Animal Models and Assays Probing Anxiety Related Behaviors and Neural Circuits

2017 ◽  
Author(s):  
Ramon Tasan ◽  
Nicolas Singewald
Keyword(s):  
Animal Models ◽  
Anxiety Disorders ◽  
Predictive Value ◽  
Selective Breeding ◽  
Neural Circuits ◽  
Neural Pathways ◽  
Novel Treatment ◽  
Conditioned Learning ◽  
Approach Avoidance ◽  
Pathological Anxiety

Anxiety tests and models in rodents are useful tools to reveal neurochemical, cellular, and molecular underpinnings of normal and pathological anxiety-related behaviors, as well as novel treatment targets. While anxiety models are generated by various approaches such as selective breeding, anxiety tests most commonly involve unconditioned approach avoidance tasks and conditioned learning paradigms, both characterized by inherent advantages and limitations, in particular their predictive value for specific anxiety disorders. To further improve the validity and translatability of preclinical anxiety testing, it is promising that some anxiety-relevant endophenotypes have now been investigated using similar tests in rodents and humans and that the involved neural pathways and mechanisms overlap considerably in both species.

scholarly journals Fronto-striatal projections regulate approach-avoidance conflict

2020 ◽  
Author(s):  
Adrienne C. Loewke ◽  
Adelaide R. Minerva ◽  
Alexandra B. Nelson ◽  
Anatol C. Kreitzer ◽  
Lisa A. Gunaydin
Keyword(s):  
Anxiety Disorders ◽  
Avoidance Behavior ◽  
D1 Receptor ◽  
Projection Neurons ◽  
Medium Spiny Neurons ◽  
Neural Pathways ◽  
Spiny Neurons ◽  
Striatal Projection Neurons ◽  
Neural Computations ◽  
Approach Avoidance

ABSTRACTThe dorsomedial prefrontal cortex (dmPFC) has been linked to approach-avoidance behavior and decision-making under conflict, key neural computations thought to be altered in anxiety disorders. However, the heterogeneity of efferent prefrontal projections has obscured identification of the specific top-down neural pathways regulating these anxiety-related behaviors. While the dmPFC-amygdala circuit has long been implicated in controlling reflexive fear responses, recent work suggests that this circuit is less important for avoidance behavior. We hypothesized that dmPFC neurons projecting to the dorsomedial striatum (DMS) represent a subset of prefrontal neurons that robustly encode and drive approach-avoidance behavior. Using fiber photometry recording during the elevated zero maze (EZM) task, we show heightened neural activity in prefrontal and fronto-striatal projection neurons, but not fronto-amydalar projection neurons, during exploration of the anxiogenic open arms of the maze. Additionally, through pathway-specific optogenetics we demonstrate that this fronto-striatal projection preferentially excites postsynaptic D1 receptor-expressing medium spiny neurons in the DMS and bidirectionally controls avoidance behavior. We conclude that this striatal-projecting subpopulation of prefrontal neurons regulates approach-avoidance conflict, supporting a model for prefrontal control of defensive behavior in which the dmPFC-amygdala projection controls reflexive fear behavior and the dmPFC-striatum projection controls anxious avoidance behavior. Our findings identify this fronto-striatal circuit as a valuable therapeutic target for developing interventions to alleviate excessive avoidance behavior in anxiety disorders.

scholarly journals Experimental animal models for the simulation of depression and anxiety

2006 ◽  
Vol 8 (3) ◽  
pp. 323-333 ◽  
Keyword(s):  
Animal Models ◽  
Anxiety Disorders ◽  
Experimental Models ◽  
Depression And Anxiety ◽  
Human Situation ◽  
Clinical Syndromes ◽  
Behavioral Parameters ◽  
The Relationship ◽  
Psychiatric Problems ◽  
Pathological Anxiety

An impressive number of animal models to assess depression and anxiety are available today. However, the relationship between these models and the clinical syndromes of depression and anxiety is not always clear. Since human anxiety disorders represent a multifactorial phenomenon frequently comorbid with major depression and/or other psychiatric problems, the chance of creating animal models which consistently reflect the human situation is quite poor. When using experimental models to understand homologies between animal and human behavior, we have to consider the context in which an animal is investigated, and both the functional significance and relevance of the behavioral parameters that are quantified. Moreover, gender and interindividual and interspecies variabilities in behavioral responses to the test situation and in the sensitivity to pharmacological treatments are potential sources for confounding results. In the past, these aspects have been often neglected in preclinical approaches to behavioral pharmacology and psychopharmacology. A pragmatic approach of combined preclinical and clinical efforts is necessary to imitate one or more aspects relevant to pathological anxiety disorders and depression. The resulting models may identify central nervous processes regulating defined behavioral output, with the potential to develop more effective treatments.

A review on aversive Pavlovian-to-Instrumental transfer in humans

2020 ◽  
Author(s):  
Anna Gerlicher ◽  
Merel Kindt
Keyword(s):  
Avoidance Behavior ◽  
Neural Circuits ◽  
Transfer Effects ◽  
Future Directions ◽  
Transfer Paradigm ◽  
Wide Range ◽  
Threat Cues ◽  
Imminent Threat ◽  
Fear And Anxiety ◽  
Pathological Anxiety

A cue that indicates imminent threat elicits a wide range of physiological, hormonal, autonomic, cognitive, and emotional fear responses in humans and facilitates threat-specific avoidance behavior. The occurrence of a threat cue can, however, also have general motivational effects and affect behavior. That is, the encounter with a threat cue can increase our tendency to engage in general avoidance behavior that does neither terminate nor prevent the threat-cue or the threat itself. Furthermore, the encounter with a threat-cue can substantially reduce our likelihood to engage in behavior that leads to rewarding outcomes. Such general motivational effects of threat-cues on behavior can be informative about the transition from normal to pathological anxiety and could also explain the development of comorbid disorders, such as depression and substance abuse. Despite the unmistakable relevance of the motivational effects of threat for our understanding of anxiety disorders, their investigation is still in its infancy. Pavlovian-to-Instrumental transfer is one paradigm that allows us to investigate such motivational effects of threat cues. Here, we review studies investigating aversive transfer in humans and discuss recent results on the neural circuits mediating Pavlovian-to-Instrumental transfer effects. Finally, we discuss potential limitations of the transfer paradigm and future directions for employing Pavlovian-to-Instrumental transfer for the investigation of motivational effects of fear and anxiety.

scholarly journals Predictive value of implicit and explicit self-esteem for the recurrence of depression and anxiety disorders: A 3-year follow-up study.

2020 ◽  
Vol 129 (8) ◽  
pp. 788-798
Author(s):  
Lonneke A. van Tuijl ◽  
Elise C. Bennik ◽  
Brenda W. J. H. Penninx ◽  
Philip Spinhoven ◽  
Peter J. de Jong
Keyword(s):  
Anxiety Disorders ◽  
Predictive Value ◽  
Self Esteem ◽  
Depression And Anxiety ◽  
Follow Up Study ◽  
Implicit And Explicit

scholarly journals What happens to anxiety disorders in later life?

2002 ◽  
Vol 24 (suppl 1) ◽  
pp. 74-80 ◽  
Author(s):  
Gerard JA Byrne
Keyword(s):  
Anxiety Disorders ◽  
Older People ◽  
Older Patients ◽  
Depressive Disorders ◽  
Late Onset ◽  
Reliability And Validity ◽  
Later Life ◽  
Pharmacological Interventions ◽  
Measuring Change ◽  
Pathological Anxiety

Anxiety disorders decline in prevalence with advancing age but remain more common than depressive disorders. They are often of late-onset and there is frequent comorbidity with depressive disorders and physical illness. While anxiety disorders in older people are likely to respond to the same non-pharmacological interventions that have been shown to work in younger people, there is currently little formal evidence of this. Although there is some evidence that the non-benzodiazepine anxiolytic medication, buspirone, is effective against late life anxiety symptoms, clinical trials in older people with rigorously diagnosed anxiety disorders are needed. An anxiety scale with demonstrated reliability and validity in older people is needed for screening for pathological anxiety and for measuring change in older patients undergoing treatment for anxiety disorders.

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