Parsons RG, Ressler KJ. Implications of memory modulation for post-traumatic stress and fear disorders. Nat Neurosci 16: 146-153

Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
Nature Neuroscience (Impact Factor: 16.1). 01/2013; 16(2):146-53. DOI: 10.1038/nn.3296
Source: PubMed


Post-traumatic stress disorder, panic disorder and phobia manifest in ways that are consistent with an uncontrollable state of fear. Their development involves heredity, previous sensitizing experiences, association of aversive events with previous neutral stimuli, and inability to inhibit or extinguish fear after it is chronic and disabling. We highlight recent progress in fear learning and memory, differential susceptibility to disorders of fear, and how these findings are being applied to the understanding, treatment and possible prevention of fear disorders. Promising advances are being translated from basic science to the clinic, including approaches to distinguish risk versus resilience before trauma exposure, methods to interfere with fear development during memory consolidation after a trauma, and techniques to inhibit fear reconsolidation and to enhance extinction of chronic fear. It is hoped that this new knowledge will translate to more successful, neuroscientifically informed and rationally designed approaches to disorders of fear regulation.

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    • "Considering the augmented Cannabis use by post-traumatic stress disorder (PTSD) patients (Kessler et al., 1995; Cornelius et al., 2010), which may present changes in endocannabinoid system functioning (Hauer et al., 2013; Neumeister et al., 2013), this conduct could represent an empirical selfmedication attempt to affect the maintenance of a dysfunctional aversive learning, which is believed to underlie this psychiatric condition (Parsons and Ressler, 2013; Trezza and Campolongo, 2013). Recent preclinical findings from our research group have supported this hypothesis, as CBD was able to mitigate aberrant and enduring fear memories by disrupting their reconsolidation process (Stern et al., 2012; Gazarini et al., in 2015). "
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    ABSTRACT: Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the major constituents of the Cannabis sativa plant, which is frequently consumed by subjects exposed to life-threatening situations to relief their symptomatology. It is still unknown, however, whether THC could also affect the maintenance of an aversive memory formed at that time when taken separately and/or in conjunction with CBD. The present study sought to investigate this matter at a preclinical level. We report that THC (0.3-10mg/kg, i.p.) was able to disrupt the reconsolidation of a contextual fear memory, resulting in reduced conditioned freezing expression for over 22 days. This effect was dependent on activation of cannabinoid type-1 receptors located in prelimbic subregion of the medial prefrontal cortex and on memory retrieval/reactivation. Since CBD may counteract the negative psychotropic effects induced by THC and has been shown to be a reconsolidation blocker, we then investigated and demonstrated that associating sub-effective doses of these two compounds was equally effective in attenuating fear memory maintenance in an additive fashion and in a dose ratio of 10 to 1, which contrasts with that commonly found in C. sativa recreational samples. Of note, neither THC alone nor CBD plus THC interfered with anxiety-related behaviors and locomotor activity, as assessed in the elevated plus-maze test, at a time point coinciding with that used to evaluate their effects on memory reconsolidation. Altogether, present findings suggest a potential therapeutic value of using THC and/or CBD to mitigate a dysfunctional aversive memory through reconsolidation disruption in post-traumatic stress disorder patients. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.
    European Neuropsychopharmacology 06/2015; 25(6):958–965. DOI:10.1016/j.euroneuro.2015.02.001 · 4.37 Impact Factor
    • ", 2012 ; de Kleine et al . , 2013 ; Parsons and Ressler , 2013 ; Difede et al . , 2014 ) . "
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    ABSTRACT: MLC901 (NurAiDII) is used as a treatment for stroke patients. It has been shown that MLC901 improves motor and cognitive recovery in ischemic and traumatic brain-injured rodents. The present study seeks to delineate cognitive effects induced by MLC901 in normal, noninjured mice. To this end, the behaviors of vehicle- and MLC901-treated C57BL/6 mice in hippocampus-dependent (passive avoidance, Morris water maze) and hippocampus-independent (novel object recognition) cognitive tasks are compared. The potential influence of the compound on the anxiety level and nycthemeral rhythm of mice is also assessed. In addition, the long-term effects of MLC901 on hippocampal neurogenesis are measured. The results clearly demonstrate that MLC901 promotes extinction in passive avoidance and reversal learning in the Morris water maze and improves the performance of mice in novel object recognition. In parallel, this study shows the long-term proneurogenesis effects of MLC901 that result in the increase in the number of mature neurons in the hippocampus. If these observations can be extended to humans, then MLC901 could represent a promising therapeutic strategy. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Journal of Neuroscience Research 03/2015; 93(11). DOI:10.1002/jnr.23591 · 2.59 Impact Factor
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    • "contextual fear; Abrari et al., 2008; Dę biec and Ledoux, 2004) and in some cases in humans suffering from PTSD (Pitman et al., 2002; Pitman and Delahanty, 2005; Brunet et al., 2008, 2011; Soeter and Kindt, 2011; Kindt and Soeter, 2013). However, more recent, larger studies have not found a significant effect of propranolol administration after trauma (Sharp et al., 2010; Parsons and Ressler, 2013). Thus, new strategies are needed in the hope of alleviating such 'memory disorders'. "
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    ABSTRACT: Stress alters the formation of long-term memory (LTM) in Lymnaea. When snails are exposed to more than one stressor, however, how the memory is altered becomes complicated. Here we investigated how multiple stressors applied in a specific pattern affect an aspect of memory not often studied in regards to stress - reconsolidation. We hypothesized that the application of a sequence of stressors would block the reconsolidation process. Reconsolidation occurs following activation of a previously formed memory. Sequential crowding and handling were used as the stressors to block reconsolidation. When the two stressors were sequentially presented immediately following memory activation reconsolidation was blocked. However, if the sequential presentation of the stressors was delayed for 1h after memory activation reconsolidation was not blocked. That is, LTM was observed. Finally, presentation of either stressor alone did not block reconsolidation. Thus stressors can block reconsolidation, which may be preferable to pharmacological manipulations.
    Journal of Experimental Biology 01/2015; 218(6). DOI:10.1242/jeb.114876 · 2.90 Impact Factor
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