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  • Article: Social fear conditioning as an animal model of social anxiety disorder.
    Iulia Toth, Inga D Neumann, David A Slattery
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    ABSTRACT: Social fear and avoidance of social situations represent the main behavioral symptoms of social anxiety disorder (SAD), a disorder that is poorly elucidated and has rather unsatisfactory therapeutic options. Therefore, animal models are needed to study the underlying etiology of the disorder and possible novel treatment approaches. However, the current paradigms modeling SAD-like symptoms in rodents are not specific, as they induce numerous other behavioral deficits in addition to social fear and avoidance. Here, we describe the protocol for the social fear conditioning paradigm, an animal model of SAD that specifically induces social fear of unfamiliar con-specifics without potentially confounding alterations in other behavioral measures. Theoretical and practical considerations for performing the social fear conditioning paradigm in both rats and mice, as well as for the analysis and interpretation of the obtained data, are described in detail. Curr. Protoc. Neurosci. 63:9.42.1-9.42.13. © 2013 by John Wiley & Sons, Inc.
    Current protocols in neuroscience / editorial board, Jacqueline N. Crawley ... [et al.] 04/2013; Chapter 9:Unit9.42.
  • Article: Sex-dependent regulation of hippocampal neurogenesis under basal and chronic stress conditions in rats.
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    ABSTRACT: Sex differences in basal as well as in stress-induced hippocampal neurogenesis processes have been reported in the literature. However, studies directly comparing sex differences on multiple neurogenesis processes under such conditions are lacking to date. Therefore, the aim of the present study was to directly compare cell proliferation and survival, neuronal and astroglial differentiation as well as stem cells quiescence in male and female Wistar rats under both basal and chronic stress conditions (12 days of 2 h restraint stress (RS)). In addition, corticosterone (CORT) levels and spatial working memory were assessed. Under baseline conditions, only the number of immature neurons within the hippocampal dentate gyrus was higher in males compared with females. In contrast, chronic stress resulted in a number of sex-specific alterations. Thus, stress exposure reduced cell proliferation in males with a concurrent increase in stem cell quiescence, while it did not alter either parameter in females but decreased cell survival. Analysis of astroglial and neuronal differentiation patterns revealed that chronic stress specifically diminished the number of mature neurons in females, with no effect in males. Despite the observed sex differences in adult hippocampal neurogenesis, spatial working memory was not altered by stress exposure in either sex. While basal CORT levels were higher, chronic stress exposure did not affect this parameter in either sex across the initial stress period. This study presents the first direct and detailed evaluation of sex-dependent and chronic stress-induced changes in adult hippocampal neurogenesis not only showing changes in cell proliferation and survival, but moreover immature neuron production, differentiation patterns, stem cell quiescence and therefore contributes to a better understanding of sex differences in neurogenesis processes. © 2013 Wiley Periodicals, Inc.
    Hippocampus 03/2013; · 5.18 Impact Factor
  • Article: Differential effects of baclofen and oxytocin on the increased ethanol consumption following chronic psychosocial stress in mice.
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    ABSTRACT: Chronic stress is known to enhance the susceptibility for addiction disorders including alcoholism. While these findings have been recapitulated in animal models, the majority of these studies have utilized non-social rather than social stress paradigms; the latter of which are believed to be more relevant to the human situation. Therefore, the major aim of this study was to investigate, if 14 days of chronic subordinate colony housing (CSC), a pre-clinically validated psychosocial stress paradigm relevant for human psychiatric and somatic disorders, enhances ethanol (EtOH) consumption in male mice. To assess this, we employed the well-established two-bottle free-choice paradigm where mice were given access to water and 2, 4, 6 and 8% EtOH solutions (with the concentrations increasing each fourth day) following termination of the stress procedure. After 14 days of CSC, stressed mice consumed significantly more EtOH at all concentrations tested and displayed increased EtOH preference at concentrations of 6 and 8%. This effect was not due to an altered taste preference in CSC mice as assessed by saccharine- and quinine-preference tests, but was accompanied by increased anxiety-related behavior. Systemic administration of baclofen (2.5 mg/kg) or oxytocin (OXT; 10 mg/kg) reduced the EtOH intake in single housed control (baclofen, OXT) and CSC (baclofen) mice, whereas intracerebroventricular OXT (0.5 μg/2 μl) was ineffective in both groups. Taken together, these results suggest that (i) chronic psychosocial stress enhances EtOH consumption, and (ii) baclofen and OXT differentially affect EtOH intake in mice.
    Addiction Biology 11/2012; · 4.83 Impact Factor
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    Article: Animal models of depression and anxiety: What do they tell us about human condition?
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    ABSTRACT: While modern neurobiology methods are necessary they are not sufficient to elucidate etiology and pathophysiology of affective disorders and develop new treatments. Achievement of these goals is contingent on applying cutting edge methods on appropriate disease models. In this review, the authors present four rodent models with good face-, construct-, and predictive-validity: the Flinders Sensitive rat line (FSL); the genetically "anxious" High Anxiety-like Behavior (HAB) line; the serotonin transporter knockout 5-HTT(-/-) rat and mouse lines; and the post-traumatic stress disorder (PTSD) model induced by exposure to predator scent, that they have employed to investigate the nature of depression and anxiety.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 12/2010; 35(6):1357-75. · 3.25 Impact Factor
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    Article: Chronic icv oxytocin attenuates the pathological high anxiety state of selectively bred Wistar rats.
    D A Slattery, I D Neumann
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    ABSTRACT: Central oxytocin (OXT) has been shown to promote numerous social behaviours, to attenuate hormonal stress responsiveness of the HPA axis and to decrease anxiety. Wistar rats selectively bred for high (HAB) and low (LAB) anxiety-related behaviour, respectively, have been shown to represent a suitable animal model to study the underlying aetiology of psychopathologies like anxiety- and depression-related disorders. The goal of the present studies was to assess the effects of central OXT on anxiety- and depression-related behaviour in male and female HAB and LAB rats. Acute icv OXT (1 microg) or OXT receptor antagonist (OXT-A; 0.75 microg) administration did not affect anxiety-related behaviour in male or female HAB and LAB rats as assessed in the light-dark box. In contrast, chronic icv OXT infusion (10 ng/h; 6 d) attenuated the high level of anxiety-related behaviour in female, but not male, HAB rats, whereas chronic OXT-A infusion (7.5 ng/h; 6 d) increased anxiety-related behaviour in female, but not male, LAB rats. Neither acute nor chronic manipulation of the OXT system altered depression-related behaviour as assessed by the forced swim test. Combined, these results suggest that pharmacological manipulation of the brain OXT system is effective to attenuate extremes in trait anxiety in an animal model of psychopathological anxiety. Moreover, the data indicate that differences in the activity of the brain OXT systems between HAB and LAB rats may, at least partially, contribute to the opposing anxiety but not depression-related behaviour.
    Neuropharmacology 08/2009; 58(1):56-61. · 4.81 Impact Factor

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