Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 13 de 13
Filter
Add more filters










Publication year range
1.
Methods Mol Biol ; 1438: 255-69, 2016.
Article in English | MEDLINE | ID: mdl-27150095

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 Tests
2.
Methods Mol Biol ; 1438: 271-91, 2016.
Article in English | MEDLINE | ID: mdl-27150096

ABSTRACT

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 , Mice
3.
BMC Pharmacol ; 11: 3, 2011 Apr 07.
Article in English | MEDLINE | ID: mdl-21473759

ABSTRACT

BACKGROUND: The serotonin 5-HT2C receptor (5-HT2CR) is expressed in amygdala, a region involved in anxiety and fear responses and implicated in the pathogenesis of several psychiatric disorders such as acute anxiety and post traumatic stress disorder. In humans and in rodent models, there is evidence of both anxiogenic and anxiolytic actions of 5-HT2C ligands. In this study, we determined the responsiveness of 5-HT2CR in serotonin transporter (SERT) knockout (-/-) mice, a model characterized by increased anxiety-like and stress-responsive behaviors. RESULTS: In the three-chamber social interaction test, the 5-HT2B/2C agonist mCPP decreased sociability and sniffing in SERT wildtype (+/+) mice, both indicative of the well-documented anxiogenic effect of mCPP. This 5-HT2C-mediated response was absent in SERT-/- mice. Likewise, in the open field test, the selective 5-HT2C agonist RO 60-0175 induced an anxiogenic response in SERT+/+ mice, but not in SERT-/- mice. Since 5-HT2CR pre-mRNA is adenosine-to-inosine (A-to-I) edited, we also evaluated the 5-HT2CR RNA editing profiles of SERT+/+ and SERT-/- mice in amygdala. Compared to SERT+/+ mice, SERT-/- mice showed a decrease in less edited, highly functional 5-HT2C isoforms, and an increase in more edited isoforms with reduced signaling efficiency. CONCLUSIONS: These results indicate that the 5-HT2CR in the amygdala of SERT-/- mice has increased RNA editing, which could explain, at least in part, the decreased behavioral responses to 5-HT2C agonists in SERT-/- mice. These alterations in 5-HT2CR in amygdala may be relevant to humans with SERT polymorphisms that alter SERT expression, function, and emotional behaviors.


Subject(s)
Amygdala/physiology , RNA Editing , Receptor, Serotonin, 5-HT2C/physiology , Serotonin 5-HT2 Receptor Agonists/pharmacology , Serotonin Plasma Membrane Transport Proteins/deficiency , Amygdala/metabolism , Animals , Anxiety/chemically induced , Anxiety/genetics , Anxiety/metabolism , Behavior, Animal/drug effects , Ethylamines/pharmacology , Indoles/pharmacology , Interpersonal Relations , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Piperazines/pharmacology , RNA Precursors/genetics , RNA Precursors/metabolism , Receptor, Serotonin, 5-HT2C/genetics , Receptor, Serotonin, 5-HT2C/metabolism , Serotonin Plasma Membrane Transport Proteins/genetics , Serotonin Plasma Membrane Transport Proteins/metabolism
4.
Psychopharmacology (Berl) ; 212(1): 13-23, 2010 Sep.
Article in English | MEDLINE | ID: mdl-19823806

ABSTRACT

RATIONALE: There are few reports on the high-affinity 5-HT(2A) agonist (4-Bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine hydrobromide (TCB-2). OBJECTIVES: Here we provide the first behavioral and neurophysiological profile of TCB-2 in C57BL/6J mice, with direct comparisons to the 5-HT(2A/2C) agonist (+/-)-2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), in addition to determinations of 5-HT(2A) mediation via pretreatment with the selective 5-HT(2A) antagonist MDL 11,939. RESULTS: In a dose-dependent manner, TCB-2 induced head twitches, decreased food consumption in food-deprived mice, induced hypothermia, and increased corticosterone levels, with no effects on locomotor activity or anxiety-like behaviors in the open field. Similar effects were observed in side-by-side dose-response comparisons with DOI; although at the highest dose tested (5.0 mg/kg), TCB-2 induced significantly fewer head twitches, and a significantly enhanced hypothermic response, versus DOI. Pretreatment with MDL 11,939 blocked head twitches and temperature change following TCB-2 and DOI, confirming 5-HT(2A) mediation of these responses. Although MDL 11,939 pretreatment blocked DOI-induced suppression of feeding, MDL 11,939 had no effect on TCB-2-induced suppression of feeding. Previous studies show that 5-HT(2A) function is altered by changes in serotonin transporter (SERT) expression and function. In SERT knockout (-/-) mice, TCB-2-induced head twitches and hypothermia were greatly diminished compared to SERT wild-type (+/+) mice. CONCLUSIONS: The current studies are important, as they are the first to assess the effects of TCB-2 in mice, and are among the first to report the behavioral and neurophysiological effects of this conformationally restricted phenethylamine analog compound, which has 65-fold greater effects on signaling via the phosphoinositide versus arachidonic acid pathways.


Subject(s)
Bridged Bicyclo Compounds/pharmacology , Methylamines/pharmacology , Serotonin 5-HT2 Receptor Agonists , Serotonin Plasma Membrane Transport Proteins/genetics , Serotonin Receptor Agonists/pharmacology , Animals , Arachidonic Acid/metabolism , Behavior, Animal/drug effects , Bridged Bicyclo Compounds/administration & dosage , Dose-Response Relationship, Drug , Head Movements/drug effects , Hypothermia/chemically induced , Male , Methylamines/administration & dosage , Mice , Mice, Inbred C57BL , Mice, Knockout , Phosphatidylinositols/metabolism , Serotonin Receptor Agonists/administration & dosage
5.
Methods Mol Biol ; 602: 267-82, 2010.
Article in English | MEDLINE | ID: mdl-20012404

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)
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, Psychological
6.
Methods Mol Biol ; 602: 299-321, 2010.
Article in English | MEDLINE | ID: mdl-20012406

ABSTRACT

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, Psychological
7.
J Affect Disord ; 121(1-2): 1-9, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19428115

ABSTRACT

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 , Research
8.
Behav Pharmacol ; 19(5-6): 377-84, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18690099

ABSTRACT

Investigating the pathogenesis of psychiatric disorders is a complicated and rigorous task for psychiatric geneticists, as the disorders often involve combinations of genetic, behavioral, personality, and environmental factors. To nurture further progress in this field, a new set of conceptual tools is needed in addition to the currently accepted approaches. Concepts that consider cross-species trait genetics and the interplay between the domains of disorders, as well as the full spectrum of potential symptoms and their place along the pathogenetic continuum, are particularly important to address these needs. Here, we outline recent concepts and approaches that can help refine the field and enable more precise dissection of the genetic mechanisms contributing to psychiatric disorders.


Subject(s)
Disease Models, Animal , Mental Disorders/genetics , Animals , Biological Evolution , Brain Diseases/genetics , Epigenesis, Genetic/genetics , Genetic Predisposition to Disease/genetics , Genotype , Humans , Mice , Phenotype , Social Environment , Species Specificity
9.
Behav Brain Res ; 188(2): 243-9, 2008 Apr 09.
Article in English | MEDLINE | ID: mdl-18164476

ABSTRACT

Genetic and environmental factors play a key role in psychiatric disorders. While some disorders display exceptionally high heritability, others show gene x experience x personality interactions, contributing complexity to psychiatric phenotypes. As some brain disorders frequently overlap and co-occur (representing a continuum or spectrum of phenomena), modern psychiatry is shifting from "artificial" heterogeneity to the recognition of common elements in the pathogenesis of emotional, personality and behavioral disorders. Genetic animal models of these disorders represent an important direction of research, and are widely used to explore the role of different genes in brain mechanisms. Several concepts (such as endophenotypes, gene x environment interactions, and cross-species trait genetics) have been suggested for animal experimentation in this field. Here we develop a new concept based on targeting the complex interplay between different behavioral domains, meant to foster high-throughput phenotyping and integrative modeling of psychiatric disorders.


Subject(s)
Disease Models, Animal , Genetic Predisposition to Disease/genetics , Mental Disorders/genetics , Mental Disorders/physiopathology , Phenotype , Animals , Behavior, Animal , Humans
10.
Nat Protoc ; 3(1): 129-36, 2008.
Article in English | MEDLINE | ID: mdl-18193029

ABSTRACT

Animal behavioral models are crucial for neurobiological research, allowing for the thorough investigation of brain pathogenesis to be performed. In both animals and humans, anxiety has long been linked to vestibular disorders. However, although there are many tests of anxiety and vestibular deficits, there are few protocols that address the interplay between these two domains. The Suok test and its light-dark modification presented here appear to be suitable for testing this pathogenetic link in laboratory rodents. This protocol adds a new dimension to previously used tests by assessing animal anxiety and balancing simultaneously, resulting in efficient, high-throughput screens for testing psychotropic drugs, phenotyping genetically modified animals, and modeling clusters of human disorders related to stress/anxiety and balancing.


Subject(s)
Anxiety , Behavior, Animal , Behavioral Research/methods , Light , Psychomotor Performance , Acclimatization , Animals , Behavioral Research/instrumentation , Darkness , Mice , Models, Animal , Postural Balance , Rats
11.
Prog Neuropsychopharmacol Biol Psychiatry ; 32(5): 1172-8, 2008 Jul 01.
Article in English | MEDLINE | ID: mdl-18222590

ABSTRACT

The use of batteries of single-domain tests for neurophenotyping research is a common strategy to achieve higher data density and explore different behavioral domains. This approach, however, is accompanied by several methodological challenges, briefly discussed here. As an alternative, this paper advocates the wider use of extensive "hybrid" protocols that assess multiple domains in parallel, or logically/logistically combine experimental paradigms, in a way that disproportionately maximizes the number of tested phenotypes per experimental manipulation. Several examples of this approach are given in this paper, demonstrating the potential to reduce time, cost and subject requirements for the experiments. Offering behavioral analyses that are lacking in the standard single-domain tests, such "hybrid" models enable innovative modeling of neuropsychiatric disorders by more thorough and broader investigation of complex phenotypical characteristics.


Subject(s)
Disease Models, Animal , Pharmaceutical Solutions , Phenotype , Research Design , Animal Testing Alternatives/methods , Animals , Behavior/drug effects , Behavior, Animal , Humans , Information Services
12.
Neurochem Int ; 52(4-5): 649-58, 2008.
Article in English | MEDLINE | ID: mdl-17935833

ABSTRACT

Serotonin syndrome, or serotonin toxicity, is a serious disorder attributable to exaggerated serotonergic function in the brain, most commonly after antidepressant overdose or after combining several psychotropic medications. Similar condition (serotonin syndrome-like behavior) can be evoked in animals experimentally, following administration of serotonergic drugs. In addition to pharmacological stimulation, some genetic and other factors may contribute to serotonin toxicity, prompting the need for new experimental genetic models relevant to this disorder. Here we discuss current problems and perspectives regarding genetic animal models of serotonin-related syndromes, and outline the potential utility of these models in experimental neurochemistry and clinical research.


Subject(s)
Serotonin Syndrome/genetics , Serotonin Syndrome/physiopathology , Serotonin/toxicity , Animals , Disease Models, Animal , Humans , Mice , Mice, Mutant Strains , Mice, Transgenic , Rats
13.
Nat Protoc ; 2(10): 2538-44, 2007.
Article in English | MEDLINE | ID: mdl-17947996

ABSTRACT

Grooming is a commonplace, robust behavior in rodent species. It has been shown to be highly sensitive to a number of experimental factors, making it an ideal target for manipulation. The complex patterning of grooming in rodents, which usually proceeds in a cephalo-caudal direction and involves several distinct stages, can be dissected into its constituent parts and microstructures. Several grooming patterning analysis methods are described in the protocol that allow for an assessment of this behavior based on measurements of grooming activity and its sequencing. Additionally, grooming can be evaluated in reference to the regional distribution and syntax in which it occurs. Owing to the ever-increasing number of rodent models that have strong grooming phenotypes, this high-throughput in-depth analysis is becoming crucial for biomedical research.


Subject(s)
Behavioral Research/methods , Grooming , Mice , 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology , Acclimatization , Algorithms , Animals , Dopamine Agonists/pharmacology , Grooming/drug effects , Quinpirole/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL
...