Effects of maternal stress during different gestational periods on the serotonergic system in adult rat offspring.

Pregnant Sprague-Dawley rats were exposed to mild stress treatments during different gestational periods and the offspring were investigated at 60 days of age. In the first study, stress from embryonic day (ED) 11 to ED 20 produced effects similar to those reported following stress throughout pregnancy; increased numbers of 5-HT2 binding sites in cerebral cortex and a reduced intensity of the behavioral syndrome produced by injections of the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). In the second study, stress from ED 3 to ED 14 had no significant effect on the intensity of the 5-MeODMT-elicited 5-HT syndrome while stress from ED 15 to ED 20 had a similar effect as stress throughout pregnancy. These data provide evidence that the critical period for prenatal stress-induced changes in brain 5-HT neurons is between ED 15 and birth. This suggests that the mechanism involves an interaction with developmental events occurring within this time span such as the growth of nerve axons and the formation of synaptic contacts. Our findings also provide further evidence that stress during the final trimester of pregnancy may have serious adverse effects on fetal brain development.