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Behavioral and Noradrenergic Sensitizations in Vulnerable Traumatized Rats Suggest Common Bases with Substance Use Disorders

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Abstract

The aim of the present study was to strengthen our hypothesis of a common physiological basis for post-traumatic stress disorder (PTSD) and substance use disorders. This paper investigates the possibility that rats exposed to a PTSD model exhibit noradrenergic and behavioral sensitization, as observed following repeated drugs of abuse injections. First, rats received a single prolonged stress (SPS), combining three consecutive stressors. They were then tested, 2 weeks after the trauma for PTSD-like symptoms to discriminate between vulnerable and resilient rats. When microdialysis was performed in the prelimbic cortex (Experiment 1), larger increases of noradrenaline (NA) release in response to amphetamine were observed in vulnerable rats when compared to control and resilient animals. Experiment 2 showed that trauma-vulnerable rats exhibited increases in locomotor activity relative to controls, in response to an exposure to trauma-associated cues. These data demonstrate that a single trauma exposure induces in vulnerable animals both, a noradrenergic sensitization evidenced within the prelimbic cortex and behavioral sensitization obtained after a physiologic activation of the noradrenergic system. However, Experiment 3 showed that when NA system was activated by amphetamine (1 mg/kg), a decrease in behavioral sensitization was obtained in vulnerable rats. We proposed that this decreased locomotor activity results from an additional stress-induced increased reactivity of mesocortical dopaminergic neurons, known to counteract the consequences of cortical noradrenergic release in rats. These results support our hypothesis that noradrenergic sensitization represents a common physiological basis, involved both in PTSD and drug addiction and suggest new common therapeutic approaches for these pathologies.

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Acknowledgments

We are very grateful to Professor D. C. Riccio for the correction of the English text. We thank Aurelie Bonilla, Céline Dubois, and Fabien Lhéricel for the animal care.

Funding

This work was supported by “les Gueules Cassées” foundation (grant number 45-2017). Claire Le Dorze was supported by a DGA-MRIS (Direction Générale de l’Armement) scholarship.

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Authors and Affiliations

  1. Institut des Neurosciences Paris-Saclay (Neuro-PSI), Université Paris-Sud, CNRS UMR 9197, Université Paris-Saclay, Bât 446, 91405, Orsay, France

    Claire Le Dorze & Pascale Gisquet-Verrier

  2. Sorbonne Universite, Neuroscience Paris Seine, UMCR18, CNRS UMR 8246, Inserm U1130, 7 Quai St Bernard, 75252, Paris, France

    Jean-Pol Tassin

  3. Institut de Recherche Biomédicale des Armées (IRBA), Brétigny sur Orge Cedex, France

    Fréderic Chauveau

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  1. Claire Le Dorze
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  2. Jean-Pol Tassin
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  3. Fréderic Chauveau
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  4. Pascale Gisquet-Verrier
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Correspondence to Pascale Gisquet-Verrier.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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The authors declare that they have no conflict of interest.

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Le Dorze, C., Tassin, JP., Chauveau, F. et al. Behavioral and Noradrenergic Sensitizations in Vulnerable Traumatized Rats Suggest Common Bases with Substance Use Disorders. Mol Neurobiol 56, 611–620 (2019). https://doi.org/10.1007/s12035-018-1053-5

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