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

Psychopharmacology (Berl). 2013 Dec;230(3):465-76. doi: 10.1007/s00213-013-3179-5. Epub 2013 Jun 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Clonidine / pharmacology
  • Dextroamphetamine / pharmacology*
  • Hypothalamo-Hypophyseal System / metabolism
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Norepinephrine / metabolism*
  • Pituitary-Adrenal System / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reflex, Startle / drug effects
  • Reflex, Startle / physiology
  • Stress Disorders, Post-Traumatic / physiopathology*
  • Substance-Related Disorders / physiopathology*
  • Time Factors


  • Clonidine
  • Dextroamphetamine
  • Norepinephrine