Systemic or intra-prelimbic cortex infusion of prazosin impairs fear memory reconsolidation

Monte, Fabricio H Do; Souza, Rimenez R.; Wong, Ting; Carobrez, A.P.

doi:10.1016/j.bbr.2013.01.031

Cited by 31 publications

(23 citation statements)

References 36 publications

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“…Recent data also reveal that a 1 -AR activity is required for fear memory reconsolidation. Systemic or intraprelimbic medial prefrontal cortex administration of the a 1 -AR antagonist prazosin prevents fear memory reconsolidation, an effect that reduces cue-induced fear expression for at least 3 weeks (Do Monte et al, 2013). Interestingly, these effects conflict with data revealing that prelimbic b-AR blockade does not disrupt reconsolidation of drug-associated memories (Otis et al, 2013), indicating differences between paradigms or between mechanisms required for reconsolidation processes in the prelimbic cortex.…”

Section: Rodent Studiescontrasting

confidence: 52%

“…For example, inhibition of a 1 -and b-adrenergic receptor (AR) activity during reconsolidation leads to memory disruption within both appetitive and aversive memory paradigms (Bernardi et al, 2006(Bernardi et al, , 2009Do Monte et al, 2013;Gazarini et al, 2013;Milton et al, 2008b;Przybyslawski et al, 1999;Wouda et al, 2010). Furthermore, disruption of noradrenergic signaling during reconsolidation reduces long-term emotional memory in healthy humans (for a recent meta-analysis, see Lonergan et al, 2013), is associated with better quality of life among PTSD patients (Poundja et al, 2012), and is capable of reducing cue-induced cravings among patients with cocaine addiction (Saladin et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Noradrenergic Regulation of Fear and Drug-Associated Memory Reconsolidation

Otis

Werner

Mueller

2014

Neuropsychopharmacol

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Emotional and traumatic experiences lead to the development of particularly strong memories that can drive neuropsychiatric disorders, such as posttraumatic stress disorder (PTSD) and drug addiction. Disruption of these memories would therefore serve as a powerful treatment option, and targeting the pathologic emotional, but not declarative, component of a memory would be ideal for clinical intervention. Research reveals that after retrieval of a consolidated memory, the memory can be destabilized, and must then be reconsolidated through synaptic plasticity to allow subsequent retrieval. Disruption of reconsolidation-related plasticity would therefore impair specific, reactivated memories. Noradrenergic signaling strengthens synaptic plasticity and is essential for encoding the emotional components of memory. Consistent with this, investigations have now revealed that noradrenergic signaling is a critical mechanism for reconsolidation of emotional memories in rodent and human models. Here, we discuss these investigations and promising clinical trials indicating that disruption of noradrenergic signaling during reconsolidation may abolish the pathologic emotional, but not declarative, component of memories allowing alleviation of neuropsychiatric disorders including PTSD and drug addiction.

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Section: Rodent Studiescontrasting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Noradrenergic Regulation of Fear and Drug-Associated Memory Reconsolidation

Otis

Werner

Mueller

2014

Neuropsychopharmacol

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“…The AC cortex is also recruited to reconsolidate recent and remote contextual fear memories (Einarsson and Nader 2012). Involvement of the PL cortex in recent olfactory fear memory reconsolidation has been reported (Do Monte et al 2013). It is still unknown, however, whether the PL cortex works correspondingly with the AC cortex to reconsolidate learned fear over time.…”

mentioning

confidence: 99%

“…The medial prefrontal cortex has long been implicated in fear memory processing and its extinction in rats (Santos-Anderson and Routtenberg 1976;Morgan et al 1993;Morgan and LeDoux 1995;Joel et al 1997;Milad and Quirk 2002;Thomas et al 2002;Quinn et al 2008;Roozendaal et al 2009;Do Monte et al 2013;Gonzalez et al 2013). However, whether and how its anterior cingulate (AC), prelimbic (PL), and infralimbic (IL) subregions ( Fig.…”

mentioning

confidence: 99%

Activity in prelimbic cortex subserves fear memory reconsolidation over time

et al. 2014

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The prelimbic cortex has been implicated in the consolidation of previously learned fear. Herein, we report that temporarily inactivating this medial prefrontal cortex subregion with the GABA A agonist muscimol (4.0 nmol in 0.2 mL per hemisphere) was able to equally disrupt 1-, 7-, and 21-d-old contextual fear memories after their brief retrieval in rats. In all cases, this effect was prevented when memory reactivation was omitted. These results indicate that recent and remote fear memories are susceptible to reconsolidation blockade induced by prelimbic cortex inactivation. It was also demonstrated that the disrupting effect of prelimbic cortex inactivation on fear memory persisted over 11 d, and did not show extinction-related features, such as reinstatement. Infusing the same dose and volume of muscimol bilaterally into the infralimbic cortex after brief retrieval/reactivation of the fear memory did not disrupt it, as seen in prelimbic cortex-inactivated animals. The expression of Zif268/Egr1, the product of an immediate early gene related to memory reconsolidation, was also less pronounced in the infralimbic cortex than in prelimbic cortex following memory retrieval/reactivation. Altogether, the present findings highlight that activity in the prelimbic cortex may reestablish reactivated aversive memories and, therefore, contribute to their maintenance over time.

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“…Further evidence for predictive validity for SSRI effects in patients is that acute SSRI treatment potentiates fear expression in conditioned fear models, similar to accounts of increased anxiety symptoms in patients in the initial phase of SSRI treatment (Garcia-Leal et al 2010;Grillon et al 2007;Silva et al 2001). Effects of prazosin, used for treating nightmares in PTSD patients and which has some efficacy in animal models of conditioned fear responding, have not been studied yet in these human models (Do Monte et al 2013;Raskind et al 2013). This lack of data is partly due to the requirement for incremental dosing increases over weeks to reach therapeutic levels necessary for efficacy for treatment of nightmares in PTSD, reducing the feasibility of using this compound for validation studies.…”

Section: Is Conditioned Fear Responding Sensitive To Drugs That Are Ementioning

confidence: 99%

On the Road to Translation for PTSD Treatment: Theoretical and Practical Considerations of the Use of Human Models of Conditioned Fear for Drug Development

Risbrough

Glenn²,

Baker

2015

Current Topics in Behavioral Neurosciences

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The use of quantitative, laboratory-based measures of threat in humans for proof-of-concept studies and target development for novel drug discovery has grown tremendously in the last 2 decades. In particular, in the field of posttraumatic stress disorder (PTSD), human models of fear conditioning have been critical in shaping our theoretical understanding of fear processes and importantly, validating findings from animal models of the neural substrates and signaling pathways required for these complex processes. Here, we will review the use of laboratorybased measures of fear processes in humans including cued and contextual conditioning, generalization, extinction, reconsolidation, and reinstatement to develop novel drug treatments for PTSD. We will primarily focus on recent advances in using behavioral and physiological measures of fear, discussing their sensitivity as biobehavioral markers of PTSD symptoms, their response to known and novel PTSD treatments, and in the case of d-cycloserine, how well these findings have translated to outcomes in clinical trials. We will highlight some gaps in the literature and needs for future research, discuss benefits and limitations of these outcome measures in designing proof-of-concept trials, and offer practical guidelines on design and interpretation when using these fear models for drug discovery.

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Systemic or intra-prelimbic cortex infusion of prazosin impairs fear memory reconsolidation

Cited by 31 publications

References 36 publications

Noradrenergic Regulation of Fear and Drug-Associated Memory Reconsolidation

Noradrenergic Regulation of Fear and Drug-Associated Memory Reconsolidation

Activity in prelimbic cortex subserves fear memory reconsolidation over time

On the Road to Translation for PTSD Treatment: Theoretical and Practical Considerations of the Use of Human Models of Conditioned Fear for Drug Development

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