Behavioral effects of perinatal administration of antidepressant drugs in the rat

The monoamine reuptake blockers, imipramine, desipramine, and chlorimipramine, and the monoamine-oxidase inhibitors, iproniazid and isocarboxazid, were administered to pregnant rats (acutely at day 15 of pregnancy, or subchronically from day 10 of pregnancy to the delivery) or to newborn pups (from day 1 to day 5 of life). Prenatal acute injection of the antidepressant drugs failed to modify the development of neonatal reflexes of the rat pups and their adult behavior. Prenatal subchronic administration of the antidepressant drugs was followed by an increase in the number of pups showing neonatal reflexes, but also by an inhibition of the open field behavior and the acquisition of active avoidance responses tested in adulthood. In this respect, monoamine-oxidase inhibitors appeared to be more potent than monoamine reuptake blockers. Furthermore, neonatal administration of all the antidepressant drugs caused an inhibition of the acquisition of active avoidance responses tested in adulthood, but only the monoamine-oxidase inhibitor, isocarboxazid, significantly inhibited also the open field behavior of adult rats. Neither prenatal nor neonatal administration of the antidepressant drugs affected sexual activity of adult rats. The present results suggest that only a prolonged treatment with antidepressant drugs can affect neonatal or adult behavior of the rat, probably through an interference with central monoamine neurotransmission.