ABSTRACT
Depression is a common psychiatric disorder, with diverse symptoms and high comorbidity with other brain dysfunctions. Due to this complexity, little is known about the neural and genetic mechanisms involved in depression pathogenesis. In a large proportion of patients, current antidepressant treatments are often ineffective and/or have undesirable side effects, fueling the search for more effective drugs. Animal models mimicking various symptoms of depression are indispensable in studying the biological mechanisms of this disease. Here, we summarize several popular methods for assessing depression-like symptoms in mice, and their utility in screening antidepressant drugs.
Subject(s)
Depressive Disorder/psychology , Animals , Antidepressive Agents , Behavior, Animal , Depressive Disorder/drug therapy , Disease Models, Animal , Humans , Mice , Mice, Inbred Strains , Neuropsychological TestsABSTRACT
Animal models have been vital to recent advances in experimental neuroscience, including the modeling of common human brain disorders such as anxiety, depression, and schizophrenia. As mice express robust anxiety-like behaviors when exposed to stressors (e.g., novelty, bright light, or social confrontation), these phenotypes have clear utility in testing the effects of psychotropic drugs. Of specific interest is the extent to which mouse models can be used for the screening of new anxiolytic drugs and verification of their possible applications in humans. To address this problem, the present chapter will review different experimental models of mouse anxiety and discuss their utility for testing anxiolytic and anxiogenic drugs. Detailed protocols will be provided for these paradigms, and possible confounds will be addressed accordingly.
Subject(s)
Anti-Anxiety Agents/therapeutic use , Anxiety Disorders/psychology , Behavior, Animal/drug effects , Animals , Anti-Anxiety Agents/pharmacology , Anxiety Disorders/drug therapy , Disease Models, Animal , Drug Discovery , Drug Evaluation, Preclinical , Humans , MiceABSTRACT
Depression is a common psychiatric disorder, with diverse symptoms and high comorbidity with other brain dysfunctions. Due to this complexity, little is known about the neural and genetic mechanisms involved in depression pathogenesis. In a large proportion of patients, current antidepressant treatments are often ineffective and/or have undesirable side effects, fueling the search for more effective drugs. Animal models mimicking various symptoms of depression are indispensable in studying the biological mechanisms of this disease. Here, we summarize several popular methods for assessing depression-like symptoms in mice and their utility in screening antidepressant drugs.
Subject(s)
Antidepressive Agents , Behavior, Animal/drug effects , Depressive Disorder , Animals , Antidepressive Agents/adverse effects , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Depressive Disorder/drug therapy , Depressive Disorder/physiopathology , Disease Models, Animal , Grooming/drug effects , Humans , Mice , Mice, Inbred Strains , Neuropsychological Tests , Stress, Physiological , Stress, PsychologicalABSTRACT
Animal models have been vital to recent advances in experimental neuroscience, including the modeling of common human brain disorders such as anxiety, depression, and schizophrenia. As mice express robust anxiety-like behaviors when exposed to stressors (e.g., novelty, bright light, or social confrontation), these phenotypes have clear utility in testing the effects of psychotropic drugs. Of specific interest is the extent to which mouse models can be used for the screening of new anxiolytic drugs and verification of their possible applications in humans. To address this problem, the present chapter will review different experimental models of mouse anxiety and discuss their utility for testing anxiolytic and anxiogenic drugs. Detailed protocols will be provided for these paradigms, and possible confounds will be addressed accordingly.
Subject(s)
Anti-Anxiety Agents , Anxiety , Brain , Drug Discovery , Animals , Anti-Anxiety Agents/pharmacology , Anti-Anxiety Agents/therapeutic use , Anxiety/drug therapy , Anxiety/physiopathology , Behavior, Animal/drug effects , Brain/drug effects , Brain/physiology , Disease Models, Animal , Drug Evaluation, Preclinical , Grooming/drug effects , Humans , Mice , Mice, Inbred Strains , Neuropsychological Tests , Phenotype , Psychotropic Drugs/pharmacology , Psychotropic Drugs/therapeutic use , Stress, PsychologicalABSTRACT
Experimental models are an important tool for the study of biological mechanisms of psychiatric disorders. Although encouraging progress has been made in biological psychiatry of affective disorders, there remain numerous methodological, conceptual, and translational challenges in this field. Mounting clinical data support the view that psychiatric disorders as spectra, rather than as discrete or isolated illnesses. This requires new theories as well as new animal paradigms for "integrative" modeling of psychiatric disorders and their spectra. Here we discuss recent "integrative" experimental models and concepts that promise to advance translational research of affective disorders.
Subject(s)
Disease Models, Animal , Mood Disorders/genetics , Mood Disorders/psychology , Social Environment , Animals , Brain/physiopathology , Epigenesis, Genetic/genetics , Genetic Predisposition to Disease/genetics , Genotype , Humans , Mice , Mice, Knockout , Models, Genetic , Mood Disorders/physiopathology , Phenotype , Rats , ResearchABSTRACT
The zebrafish (Danio rerio) is emerging as a promising model organism for experimental studies of stress and anxiety. Here we further validate zebrafish models of stress by analyzing how environmental and pharmacological manipulations affect their behavioral and physiological phenotypes. Experimental manipulations included exposure to alarm pheromone, chronic exposure to fluoxetine, acute exposure to caffeine, as well as acute and chronic exposure to ethanol. Acute (but not chronic) alarm pheromone and acute caffeine produced robust anxiogenic effects, including reduced exploration, increased erratic movements and freezing behavior in zebrafish tested in the novel tank diving test. In contrast, ethanol and fluoxetine had robust anxiolytic effects, including increased exploration and reduced erratic movements. The behavior of several zebrafish strains was also quantified to ascertain differences in their behavioral profiles, revealing high-anxiety (leopard, albino) and low-anxiety (wild type) strains. We also used LocoScan (CleverSys Inc.) video-tracking tool to quantify anxiety-related behaviors in zebrafish, and dissect anxiety-related phenotypes from locomotor activity. Finally, we developed a simple and effective method of measuring zebrafish physiological stress responses (based on a human salivary cortisol assay), and showed that alterations in whole-body cortisol levels in zebrafish parallel behavioral indices of anxiety. Collectively, our results confirm zebrafish as a valid, reliable, and high-throughput model of stress and affective disorders.