Mood And Anxiety Related Phenotypes In Mice

Affecting approximately twenty percent of the world population, mood and anxiety disorders have been the subject of ever-increasing research. This increased research parallels a remarkable growth in the use of the laboratory mouse as a tool to understand the biological and genetic basis of mood and anxiety disorders as well as to develop improved treatments. In Mood and Anxiety Related Phenotypes in Mice: Characterization Using Behavioral Tests, world-renowned researchers provide an overview of behavioral approaches utilized in the characterization of mood and anxiety related behaviors in mice as well as commonly used behavioral assays to assess the potential antidepressant and anxiolytic efficacy of novel compounds. As a volume in the successful NeuromethodsTM series, the chapters provide authoritative reviews including up-to-date detailed protocols of the most commonly used approaches in the field. Mood and Anxiety Related Phenotypes in Mice: Characterization Using Behavioral Tests is an ideal resource for scientists actively pursuing or interested in establishing behavioral protocols in their laboratories, while also serving as a reference for those students, scientists, and practitioners who have an interest in better understanding the preclinical behavioral methods used in mood and anxiety research.

Preclinical research related to mood and anxiety disorders relies extensively upon mouse behavioral tests and models, the use of which continues to increase as a greater number of underlying susceptibility genes are discovered, new targets for medications are identified, and clinical studies reveal novel neurobiological risk factors. Mood and Anxiety Related Phenotypes in Mice: Characterization Using Behavioral Tests, Volume II serves as a complement to the previous volume in order to offer a comprehensive resource for the behavioral approaches that are valuable for the characterization of mood and anxiety disorder-related behaviors in mice and the techniques that are utilized in the development of effective medications. As a collection presented in the Neuromethods series, each chapter provides a brief background and review of the test or model as well as a complete and up-to-date protocol narrative. Authoritative and comprehensive, Mood and Anxiety Related Phenotypes in Mice: Characterization Using Behavioral Tests, Volume II is an ideal resource for scientists actively pursuing or interested in establishing vital behavioral protocols in their laboratories.

Using the most well-studied behavioral analyses of animal subjects to promote a better understanding of the effects of disease and the effects of new therapeutic treatments on human cognition, Methods of Behavior Analysis in Neuroscience provides a reference manual for molecular and cellular research scientists in both academia and the pharmaceutic

Major Depressive Disorder (MDD) is a debilitating condition that affects 6.7% of American adults and poses a serious public health concern. Meta analyses of clinical studies have identified chronic, low-grade inflammation as a predisposing factor in the development of MDD. Obesity, along with a poor diet, contributes to inflammation, which is especially concerning given the high prevalence of obesity in the United States. Longitudinal studies have established a link between obesity and depression, indicating comorbidity among these two disorders. Unhealthy diets with an excessive caloric content, common in modern Western nations, are a risk factor in the development of obesity and may be the source of obesitys increasing pervasiveness. To better study obesity-induced inflammation in the context of mood disorders, high-fat diet (HFD) treatment provides a reliable method for generating animal models of obesity, particularly using rodents. These HFD models, compared to control diet (CD) treated mice, also display the characteristic phenotypes expected of a model of obesity, including chronic metabolic inflammation and insulin resistance.Neurobiological studies investigating the effects of HFD on the brain have found that rodents treated with HFD exhibit behavioral deficits in anxiety-like behavior, anhedonia, and memory. To further investigate these neurological effects of HFD, and their interactions with genetic and neurophysiological factors, the behavioral consequences of HFD treatment were examined in two different mutant mouse models with an altered ratio of neuronal excitation and inhibition (the E:I ratio). Altered E:I ratio is thought to underlie MDD, and imbalance in the E:I ratio has been shown to produce anxiety- and depression-related behavioral phenotypes in mice. The first model (2+/-) involves mice that are globally heterozygous for the 2 subunit of GABAA receptors. In this model, GABAergic inhibition is reduced, leading to an increased E:I ratio. The 2+/- model has consistently produced an anxious-depressive-like phenotype in behavioral assessments. This phenotype can be diminished by treatment with antidepressants, thus implicating increased E:I ratio in the onset of mood disorders. A second mouse model (SSTCre:2f/f) involves mice in which somatostatin-positive (SST+) interneurons were disinhibited by selectively deleting the 2 subunit of GABAA receptors in these cells. In this model, inhibitory transmission onto hippocampal pyramidal cells was increased by disinhibiting SST+ interneurons, thereby reducing the overall E:I ratio in these mice. Behaviorally, these mice exhibit robust anxiolytic and antidepressant-like phenotypes. Together, results from studies involving 2+/- and SSTCre:2f/f models suggest that an impaired E:I ratio underlies anxiety- and depression-related behavior. The hypothesis examined in the present study, which aims to investigate the interactions between HFD and altered E:I ratio on behavior, is that increasing the E:I ratio (2+/- model) will exacerbate HFD-induced anxiety- and depression-like behavior, including defects in locomotion, grooming, and memory, while reducing the E:I ratio (SSTCre:2f/f model) will reduce HFD-induced anxiety- and depression-like behavior, including defects in locomotion, grooming, and memory. The results show that HFD treatment led to reductions in locomotion and grooming behavior of both the WT control and 2+/- mutant mice in the OFT and SSPT, respectively. However, the effects of HFD on 2+/- mice were not larger than in WT mice, so only an overall diet effect was present. Results from tests assessing short-term working (Y-maze) and recognition (NOR) memory indicate that the effects of diet and genotype are nonadditive, and that HFD treatment and altered E:I ratio impair behavior via different mechanisms. SSTCre:2f/f mutant mice presented an anxiolytic phenotype and increased locomotion in the EPM, consistent with studies in the literature. Additionally, HFD treatment of SSTCre:2f/f mice reduced locomotion in the OFT and EPM, and also decreased grooming behavior in the SSPT. Overall, the behavioral results observed for CD-treated animals in these experiments did not reproduce all of the phenotypes of 2+/- and SSTCre:2f/f mice published in the literature, most likely because the genetic backgrounds of the mice analyzed here (C57BL/6J and mixed 129X1/SvJ/C57BL/6J, respectively) were different from the mice described in earlier studies. Due to these unexpected results, additional behavioral experiments will be needed to further assess possible interactions between HFD treatment and altered E:I balance on anxiety- and depression-related behavior.

This volume looks at classic and novel methods currently used by researchers to understand mood and anxiety disorders and foster precision medicine. Chapters in this book cover topics such as how the sucrose preference succeeds or fails as a measurement of anhedonia; fear conditioning in laboratory rodents; animal models for mania; rodent models for studying the impact of variation in early life mother-infant interactions on mood and anxiety; and prediction of susceptibility/resilience toward animal models of PTSD. In the Neuromethods series style, chapters include the kind of detail and key advice from the specialists needed to get successful results in your laboratory. Comprehensive and cutting-edge, accommodating the novel views on how the neurobiology of psychiatric disorders should be reconceptualized, Psychiatric Vulnerability, Mood, and Anxiety Disorders: Tests and Models in Mice and Rats is a valuable resource for all researchers interested in learning more about this important and developing field.

Scientific advances in our understanding of animal physiology and behavior often require theories to be revised and standards of practice to be updated to improve laboratory animal welfare. This new book from the Institute for Laboratory Animal Research (ILAR) at the National Research Council, Recognition and Alleviation of Distress in Laboratory Animals, focuses on the stress and distress which is experienced by animals when used in laboratory research. This book aims to educate laboratory animal veterinarians; students, researchers, and investigators; animal care staff, as well as animal welfare officers on the current scientific and ethical issues associated with stress and distress in laboratory animals. It evaluates pertinent scientific literature to generate practical and pragmatic guidelines. Recognition and Alleviation of Distress in Laboratory Animals focuses specifically on the scientific understanding of the causes and the functions of stress and distress, the transformation of stress to distress, and the identification of principles for the recognition and alleviation of distress. This book discusses the role of humane endpoints in situations of distress and principles for the minimization of distress in laboratory animals. It also identifies areas in which further scientific investigation is needed to improve laboratory animal welfare in order to adhere to scientific and ethical principles that promote humane care and practice.

The first volume in the new Cambridge Handbooks in Behavioral Genetics series, Behavioral Genetics of the Mouse provides baseline information on normal behaviors, essential in both the design of experiments using genetically modified or pharmacologically treated animals and in the interpretation and analyses of the results obtained. The book offers a comprehensive overview of the genetics of naturally occurring variation in mouse behavior, from perception and spontaneous behaviors such as exploration, aggression, social interactions and motor behaviors, to reinforced behaviors such as the different types of learning. Also included are numerous examples of potential experimental problems, which will aid and guide researchers trying to troubleshoot their own studies. A lasting reference, the thorough and comprehensive reviews offer an easy entrance into the extensive literature in this field, and will prove invaluable to students and specialists alike.

Expanding on the National Research Council's Guide for the Care and Use of Laboratory Animals, this book deals specifically with mammals in neuroscience and behavioral research laboratories. It offers flexible guidelines for the care of these animals, and guidance on adapting these guidelines to various situations without hindering the research process. Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research offers a more in-depth treatment of concerns specific to these disciplines than any previous guide on animal care and use. It treats on such important subjects as: The important role that the researcher and veterinarian play in developing animal protocols. Methods for assessing and ensuring an animal's well-being. General animal-care elements as they apply to neuroscience and behavioral research, and common animal welfare challenges this research can pose. The use of professional judgment and careful interpretation of regulations and guidelines to develop performance standards ensuring animal well-being and high-quality research. Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research treats the development and evaluation of animal-use protocols as a decision-making process, not just a decision. To this end, it presents the most current, in-depth information about the best practices for animal care and use, as they pertain to the intricacies of neuroscience and behavioral research.