Long-lasting effects of chronic stress on doi-induced hyperthermia in male rats

Leslie Matuszewich, Bryan K. Yamamoto

Research output: Contribution to journalArticle

36 Scopus citations


Rationale: Exposure to chronic stress can affect the serotoninergic (5-HT) system and behavioral measures associated with 5-HT. Repeated stress increases 5-HT receptor subtype 2 (5-HT2) mediated behaviors in rodents, such as wet dog shakes and head twitch. Objectives: The current study investigated whether exposure to chronic unpredictable stress would augment 5-HT 2A/C receptor-mediated hyperthermia. Furthermore, the persistence of these hyperthermic effects was investigated by testing rats up to 60 days after the stress procedure terminated. Methods: For 2 or 10 days, rats were either not stressed (controls) or exposed to chronic unpredictable stress, i.e. two stressors per day of the following: cage rotation, cold exposure, swim, restraint, light cycle manipulations, single housing, and food and water deprivation. After the termination of stress (day 3 or 11), the 5-HT 2A/C receptor agonist DOI (1.5 mg/kg) or saline, was injected and the rectal temperature of the rats was monitored. In a separate experiment, the 5-HT2 receptor antagonist, LY-53,587, was injected 30 min prior to the injection of DOI or saline. Finally, DOI was injected into rats 8, 30 or 60 days after the 10-day stress procedure ended. Results: Rats exposed to 10 days, but not 2 days, of unpredictable stress exhibited higher rectal temperatures following DOI than non-stressed rats. The DOI-induced hyperthermia was attenuated by LY-53,587. The augmentation of DOI-induced hyperthermia in stressed rats persisted when examined 8, 30 and 60 days following the stress procedure. Conclusions: The enhancement of 5-HT receptor function by chronic stress persists even after the environmental stressor is removed. This lasting increase in 5-HT receptor function may have implications for clinical disorders associated with stress, such as depression or post-traumatic stress disorder.

Original languageEnglish (US)
Pages (from-to)169-175
Number of pages7
Issue number2
StatePublished - Sep 1 2003
Externally publishedYes


  • 5-HT2 receptor
  • Chronic stress
  • Hyperthermia
  • Serotonin

ASJC Scopus subject areas

  • Pharmacology

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