Involvement of the ventral tegmental area in a rodent model of post-traumatic stress disorder

Nadia S Corral-Frias, Ryan P Lahood, Kimberly E Edelman-Vogelsang, Edward D French, Jean-Marc Fellous

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Post-traumatic stress disorder (PTSD) is an anxiety disorder of considerable prevalence in individuals who have experienced a traumatic event. Studies of the neural substrate of this disorder have focused on the role of areas such as the hippocampus, the amygdala and the medial prefrontal cortex. We show that the ventral tegmental area (VTA), which directly modulates these areas, is part of this circuitry. Using a rat model of PTSD, we show that a brief but intense foot shock followed by three brief reminders can cause long-term behavioral changes as shown by anxiety-like, nociception, and touch-sensitivity tests. We show that an intraperitoneal injection of a dopamine (DA) antagonist or a bilateral inactivation of the VTA administered immediately before the traumatic event decrease the occurrence or intensity of these behavioral changes. Furthermore, we show that there is a significant decrease of baseline VTA dopaminergic but not GABAergic cell firing rates 2 weeks after trauma. Our data suggest that VTA DA neurons undergo long-term physiological changes after trauma and that this brain area is a crucial part of the circuits involved in PTSD symptomatology.

Original languageEnglish
Pages (from-to)350-63
Number of pages14
JournalNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Volume38
Issue number2
DOIs
StatePublished - Jan 2013
Externally publishedYes

Bibliographical note

Funding Information:
We would like to thank Stephen Brookshire, Julia Cremer, and Chu Qin for their technical assistance, Tally Largent-Milnes and Beatriz Fiorivanti for their helpful comments and training, Dr Todd Vanderah for the use of space and technical assistance, and Dr Jose Valdés for all the helpful comments. This work was supported in part by CONACyT (NSCF) and NSF grant CRCNS 1010172 (J-MF).

Keywords

  • Action Potentials/physiology
  • Animals
  • Anxiety/physiopathology
  • Avoidance Learning/physiology
  • Disease Models, Animal
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Stress Disorders, Post-Traumatic/physiopathology
  • Ventral Tegmental Area/physiopathology

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