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Traumatic stress in rats induces noradrenergic-dependent long-term behavioral sensitization: role of individual differences and similarities with dependence on drugs of abuse

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Abstract

Rationale

The aim of this paper is to provide evidence for the hypothesis that posttraumatic stress disorder (PTSD) and drug addiction rely on common processes.

Objective

Our objective is to show that a noradrenergic-dependent behavioral sensitization occurs after the development of PTSD, in a way similar to that recently demonstrated after repeated drug injections.

Methods

Rats classified into high and low responders to novelty (HR/LR) were subjected to a single prolonged stress (SPS). Cross-sensitization was evaluated after d-amphetamine injection (1.0 mg/kg) in a locomotor activity test given either 4, 15, or 90 days later. To determine the involvement of the noradrenergic system, rats were injected with the α2-receptor agonist, clonidine (20 μg/kg), during the SPS. Subsequently, their auditory startle response (ASR) and cross-sensitization were assessed.

Results

SPS affected both the hypothalamic–pituitary–adrenal axis and the ASR, replicating some PTSD-like symptoms. Behavioral sensitization was found after 15, 21, and 90 days after the SPS in LR rats, and a behavioral desensitization in HR rats after 15 days. Clonidine delivered during the SPS prevented the behavioral sensitization in LR rats, as well as the effects on ASR in HR and LR rats.

Conclusions

Exposure to SPS is shown to affect behavior and induce a behavioral sensitization to d-amphetamine that is modulated by individual differences. Both of these effects depend on the noradrenergic system. Altogether, the present results (1) replicate findings obtained after repeated drug exposure and (2) strengthen our hypothesis of a common physiological basis between PTSD and drug addiction.

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Acknowledgments

Daniel Toledano was supported by DGA/CNRS (Délégation générale de l’armement/Centre National de la recherche scientifique) PhD fellowship. We thank Pascale Veyrac and Nathalie Samson-Desvignes for the animal care, P. Ragot, A. Trad, and L. Ager for their assistance for the experimental studies and Prof DC Riccio for correcting the English text.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. CNRS, Centre de Neurosciences Paris Sud, UMR 8195, Bât 446, Université Paris Sud, 91405, Orsay Cedex, France

    Daniel Toledano & Pascale Gisquet-Verrier

  2. Université Paris-Sud, UMR 8195, 91405, Orsay, France

    Daniel Toledano & Pascale Gisquet-Verrier

  3. Laboratoire de Physiologie et de Physiopathologie des Maladies du système Nerveux Central, CNRS UMR 7224, INSERM UMRS 952, Université Pierre et Marie Curie, 75005, Paris, France

    Jean-Pol Tassin

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  1. Daniel Toledano
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Correspondence to Pascale Gisquet-Verrier.

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Toledano, D., Tassin, JP. & Gisquet-Verrier, P. Traumatic stress in rats induces noradrenergic-dependent long-term behavioral sensitization: role of individual differences and similarities with dependence on drugs of abuse. Psychopharmacology 230, 465–476 (2013). https://doi.org/10.1007/s00213-013-3179-5

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