Chronic treatment with fluoxetine prevents the return of extinguished auditory-cued conditioned fear

Deschaux, Olivier; Spennato, Guillaume; Moreau, Jean‐Luc; García, René

doi:10.1007/s00213-010-2134-y

Cited by 48 publications

(36 citation statements)

References 31 publications

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“…However, chronic fluoxetine may also prevent return of extinguished fear and facilitate extinction in female rats (30–32). Ultimately, an effect of chronic SSRI administration on extinction, as well as SSRI efficacy for treatment of depression and PTSD, may be driven by a change in glutamatergic transmission, as supported by recent DCS and ketamine findings.…”

Section: Pharmacotherapy Approaches To Fear- and Anxiety-related Disomentioning

confidence: 99%

An Overview of Translationally Informed Treatments for Posttraumatic Stress Disorder: Animal Models of Pavlovian Fear Conditioning to Human Clinical Trials

Bowers

Ressler

2015

Biological Psychiatry

126

101

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Posttraumatic stress disorder (PTSD) manifests after exposure to a traumatic event and is characterized by avoidance/numbing, intrusive symptoms and flashbacks, mood and cognitive disruptions, and hyperarousal/reactivity symptoms. These symptoms reflect dysregulation of the fear system likely caused by poor fear inhibition/extinction, increased generalization, and/or enhanced consolidation or acquisition of fear. These phenotypes can be modeled in animal subjects using Pavlovian fear conditioning, allowing investigation of the underlying neurobiology of normative and pathological fear. Pre-clinical studies reveal a number of neurotransmitter systems and circuits critical for aversive learning and memory, which have informed the development of therapies used in human clinical trials. In this review, we discuss the evidence for a number of established and emerging pharmacotherapies and device-based treatments for PTSD that have been developed via a bench to bedside translational model.

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Section: Pharmacotherapy Approaches To Fear- and Anxiety-related Disomentioning

confidence: 99%

An Overview of Translationally Informed Treatments for Posttraumatic Stress Disorder: Animal Models of Pavlovian Fear Conditioning to Human Clinical Trials

Bowers

Ressler

2015

Biological Psychiatry

126

101

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“…Administration of SSRIs is a common pharmacological approach to the treatment of mood and anxiety disorders including panic disorder. Recent studies indicate that chronic administration of the SSRI fluoxetine improves extinction retention (22)(23)(24), suggesting a potential mechanism underlying its anxiolytic and antidepressant effects (25). Here, we test whether fluoxetine alters the 5-HTT DPF, which would further implicate the 5-HTT DPF as a mediator of both altered extinction retention and the therapeutic effects of SSRIs.…”

Section: Genetic Variation In 5-htt Polyadenylation Selectively Modulmentioning

confidence: 99%

“…To further relate the 5-HTT distal polyadenylation fraction to anxiety-related emotional processing, we treated mice with the selective serotonin reuptake inhibitor (SSRI) fluoxetine, a treatment that facilitates extinction retention (22)(23)(24), alleviates anxiety and depressive symptoms (25), and is the most commonly used pharmacological treatment for panic disorder. Chronic fluoxetine increased the 5-HTT DPF in mouse brain, suggesting that biological factors that increase the 5-HTT DPF are anxiolytic and those that decrease it are anxiogenic.…”

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confidence: 99%

Serotonin transporter polyadenylation polymorphism modulates the retention of fear extinction memory

Hartley¹,

McKenna²,

Salman³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Growing evidence suggests serotonin's role in anxiety and depression is mediated by its effects on learned fear associations. Pharmacological and genetic manipulations of serotonin signaling in mice alter the retention of fear extinction learning, which is inversely associated with anxious temperament in mice and humans. Here, we test whether genetic variation in serotonin signaling in the form of a common human serotonin transporter polyadenylation polymorphism (STPP/rs3813034) is associated with spontaneous fear recovery after extinction. We show that the risk allele of this polymorphism is associated with impaired retention of fear extinction memory and heightened anxiety and depressive symptoms. These STPP associations in humans mirror the phenotypic effects of serotonin transporter knockout in mice, highlighting the STPP as a potential genetic locus underlying interindividual differences in serotonin transporter function in humans. Furthermore, we show that the serotonin transporter polyadenylation profile associated with the STPP risk allele is altered through the chronic administration of fluoxetine, a treatment that also facilitates retention of extinction learning. The propensity to form persistent fear associations due to poor extinction recall may be an intermediate phenotype mediating the effects of genetic variation in serotonergic function on anxiety and depression. The consistency and specificity of these data across species provide robust support for this hypothesis and suggest that the little-studied STPP may be an important risk factor for mood and anxiety disorders in humans.

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“…The effect of antidepressants as enhancers of fear extinction, however, is still matter of debate. Some animal studies found facilitated extinction or extinction retention with chronic use of antidepressants [93][94][95] albeit it has not been always replicated 96 perhaps due to sex-related differences 97 . One small human study found that chronic use of antidepressants may enhance extinction although it is not clear that the BDNF pathway is the one responsible for such effects 98 .…”

Section: Discussionmentioning

confidence: 99%

Brain derived neurotrophic factor mediated learning, fear acquisition and extinction as targets for developing novel treatments for anxiety

Oliveira

Hounie

Cappi

et al. 2016

J. bras. psiquiatr.

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KeywordsBrain-derived neurotrophic factor, fear, anxiety disorders, learning, psychological extinction. Palavras-chaveFator neurotrófico derivado do cérebro, medo, transtornos de ansiedade, aprendizagem, extinção psicológica.Brain derived neurotrophic factor mediated learning, fear acquisition and extinction as targets for developing novel treatments for anxiety Aprendizado, aquisição ABSTRACTAnxiety and obsessive-compulsive related disorders are highly prevalent and disabling disorders for which there are still treatment gaps to be explored. Fear is a core symptom of these disorders and its learning is highly dependent on the activity of the neurotrophin brain--derived neurotrophic factor (BDNF). Should BDNF-mediated fear learning be considered a target for the development of novel treatments for anxiety and obsessive-compulsive related disorders? We review the evidence that suggests that BDNF expression is necessary for the acquisition of conditioned fear, as well as for the recall of its extinction. We describe the findings related to fear learning and genetic/epigenetic manipulation of Bdnf expression in animals and BDNF allelic variants in humans. Later, we discuss how manipulation of BDNF levels represents a promising potential treatment target that may increase the benefits of therapies that extinguish previously conditioned fear. RESUMOOs transtornos da ansiedade e o transtorno obsessivo-compulsivo (TOC) e transtornos relacionados são altamente prevalentes e incapacitantes. Apesar disso, ainda existem lacunas a serem exploradas em relação ao tratamento desses transtornos. O medo é um sintoma central desses transtornos e sua aprendizagem é altamente dependente da atividade do fator neurotrófico derivado do cérebro (BDNF). Porém, será que a aprendizagem de medo mediada pelo BDNF deve ser considerada um alvo para o desenvolvimento de novos tratamentos para transtornos da ansiedade, TOC e transtornos relacionados? Revisamos as evidências que sugerem que a expressão de BDNF é necessária para a aquisição do medo condicionado, bem como para a evocação de sua extinção. Descrevemos os resultados relacionados a aprendizagem de medo, manipulação genética e epigenética da expressão de Bdnf em animais e variantes alélicas de BDNF em seres humanos. Posteriormente, discutimos como a manipulação dos níveis de BDNF representa um alvo em potencial para o tratamento, o que pode aumentar os benefícios das terapias que extinguem o medo previamente condicionado. Oliveira KS et al.

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Chronic treatment with fluoxetine prevents the return of extinguished auditory-cued conditioned fear

Abstract: These data extend our previous findings and suggest that chronic fluoxetine treatment favor extinction memory by dampening the reactivation of the original tone-shock association.

Cited by 48 publications

References 31 publications

An Overview of Translationally Informed Treatments for Posttraumatic Stress Disorder: Animal Models of Pavlovian Fear Conditioning to Human Clinical Trials

An Overview of Translationally Informed Treatments for Posttraumatic Stress Disorder: Animal Models of Pavlovian Fear Conditioning to Human Clinical Trials

Serotonin transporter polyadenylation polymorphism modulates the retention of fear extinction memory

Brain derived neurotrophic factor mediated learning, fear acquisition and extinction as targets for developing novel treatments for anxiety

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