TY - JOUR
T1 - Influence of the estrous cycle on tolerance development to LPS-induced sickness behaviors in rats
AU - Engeland, Christopher G.
AU - Kavaliers, Martin
AU - Ossenkopp, Klaus Peter
N1 - Funding Information:
This research was supported by operating and equipment grants from the Natural Sciences and Engineering Research Council of Canada to MK and K-PO. It was also made possible by equipment and software support from AccuScan Inc (Columbus OH). CGE was supported by an Ontario Graduate Scholarship. The authors thank Drs Elizabeth Hampson and Anne Konkle for valuable input concerning the hormonal assays, Dr Tom Kennedy for helpful insight concerning the estrous cycle, Ms Kay Noh for performing the RIAs, and Drs David Sherry and John Wiebe for the use of some laboratory equipment.
PY - 2006/5
Y1 - 2006/5
N2 - The relations between the estrous cycle, inflammatory responses and the development of tolerance to endotoxin were examined. Female Long-Evans rats were injected intraperitoneally with lipopolysaccharide (LPS; 200 μg/kg) or saline vehicle at 08:00 h on either diestrus (D) or proestrus (P). Ninety-five minutes after injection locomotor activity was assessed in an automated non-novel open-field for 20 min. To assess tolerance development to LPS, rats were re-injected at the next identical stage (i.e. 4 days later; groups: DD, PP) or at the alternate stage (i.e. 6 days later; groups: DP, PD) of the estrous cycle and locomotor activity was again assessed. On Test Day 1 all groups injected with LPS exhibited similar significant activity decrements, regardless of the stage of the estrous cycle. However, on Test Day 2 rats which received both injections of LPS during proestrus (PP) showed no signs of tolerance development, whereas rats in all other groups were tolerant to LPS. In a follow up study, the time between injections was extended to 8 days. Still the animals injected both times at proestrus showed no signs of tolerance to LPS after the second injection. Thus, the stages of the estrous cycle both at the time of initial exposure and of re-exposure appear critical in the formation of behavioral tolerance to LPS in rats.
AB - The relations between the estrous cycle, inflammatory responses and the development of tolerance to endotoxin were examined. Female Long-Evans rats were injected intraperitoneally with lipopolysaccharide (LPS; 200 μg/kg) or saline vehicle at 08:00 h on either diestrus (D) or proestrus (P). Ninety-five minutes after injection locomotor activity was assessed in an automated non-novel open-field for 20 min. To assess tolerance development to LPS, rats were re-injected at the next identical stage (i.e. 4 days later; groups: DD, PP) or at the alternate stage (i.e. 6 days later; groups: DP, PD) of the estrous cycle and locomotor activity was again assessed. On Test Day 1 all groups injected with LPS exhibited similar significant activity decrements, regardless of the stage of the estrous cycle. However, on Test Day 2 rats which received both injections of LPS during proestrus (PP) showed no signs of tolerance development, whereas rats in all other groups were tolerant to LPS. In a follow up study, the time between injections was extended to 8 days. Still the animals injected both times at proestrus showed no signs of tolerance to LPS after the second injection. Thus, the stages of the estrous cycle both at the time of initial exposure and of re-exposure appear critical in the formation of behavioral tolerance to LPS in rats.
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U2 - 10.1016/j.psyneuen.2005.11.007
DO - 10.1016/j.psyneuen.2005.11.007
M3 - Article
C2 - 16413135
AN - SCOPUS:33644858621
SN - 0306-4530
VL - 31
SP - 510
EP - 525
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
IS - 4
ER -
