INCREASED SENSITIVITY TO THE EFFECTS OF CHRONIC SOCIAL DEFEAT STRESS IN AN INNATELY ANXIOUS MOUSE STRAIN

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Gut microbiome correlates with altered striatal dopamine receptor expression in a model of compulsive alcohol seeking.

Identifying biological markers predicting vulnerability to develop excessive alcohol consumption may lead to a real improvement of clinical care. With converging evidence suggesting that gut microbiome is capable of influencing brain and behavior, this study aimed at investigating whether changes in gut microbiome composition is associated with conditioned responses to alcohol. We trained Wistar rats to self-administer alcohol for a prolonged period before screening those exhibiting uncontrolled alcohol seeking and taking by modeling diagnostic criteria for AUD: inability to abstain during a signaled period of reward unavailability, increased motivation assessed in a progressive effortful task and persistent alcohol intake despite aversive foot shocks. Based on addiction criteria scores, rats were assigned to either Vulnerable or Resilient groups. Vulnerable rats not only displayed increased impulsive and compulsive behaviors, but also displayed increased relapse after abstinence and increased sensitivity to baclofen treatments compared to resilient animals. Then, rats underwent a 3-month wash out period before sacrifice. Dorsal striatum was collected to assess dopamine receptor mRNA expression, and 16S microbiome sequencing was performed on caecal contents. Multiple significant correlations were found between gut microbiome and impulsivity measures, as well as augmentations in striatal Dopamine 1 receptor (D1R) and reductions in D2R as vulnerability to AUD increased. Therefore, using a singular translational approach based on biobehavioral dispositions to excessive alcohol seeking without heavy intoxication, our observations suggests an association between gut microbiome composition and these specific "at risk" behavioral traits observed in our translationally relevant model

Guidelines for reporting on animal fecal transplantation (GRAFT) studies: recommendations from a systematic review of murine transplantation protocols

Fecal microbiota transplant (FMT) is a powerful tool used to connect changes in gut microbial composition with a variety of disease states and pathologies. While FMT enables potential causal relationships to be identified, the experimental details reported in preclinical FMT protocols are highly inconsistent and/or incomplete. This limitation reflects a current lack of authoritative guidance on reporting standards that would facilitate replication efforts and ultimately reproducible science. We therefore systematically reviewed all FMT protocols used in mouse models with the goal of formulating recommendations on the reporting of preclinical FMT protocols. Search strategies were applied across three databases (PubMed, EMBASE, and Ovid Medline) until June 30, 2020. Data related to donor attributes, stool collection, processing/storage, recipient preparation, administration, and quality control were extracted. A total of 1753 papers were identified, with 241 identified for data extraction and analysis. Of the papers included, 92.5% reported a positive outcome with FMT intervention. However, the vast majority of studies failed to address core methodological aspects including the use of anaerobic conditions (91.7% of papers lacked information), storage (49.4%), homogenization (33.6%), concentration (31.5%), volume (19.9%) and administration route (5.3%). To address these reporting limitations, we developed theGuidelines for Reporting Animal Fecal Transplant (GRAFT) that guide reporting standards for preclinical FMT. The GRAFT recommendations will enable robust reporting of preclinical FMT design, and facilitate high-quality peer review, improving the rigor and translation of knowledge gained through preclinical FMT studies.Kate R. Secombe, Ghanyah H. Al-Qadami, Courtney B. Subramaniam, Joanne M. Bowen, Jacqui Scott, Ysabella Z.A. Van Sebille ... et a

Depression: From Psychopathology to Pharmacotherapy /

Despite the availability of antidepressants for over 40 years, a substantial proportion of depressed patients do not respond adequately to treatment. Failure to respond effectively to treatment contributes to physical ill-health and psychiatric morbidity, often resulting in premature death of the depressed patient. The purpose of this volume is to consider the possible reasons for the limitations of the currently available antidepressants, to examine the advances in our understanding of the psychopathology of depression and how such knowledge may assist in the discovery of new methods of treatment. Leading international experts in this field discuss the possible underlying reasons for depression and limitations of current antidepressants. Opportunities for novel therapeutic approaches to dysfunctional circadian rhythms and mood disorders as well as current status and future perspectives for optimizing antidepressant management of depression are reviewed. This publication illustrates the breadth of the latest research and is valuable reading for psychiatrists, neuroscientists and pharmacologists.What’s new in antidepressant research?Despite the availability of antidepressants for over 40 years, a substantial proportion of depressed patients do not respond adequately to treatment. Failure to respond effectively to treatment contributes to physical ill-health and psychiatric morbidity, often resulting in premature death of the depressed patient. The purpose of this volume is to consider the possible reasons for the limitations of the currently available antidepressants, to examine the advances in our understanding of the psychopathology of depression and how such knowledge may assist in the discovery of new methods of treatment. Leading international experts in this field discuss the possible underlying reasons for depression and limitations of current antidepressants. Opportunities for novel therapeutic approaches to dysfunctional circadian rhythms and mood disorders as well as current status and future perspectives for optimizing antidepressant management of depression are reviewed. This publication illustrates the breadth of the latest research and is valuable reading for psychiatrists, neuroscientists and pharmacologists.Print version recor

Phenotyping of behavioral characteristics.

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Enhancing glutamatergic transmission during adolescence reverses early-life stress-induced deficits in the rewarding effects of cocaine in rats

Item does not contain fulltextAdolescence marks a critical time when the brain is highly susceptible to pathological insult yet also uniquely amenable to therapeutic intervention. It is during adolescence that the onset of the majority of psychiatric disorders, including substance use disorder (SUDs), occurs. It has been well established that stress, particularly during early development, can contribute to the pathological changes which contribute to the development of SUDs. Glutamate as the main excitatory neurotransmitter in the mammalian CNS plays a key role in various physiological processes, including reward function, and in mediating the effects of psychological stress. We hypothesised impairing glutamatergic signalling during the key adolescent period would attenuate early-life stress induced impaired reward function. To test this, we induced early-life stress in male rats using the maternal-separation procedure. During the critical adolescent period (PND25-46) animals were treated with the glutamate transporter activator, riluzole, or the NMDA receptor antagonist, memantine. Adult reward function was assessed using voluntary cocaine intake measured via intravenous self-administration. We found that early-life stress in the form of maternal-separation impaired reward function, reducing the number of successful cocaine-infusions achieved during the intravenous self-administration procedure as well impairing drug-induced reinstatement of cocaine-taking behaviour. Interestingly, riluzole and memantine treatment reversed this stress-induced impairment. These data suggest that reducing glutamatergic signalling may be a viable therapeutic strategy for treating vulnerable individuals at risk of developing SUDs including certain adolescent populations, particularly those which may have experienced trauma during early-life

Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression

The concept that intestinal microbial composition not only affects the health of the gut, but also influences centrally-mediated systems involved in mood, is supported by a growing body of literature. Despite the emergent interest in brain-gut communication and its possible role in the pathogenesis of psychiatric disorders such as depression, particularly subtypes with accompanying gastrointestinal (GI) symptoms, there are few studies dedicated to the search for therapeutic solutions that address both central and peripheral facets of these illnesses. This study aims to assess the potential benefits of the probiotic Bifidobacterium infantis in the rat maternal separation (MS) model, a paradigm that has proven to be of value in the study of stress-related GI and mood disorders. MS adult rat offsprings were chronically treated with bifidobacteria or citalopram and subjected to the forced swim test (FST) to assess motivational state. Cytokine concentrations in stimulated whole blood samples, monoamine levels in the brain, and central and peripheral hypothalamic-pituitary-adrenal (HPA) axis measures were also analysed. MS reduced swim behavior and increased immobility in the FST, decreased noradrenaline (NA) content in the brain, and enhanced peripheral interleukin (IL)-6 release and amygdala corticotrophin-releasing factor mRNA levels. Probiotic treatment resulted in normalization of the immune response, reversal of behavioral deficits, and restoration of basal NA concentrations in the brainstem. 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

Towards a psychobiotic therapy for depression: Bifidobacterium breve CCFM1025 reverses chronic stress-induced depressive symptoms and gut microbial abnormalities in mice

10.1016/j.ynstr.2020.100216Neurobiology of Stress1210021