The paradox that experiments in behavioural pharmacology employing nocturna
l rodent species are carried out almost exclusively in the resting phase of
the animals' circadian cycle has remained largely unexamined and unquestio
ned. This is despite the: fact that all major physiological systems in the
body are intrinsically aligned with its natural circadian rhythm. The force
d-swim test (FST) is a rodent model that is used extensively as a screening
test for antidepressant activity. The objectives of the present study were
to examine the behaviour of rats in the FST under diurnal and nocturnal co
nditions and, in addition, to profile the response of neurochemical. neuroe
ndocrine, and cellular indices of stress at time points up to 120 min follo
wing exposure to the FST. The time spent in escape-oriented activity was si
gnificantly Ices: when animals were tested in the dark phase. The profile o
f serum corticosterone and adrenal ascorbic acid concentrations indicates t
hat the animals were less stressed by the test situation juring the active
(i.e., dark) phase of their circadian cycle. Similarly, increases in blood
enzymatic markers of stress-induced cellular damage were less marked follow
ing FST exposure in the nocturnal period. Characteristic stress-induced inc
reases in 5-HT turnover in the frontal cortex and amygdala observed in the
diurnal phase were reversed in the nocturnal period. In conclusion, circadi
an differences in behaviour in the FST may be related to parallel alteratio
ns in the ability of animals to adapt to exposure to stress. (C) 2000 Elsev
ier Science Inc. All rights reserved.