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

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Abstract

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-HT2A/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-HT2A/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.

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Acknowledgements

This work was supported by National Institutes of Health grants DA07606 and DA05937-02 and by Department of Defense grant 17-99-1-9479.

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Author notes

  1. Bryan K. Yamamoto

    Present address: Department of Pharmacology, School of Medicine, Boston University, Boston, MA 02118, USA

Authors and Affiliations

  1. Department of Psychiatry, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106, USA

    Leslie Matuszewich & Bryan K. Yamamoto

  2. Department of Psychology, Northern Illinois University, DeKalb, IL 60115, USA

    Leslie Matuszewich

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Correspondence to Leslie Matuszewich.

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Matuszewich, L., Yamamoto, B.K. Long-lasting effects of chronic stress on DOI-induced hyperthermia in male rats. Psychopharmacology 169, 169–175 (2003). https://doi.org/10.1007/s00213-003-1498-7

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