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Cotinine: A Therapy for Memory Extinction in Post-traumatic Stress Disorder

A Correction to this article was published on 23 April 2018

This article has been updated

Abstract

Post-traumatic stress disorder (PTSD) is a mental disorder that may develop after exposure to exceptionally threatening or unescapable horrifying events. Actual therapies fail to alleviate the emotional suffering and cognitive impairment associated with this disorder, mostly because they are ineffective in treating the failure to extinguish trauma memories in a great percentage of those affected. In this review, current behavioral, cellular, and molecular evidence supporting the use of cotinine for treating PTSD are reviewed. The role of the positive modulation by cotinine of the nicotinic acetylcholine receptors (nAChRs) and their downstream effectors, the protection of astroglia, and the inhibition of microglia in the PTSD brain are also discussed.

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Change history

  • 23 April 2018

    The original version of this article unfortunately contained mistake in its Funding inforation. That is, the Grant Number has an error currently read as “This work was supported by the Fondo de Ciencia y Tecnología (FONDECYT) de Chile, Grant #1150149”.

Abbreviations

AD:

Alzheimer’s disease

Akt:

Protein kinase B

AMY:

Amygdala

BDNF:

Brain-derived neurotrophic factor

CaMKK:

Calmodulin-dependent protein kinase (CaM kinase)

CAPS:

Clinician-administered PTSD scale

CR:

Conditioned response

CREB:

Cyclic AMP response element-binding protein

DSM:

Diagnostic statistical manual of mental disorders

FC:

Fear conditioning

fMRI:

Functional magnetic resonance imaging or functional MRI

GABA:

Gamma-aminobutyric acid

ICN:

Intercalated nuclei

GSK3:

Glycogen synthase kinase

mTOR:

Mammalian target of rapamycin

NFκB:

Nuclear factor kappa-light-chain enhancer of activated B cells

nAChRs:

Nicotinic acetylcholine receptors

NT:

Neurotrophin

PDK-1:

PI-dependent kinase 1

PFC:

Prefrontal cortex

PTSD:

Post-traumatic stress disorder

VEGF:

Vascular and endothelial growth factor

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Acknowledgements

The work was done with the support of the research and the Bay Pines VA healthcare system, USA. This material is the result of work supported with resources and the use of facilities at the Bay Pines VA Healthcare System and the research and development divisions of the Universidad San Sebastián, Chile. The contents do not necessarily represent the views of the Department of Veterans Affairs or the United States Government.

Funding

This work was supported by the Fondo de Ciencia y Tecnología (FONDECYT) de Chile, Grant #1150149.

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Correspondence to Gjumrakch Aliev or Valentina Echeverria.

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Mendoza, C., Barreto, G.E., Iarkov, A. et al. Cotinine: A Therapy for Memory Extinction in Post-traumatic Stress Disorder. Mol Neurobiol 55, 6700–6711 (2018). https://doi.org/10.1007/s12035-018-0869-3

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Keywords

  • Post-traumatic stress disorder
  • Cotinine
  • Fear
  • Inflammation
  • Nicotinic receptor
  • Extinction