Noradrenergic Regulation of Fear and Drug-Associated Memory Reconsolidation

Otis, James M.; Werner, Craig T.; Mueller, Devin

doi:10.1038/npp.2014.243

Cited by 66 publications

(49 citation statements)

References 109 publications

(185 reference statements)

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“…In addition to behavioral procedures, pharmacological manipulations have been used to target the reconsolidation of fear memories as previously described (Nader and Hardt, 2009 (Otis et al, 2015;Soeter and Kindt, 2011). Despite the early promise in healthy humans, results have been underwhelming in clinical populations studied to-date (Wood et al, 2015) (additional data is pending, see clinicaltrials.gov identifier NCT01127568).…”

Section: Future Directions and Clinical Implicationsmentioning

confidence: 99%

Stress and Fear Extinction

Maren

Holmes

2015

Neuropsychopharmacol

341

264

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Stress has a critical role in the development and expression of many psychiatric disorders, and is a defining feature of posttraumatic stress disorder (PTSD). Stress also limits the efficacy of behavioral therapies aimed at limiting pathological fear, such as exposure therapy. Here we examine emerging evidence that stress impairs recovery from trauma by impairing fear extinction, a form of learning thought to underlie the suppression of trauma-related fear memories. We describe the major structural and functional abnormalities in brain regions that are particularly vulnerable to stress, including the amygdala, prefrontal cortex, and hippocampus, which may underlie stress-induced impairments in extinction. We also discuss some of the stress-induced neurochemical and molecular alterations in these brain regions that are associated with extinction deficits, and the potential for targeting these changes to prevent or reverse impaired extinction. A better understanding of the neurobiological basis of stress effects on extinction promises to yield novel approaches to improving therapeutic outcomes for PTSD and other anxiety and trauma-related disorders.

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Section: Future Directions and Clinical Implicationsmentioning

confidence: 99%

Stress and Fear Extinction

Maren

Holmes

2015

Neuropsychopharmacol

341

264

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“…There is also extensive evidence from preclinical studies that NE transmission is dysregulated in animal models of PTSD and AUD. A detailed discussion of these findings is beyond the scope of this article; however, these topics have been comprehensively reviewed (PTSD and NE: Berridge et al 2012;Morilak et al 2005;Otis et al 2015;AUD and NE: Becker 2012;Weinshenker & Schroeder 2007). Very little work has focused on pathophysiological changes in NE transmission in animal models of comorbid PTSD and AUD.…”

Section: High Ne and Hyperarousalmentioning

confidence: 99%

Neurobiology of comorbid post‐traumatic stress disorder and alcohol‐use disorder

Gilpin

Weiner

2016

Genes Brain and Behavior

127

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Post-traumatic stress disorder (PTSD) and alcohol-use disorder (AUD) are highly comorbid in humans. Although we have some understanding of the structural and functional brain changes that define each of these disorders, and how those changes contribute to the behavioral symptoms that define them, little is known about the neurobiology of comorbid PTSD and AUD, which may be due in part to a scarcity of adequate animal models for examining this research question. The goal of this review is to summarize the current state-of-the-science on comorbid PTSD and AUD. We summarize epidemiological data documenting the prevalence of this comorbidity, review what is known about the potential neurobiological basis for the frequent co-occurrence of PTSD and AUD and discuss successes and failures of past and current treatment strategies. We also review animal models that aim to examine comorbid PTSD and AUD, highlighting where the models parallel the human condition, and we discuss the strengths and weaknesses of each model. We conclude by discussing key gaps in our knowledge and strategies for addressing them: in particular, we (1) highlight the need for better animal models of the comorbid condition and better clinical trial design, (2) emphasize the need for examination of subpopulation effects and individual differences and (3) urge cross-talk between basic and clinical researchers that is reflected in collaborative work with forward and reverse translational impact.

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“…The fear circuit underlying memory reconsolidation is unclear, and finding a window for tDCS to manipulate this circuit is challenging. It has been proposed that noradrenergic and glutamergic inputs to the basolateral nucleus of the amygdala (BLA) might restabilize glutamate-dependent plasticity during reconsolidation [15]. Furthermore, the authors propose that BLA output neurons to the central nucleus of the amygdala control aversive responses during emotional memory expression.…”

Section: Introductionmentioning

confidence: 99%

No Effect of Cathodal Transcranial Direct Current Stimulation on Fear Memory in Healthy Human Subjects

2016

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Background: Studies have demonstrated that fear memories can be modified using non-invasive methods. Recently, we demonstrated that anodal transcranial direct current stimulation (tDCS) of the right dorsolateral prefrontal cortex is capable of enhancing fear memories. Here, we examined the effects of cathodal tDCS of the right dorsolateral prefrontal cortex during fear reconsolidation in humans. Methods: Seventeen young, healthy subjects were randomly assigned to two groups, which underwent fear conditioning with mild electric stimuli paired with a visual stimulus. Twenty-four hours later, both groups were shown a reminder of the conditioned fearful stimulus. Shortly thereafter, they received either tDCS (right prefrontal—cathodal, left supraorbital—anodal) for 20 min at 1 mA, or sham stimulation. A day later, fear responses of both groups were compared. Results: On Day 3, during fear response assessment, there were no significant differences between the tDCS and sham group (p > 0.05). Conclusion: We conclude that cathodal tDCS of the right dorsolateral prefrontal cortex (right prefrontal—cathodal, left supraorbital—anodal) did not influence fear memories.

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Noradrenergic Regulation of Fear and Drug-Associated Memory Reconsolidation

Cited by 66 publications

References 109 publications

Stress and Fear Extinction

Stress and Fear Extinction

Neurobiology of comorbid post‐traumatic stress disorder and alcohol‐use disorder

No Effect of Cathodal Transcranial Direct Current Stimulation on Fear Memory in Healthy Human Subjects

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