Effects of prenatal exposure to tricyclic antidepressants on adrenergic responses in progeny.

Studies were undertaken to examine the effects on cardiovascular function in progeny of rats treated maternally with the tricyclic antidepressants, doxepin and imipramine. Doxepin was administered once daily during the first trimester (days 1-7), second trimester (days 8-14) or third trimester (days 15-21) of pregnancy, while imipramine was administered during the third trimester only. Exposure to doxepin during the first or second trimester increased infant mortality rate, while third trimester exposure to imipramine, but not doxepin, enhanced infant mortality. Additionally, third trimester imipramine, but not doxepin, exposure reduced birth weight and growth rate of progeny. Tests of cardiac and aortic response to adrenergic stimulation revealed that third trimester exposure to either of these tricyclic antidepressants enhance the responsiveness of the beta-adrenergic system in the aorta, while doxepin exposure during the other trimesters was without effect on aortic beta-response. Prenatal exposure to these antidepressants did not alter blood pressure or the contractile response of aortic tissues to alpha-receptor stimulation. Collectively, these studies reveal that at doses of tricyclic antidepressants which do not cause dysmorphic effects on the fetus, subtle alterations occur in selective adrenergic functions which can persist into adulthood in the rat.