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Associating Aversive Task Exposure with Pharmacological Intervention to Model Traumatic Memories in Laboratory Rodents

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Translational Methods for PTSD Research

Part of the book series: Neuromethods ((NM,volume 198))

Abstract

Post-traumatic stress disorder is associated with highly threatening and stressful events. The underlying memory is overconsolidated, leading to generalized fear expression and overall resistance to extinction- and reconsolidation-based interventions. Fear conditioning and avoidance protocols commonly used in laboratory settings induce specific and moderate-intensity aversive memories, but traumatic ones differ in quantitative and qualitative aspects. It would be appropriate to reproduce their abnormal features for studying PTSD neurobiology and assessing potential new therapeutics. After discussing the mnemonic basis of PTSD, its memory-related symptoms, and neurochemical findings underlying the traumatic memory, we aimed to review and discuss studies addressing the abovementioned question in rats and mice. Because of its potential translational value, the focus was on procedures associating an aversive task with single or combined post-training pharmacological interventions. Nearly 200 studies published since 1975 report that this protocol enhances aversive memory strength. The parallel assessment of abnormal features related to traumatic memories, such as altered specificity and susceptibility to extinction and drug-induced reconsolidation blockade, started more recently. Systemically administered drugs potentiating noradrenergic or glucocorticoid mechanisms have predominated, probably because of PTSD’s physiopathology. Other options and discrete brain infusions have provided complementary information. Currently available data indicate that aversive task exposure followed by adequate drug interference during consolidation generates more intense and generalized memories, which are less prone to modulation by behavioral and pharmacological strategies. These findings based on the bedside-to-bench approach are instructive for future analyses to advance our understanding of the underlying neurobiological mechanisms and develop more effective treatments for PTSD.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

AFC:

Auditory fear conditioning

BLA:

Basolateral amygdala

BNST:

Bed nucleus of the stria terminalis

CB1:

Cannabinoid type-1 receptor

CeA:

Central amygdala

CFC:

Contextual fear conditioning

CS:

Conditioned stimulus

dACC:

Dorsal anterior cingulate cortex

DH:

Dorsal hippocampus

DSM-5:

Diagnostic and Statistical Manual of Mental Disorders, 5th edition

eCB:

Endocannabinoid

HPA:

Hypothalamic–pituitary–adrenal axis

i.c.v.:

Intracerebroventricular

IL:

Infralimbic cortex

i.p.:

Intraperitoneal

LTP:

Long-term potentiation

mTORC1:

Mammalian target of rapamycin complex 1

ND:

Not described or retrieved

NMDA:

N-Methyl-D-aspartate

NR:

Nucleus reuniens of the thalamus

PFC:

Prefrontal cortex

PI3K:

Phosphoinositide 3-kinase

PL:

Prelimbic cortex

p.o.:

via oral, oral route

PTSD:

Post-traumatic stress disorder

SAM:

Sympathoadrenomedullary axis

s.c.:

Subcutaneous

US:

Unconditioned stimulus

VH:

Ventral hippocampus

vmPFC:

Ventromedial prefrontal cortex

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Authors and Affiliations

  1. Universidade Federal de Mato Grosso do Sul, Três Lagoas, MS, Brazil

    Lucas Gazarini

  2. Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brazil

    Cristina A. J. Stern

  3. Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil

    Leandro J. Bertoglio

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  1. Lucas Gazarini
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  2. Cristina A. J. Stern
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  3. Leandro J. Bertoglio
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Correspondence to Lucas Gazarini or Cristina A. J. Stern .

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  1. Psychiatric Institute, University of Chicago, Chicago, IL, USA

    Graziano Pinna

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Gazarini, L., Stern, C.A.J., Bertoglio, L.J. (2023). Associating Aversive Task Exposure with Pharmacological Intervention to Model Traumatic Memories in Laboratory Rodents. In: Pinna, G. (eds) Translational Methods for PTSD Research. Neuromethods, vol 198. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3218-5_13

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