Effect of paroxetine on enhanced contextual fear induced by single prolonged stress in rats.
BACKGROUND
Single prolonged stress (SPS) is an animal model of posttraumatic stress disorder (PTSD) that can reproduce enhanced hypothalamo-pituitary-adrenal negative feedback.


OBJECTIVE
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.
Takahashi
Terumichi
T
Department of Psychiatry and Neurosciences, Division of Frontier Medical Science, Hiroshima University, Minami-ku, Hiroshima, 734-8551, Japan.
Morinobu
Shigeru
S
Iwamoto
Yasuyuki
Y
Yamawaki
Shigeto
S
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003213:Conditioning, Psychological; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D004986:Ether / Q000494:pharmacology; D005239:Fear / Q000187:drug effects* / Q000523:psychology; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D017374:Paroxetine / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy / Q000523:psychology*; D013550:Swimming; D014828:Vocalization, Animal / Q000187:drug effects
D004986:Ether; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors