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


OBJECTIVE
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.
Matuszewich
Leslie
L
Department of Psychiatry, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106, USA. lmatusze@niu.edu
Yamamoto
Bryan K
BK
D000662:Amphetamines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004285:Dogs; D005334:Fever / Q000139:chemically induced* / Q000150:complications; D006213:Hallucinogens / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects; D013312:Stress, Physiological / Q000150:complications / Q000503:physiopathology*
D000662:Amphetamines; D006213:Hallucinogens; D044348:Receptors, Serotonin, 5-HT2; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine