The maternal and developmental toxicity of combined exposure to restraint s
tress and caffeine was assessed in mice. On Day 9 of gestation, six groups
of pregnant mice were treated (p.o.) with a single dose of 30, 60, or 120 m
g/kg of caffeine. Immediately after caffeine administration, three of these
groups were subjected to restraint for 14 hr. Control groups included unre
strained and restrained pregnant mice not exposed to caffeine. An additiona
l group of animals (unrestrained and not exposed to caffeine) was deprived
of food for 14 hr. A two-way (caffeine dose x restraint) analysis of varian
ce revealed an overall effect (reduction) of restraint end caffeine exposur
e on maternal body weight gain and food consumption on gestation Days 9-11.
Significant reductions were also observed in body weight at termination an
d corrected body weight change of dams concurrently exposed to 120 mg/kg of
caffeine and restraint. By contrast, no significant effects of caffeine, r
estraint, or caffeine plus restraint on embryo/fetal development were noted
. The doses of caffeine administered here are much higher than those usuall
y consumed by the general population. Under the current experimental condit
ions, caffeine alone or combined with restraint stress was not embryotoxic
or teratogenic in mice.