Psychopharmacology

, Volume 189, Issue 2, pp 165–173

Effect of paroxetine on enhanced contextual fear induced by single prolonged stress in rats

  • Terumichi Takahashi
  • Shigeru Morinobu
  • Yasuyuki Iwamoto
  • Shigeto Yamawaki
Original Investigation

DOI: 10.1007/s00213-006-0545-6

Cite this article as:
Takahashi, T., Morinobu, S., Iwamoto, Y. et al. Psychopharmacology (2006) 189: 165. doi:10.1007/s00213-006-0545-6

Abstract

Rationale

Single prolonged stress (SPS) is an animal model of posttraumatic stress disorder (PTSD) that can reproduce enhanced hypothalamo-pituitary-adrenal negative feedback.

Objectives

We examined whether SPS can produce an enhanced psychophysiological reactivity to laboratory stressors unrelated to trauma and whether paroxetine (PRX) can alleviate the enhanced anxiety and fear response in rats subjected to SPS. Furthermore, the effect of PRX on pain sensitivity was examined in rats with and without SPS.

Methods

Rats were subjected to SPS (restraint for 2 h, forced swim for 20 min, and ether anesthesia) and then kept undisturbed for 14 days. After that, contextual fear response was assessed. Twenty-four hours after foot shock conditioning, freezing behavior was measured during reexposure to the shock environment for 3 min. Pain sensitivity was assessed by the flinch–jump test. PRX (0.01, 0.03, or 0.1 mg/mL) was chronically administered orally in drinking water.

Results

Rats subjected to SPS showed a significant increase in contextual freezing compared to rats without SPS. Chronic administration of PRX at concentrations of 0.03 and 0.1 mg/mL (which produced serum concentrations similar to those that are clinically relevant) caused significant suppression of the enhanced contextual freezing. Acute administration of PRX at a dose producing clinically relevant serum concentrations did not affect the enhanced freezing.

Conclusions

Our results suggest that SPS can reproduce behavioral alteration similar to that observed in patients with PTSD, and this elevated fear response can be alleviated by the chronic administration of PRX at doses producing clinically relevant serum concentrations.

Keywords

PTSD Animal model Contextual fear Fear conditioning Paroxetine Rat Single prolonged stress (SPS) 

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Terumichi Takahashi
    • 1
  • Shigeru Morinobu
    • 1
  • Yasuyuki Iwamoto
    • 1
  • Shigeto Yamawaki
    • 1
  1. 1.Department of Psychiatry and Neurosciences, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical SciencesHiroshima UniversityHiroshimaJapan

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