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
Steroid hormones regulate gene expression in organisms by binding to receptor proteins. These hormones include the androgens, which signal through androgen receptors (ARs). Endocrine disrupters (EDCs) are chemicals in the environment that adversely affect organisms by binding to nuclear receptors, including ARs. Vinclozolin, a fungicide used on fruit and vegetable crops, is a known anti-androgen, a type of EDC that blocks signals from testosterone and its derivatives. In order to better understand the effects of EDCs, further research on androgen receptors and other hormone signaling pathways is necessary. In this study, we demonstrate the evolutionary conservation between the genomic structure of the human and zebrafish ar genes and find that ar mRNA expression increases in zebrafish embryos exposed to vinclozolin, which may be evolutionarily conserved as well. At 48 and 72 h post-fertilization, vinclozolin-treated embryos express ar mRNA 8-fold higher than the control level. These findings suggest that zebrafish embryos attempt to compensate for the presence of an anti-androgen by increasing the number of androgen receptors available.
Subject(s)
Receptors, Androgen/genetics , Zebrafish Proteins/genetics , Zebrafish/genetics , Animals , Embryo, Nonmammalian/drug effects , Embryo, Nonmammalian/embryology , Embryo, Nonmammalian/metabolism , Female , Fungicides, Industrial/toxicity , Gene Expression Regulation, Developmental/drug effects , Male , Molecular Sequence Data , Oxazoles/toxicity , Phylogeny , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Androgen/classification , Reverse Transcriptase Polymerase Chain Reaction , Up-Regulation/drug effects , Zebrafish/embryologyABSTRACT
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.
