syndrome and also suggests that elevated arachidonic acid levels in plasma may serve as putative biological markers in this condition...

..Accumulating evidence suggest that stress, especially in early life, is a predisposing factor to IBS...

..This study demonstrates that acute stressors alter colonic CRF receptor expression in a manner that is determined by the underlying stress sensitivity of the subject...

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..Therefore, the present study aimed to investigate the effect of P-gp inhibition on the transport of the tricyclic antidepressant imipramine and its active metabolite desipramine across the BBB...

..These findings point to a more influential role for bifidobacteria in neural function, and suggest that probiotics may have broader therapeutic applications than previously considered...

..The immune system is a critical regulator of the brain-gut axis. Toll-like receptors (TLRs) are pattern recognition molecules regulating innate immunity...

..This study provides evidence of altered colonic function and morphology in two animal models with a heightened response to stress...

..Moreover, since BALB/cOLaHsd mice respond to lithium plus desipramine but not to either drug alone, they may become useful in the development of a mouse model of treatment-refractory depression for which there is an unmet need...

..These data indicate altered central mRNA expression of tryptophan metabolising enzymes and immune activation in BALB/c mice compared to the normo-sensitive C57BL/6J strain...

..These data suggest different coping strategies to social interaction stress between the two mouse strains. The genetic basis of this stress-resilience/susceptibility warrants further investigation...

..This present study investigated the expression and possible functional role of mGlu(7) receptors in the mouse colon...

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..Because alterations in spinal non-neuronal (astrocytic) glutamate reuptake are suspected to participate in chronic pain, we asked whether such processes occur in visceral hypersensitivity...

..Therefore, while further research is necessary, it is suggested that GABA(B) receptor antagonists may represent a new class of antidepressant compounds...

..It was our hypothesis that innate immune receptor expression may be changed in the gastrointestinal tract of animals with stress-induced IBS-like symptoms...

..The lower levels of stress-induced activity in high anxiety BALB/c mice, possibly indicate a circuit dysregulation at the cortico-limbic level in response to stress...

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..This review summarizes the new potential roles of mGlu receptors and raises the possibility of novel pharmacological targets for various disorders...

..Leptin, encoded by the ob gene, plays an important part in the energy homeostasis and is critical for the development of obesity...

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..Taken together, we conclude that the tail suspension test is a useful test for assessing the behavioural effects of antidepressant compounds and other pharmacological and genetic manipulations relevant to depression...

..Application of this nonviral RNAi approach may accelerate target validation for neuropsychiatric disorders that involve a complex interplay of gene(s) from various brain regions...

..Application of this non-viral RNAi approach may accelerate target validation for neuropsychiatric disorders that involve a complex interplay of gene(s) from various brain regions...

..Recent findings indicate specific roles for these isoforms in conditioned fear responses, although their influence on behavior in tests of unconditioned anxiety is unknown...

..It is therefore possible that functional GABAB receptors exist in neurons that naturally lack GABAB(2) subunits...

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..e., elevations in brain reward thresholds) and behaviors opposite to those seen after treatment with antidepressant drugs, such as decreased immobility in the forced swim test and the tail suspension test...

..Therefore, drugs acting at mGluR7 may provide novel treatments for psychiatric disorders such as depression and anxiety...

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..Deficits in reward function, which underlie anhedonia, can be readily assessed in animals. Therefore, anhedonia may serve as an endophenotype for understanding the neural circuitry and molecular pathways underlying depression...

..Taken together, these data suggest that forebrain regions innervated by these two distinct noradrenergic pathways exert opposing influences on the behavioral response to reboxetine in the rat forced swim test...

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..These data show that NE plays an important role in mediating acute behavioral and neurochemical actions of many antidepressants, including most SSRIs...

..Together, these data demonstrate that GABA(B) receptor antagonists via an interaction with the serotonergic system display antidepressant-like properties and therefore represent a novel approach for the treatment of depression...

..Finally, a physiological model of performance in the rat FST has been proposed involving the regulation of 5-HT transmission by corticotropin releasing factor (CRF)...

..This suggests that modifications of the FST can be used to examine the onset of action of antidepressant agents produced by long-term administration...

..Here, we assess the current status of research into developing appropriate tests for assessing such behaviours...

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..We conclude that genetic ablation of mGluR7 in mice interferes at multiple sites in the neuronal circuitry and molecular pathways implicated in affective disorders...

..The constitutive absence of GABAB1a but not GABAB1b results in impaired synaptic plasticity and hippocampus-dependent memory, emphasizing molecular differences in synaptic GABAB functions...

..These include mice that lack functional GABA(B) receptors, and novel positive modulators of the GABA(B) receptor. In this review, we discuss evidence that points to a role of GABA(B) receptors in anxiety and depression...

..Further investigation of GABA(B) receptor-positive modulation as a novel therapeutic strategy for the treatment of cocaine dependence and possibly other drugs of abuse is therefore warranted...

..It appears to depend on glutamatergic and higher-level brain functions similar to those involved in spatial working memory but functionally dissociated from those that mediate constitutional responses in anxiety tests...

..Activation of one or more of the serotonin (5-HT) receptors may play a role in mediating the antidepressant effects of SSRIs...