Rationale: Pharmacological targeting of memory reconsolidation is a promising therapeutic strategy for the treatment of fear memory-related disorders. However, the success of reconsolidation-based approaches depends upon the effective destabilisation of the fear memory by memory reactivation.
Objectives: Here, we aimed to determine the functional involvement of dopamine D1 receptors in cued fear memory destabilisation, using systemic drug administration.
Results: We observed that direct D1 receptor agonism was not sufficient to stimulate tone fear memory destabilisation to facilitate reconsolidation disruption by the glucocorticoid receptor antagonist mifepristone. Instead, administration of the nootropic nefiracetam did facilitate mifepristone-induced amnesia, in a manner that was dependent upon dopamine D1 receptor activation. Finally, while the combined treatment with nefiracetam and mifepristone did not confer fear-reducing effects under conditions of extinction learning, there was some evidence that mifepristone reduces fear expression irrespective of memory reactivation parameters.
Conclusions: The use of combination pharmacological treatment to stimulate memory destabilisation and impair reconsolidation has potential therapeutic benefits, without risking a maladaptive increase of fear.
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http://dx.doi.org/10.1007/s00213-019-05338-5 | DOI Listing |
J Neurosci
December 2024
Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA
Excitatory synapses and the actin-rich dendritic spines on which they reside are indispensable for information processing and storage in the brain. In the adult hippocampus, excitatory synapses must balance plasticity and stability to support learning and memory. However, the mechanisms governing this balance remain poorly understood.
View Article and Find Full Text PDFNeuropharmacology
December 2024
Institute of Physiology and Pathophysiology, Heidelberg University, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany.
Neuropeptide Y (NPY) is the most abundant neuropeptide in the brain. It exerts anxiolytic and anticonvulsive actions, reduces stress and suppresses fear memory. While its effects at the behavioral and cellular levels have been well studied, much less is known about the modulation of physiological activity patterns at the network level.
View Article and Find Full Text PDFProg Neuropsychopharmacol Biol Psychiatry
December 2024
Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran; Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. Electronic address:
Post-traumatic stress disorder (PTSD) is a challenging mental health condition that affects millions of people worldwide after they experience traumatic events. The current medications often do not fully address the wide range of PTSD symptoms or the underlying brain mechanisms, prompting the need to explore new treatments. Polyphenols, which are natural compounds found in many plant-based foods, have gained interest due to their brain-protective, anti-inflammatory, and antioxidant benefits.
View Article and Find Full Text PDFBrain Behav Immun Health
February 2025
Department of Neuroscience, The Ohio State University Wexner Medical Center, USA.
Chronic stress increases the incidence of psychiatric disorders including anxiety, depression, and posttraumatic stress disorder. Repeated Social Defeat (RSD) in mice recapitulates several key physiological, immune, and behavioral changes evident after chronic stress in humans. For instance, neurons in the prefrontal cortex, amygdala, and hippocampus are involved in the interpretation of and response to fear and threatful stimuli after RSD.
View Article and Find Full Text PDFFront Behav Neurosci
December 2024
Department of Neuroscience, Developmental, and Regenerative Biology, University of Texas at San Antonio, San Antonio, TX, United States.
Safety learning during threat and adversity is critical for behavioral adaptation, resiliency, and survival. Using a novel mouse paradigm involving thermal threat, we recently demonstrated that safety learning is highly susceptible to social isolation stress. Yet, our previous study primarily considered male mice and did not thoroughly scrutinize the relative impacts of stress on potentially distinct defensive mechanisms implemented by males and females during the thermal safety task.
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