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Noradrenaline and Post-traumatic Stress Disorder

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Comprehensive Guide to Post-Traumatic Stress Disorder

Abstract

Noradrenaline (NA), a well known catecholamine has become the key transmitter involved in the generation of the autonomic symptoms present in the post-traumatic stress disorder (PTSD). It is present in the specialized noradrenergic pathways and in the cell nuclei located in the central nervous system that are involved in the pathophysiology of the disease. The locus coeruleus (LC) in the rostral pons is a region that has high NA content and it forms the center of the neurochemical traffic of PTSD. Experiments in rats have shown that NA content is increased in the LC in “cat litter” tests. NA levels in the cerebrospinal fluid increase in response to psychological stressors. The hippocampus receives NA only from the LC and the LC also sends efferents to the neocortex and the amygdala. The β adrenergic receptors located in the lateral amygdala have been shown to be involved in fear conditioning. Projections arising from the LC also innervate the paraventricular nucleus of the hypothalamus, an important structure acting as a sympathetic premotor nucleus, a central controller of autonomic functions. The LC also receives reciprocal projections from these regions. Human data have also revealed that people with high catecholamine levels are more prone to develop PTSD. It may be accepted that excessive adrenergic activation following a traumatic event may enhance the memory consolidation of the event and increase the frequency of re-experiencing the event upon confronting a reminder. The activity of NA present in synapses is terminated by NA transporters (NET). Polymorphisms in enzymes like catechol-O-methyl transferase which is responsible for the cleavage of NA and in the human NET may also play important roles in the development and maintenance of the disease. Various agents affecting noradrenergic receptors may further become therapeutic tools. Yohimbine, an α2 adrenergic receptor antagonist can induce flashbacks and as the distribution of adrenergic α2c receptor is restricted to the CNS, this subtype has been the subject of many investigations of psychiatric diseases including PTSD. As α2 receptors are presynaptic receptors and control the release of NA, inhibition of these presynaptic receptors may also cause an increase in NA synaptic levels. Clinical trials to date have shown promising results for prazosin, an α1 adrenergic receptor blocker. Unfortunately, the trials performed with guanfacine, an α2 adrenergic receptor agonist, were not effective in PTSD. Propranolol, a nonselective β adrenergic receptor antagonist may help to prevent the disease if administered early following the trauma.

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Abbreviations

A:

Adrenaline

BLA:

Basolateral nucleus of the amygdala

CAPS:

Clinical-administered PTSD scale

CeA:

Central nucleus of amygdala

CNS:

Central nervous system

COMT:

Catechol-O-methyltransferase

CRF:

Corticotropin-releasing factor

DA:

Dopamine

DOPAC:

3,4-dihydroxyphenylacetic acid

ENT:

Extraneuronal transporter or uptake 2

GABA:

Gamma-aminobutyric acid

HNET:

Human norepinephrine transporter

LC:

Locus coeruleus

NA:

Noradrenaline

NET:

Norepinephrine transporter, previously called uptake 1

OCT1, OCT2, OCT3:

Organic cation transporters 1, 2, 3

PTSD:

Posttraumatic stress disorder

PVN:

Paraventricular nucleus of the hypothalamus

VMAT2:

Vesicular monoamine transporter

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Authors and Affiliations

  1. Department of Medical Pharmacology, School of Medicine, Marmara University, Başıbüyük Health Campus, Basic Medical Sciences Building No:9/1 Başıbüyük, 34854, Maltepe, Istanbul, Turkey

    M. Zafer Gören

  2. Department of Biophysics, School of Medicine, Marmara University, Başıbüyük Health Campus, Basic Medical Sciences Building No:9/1 Başıbüyük, 34854, Maltepe, Istanbul, Turkey

    Hülya Cabadak

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  1. M. Zafer Gören
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  2. Hülya Cabadak
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Correspondence to M. Zafer Gören .

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Editors and Affiliations

  1. Buckinghamshire New University, Uxbridge, Middlesex, United Kingdom

    Colin R. Martin

  2. Kings College, London, United Kingdom

    Victor R. Preedy

  3. University of Westminster, London, United Kingdom

    Vinood B. Patel

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Gören, M.Z., Cabadak, H. (2015). Noradrenaline and Post-traumatic Stress Disorder. In: Martin, C., Preedy, V., Patel, V. (eds) Comprehensive Guide to Post-Traumatic Stress Disorder. Springer, Cham. https://doi.org/10.1007/978-3-319-08613-2_26-1

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  • DOI: https://doi.org/10.1007/978-3-319-08613-2_26-1

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