Drug development research has identified neurotrophic factors as a downstream target of chronic antidepressant treatments. In order to study their antidepressant-like effects, two neurotrophic factors, brain-derived neurotrophic factor and insulin-like growth factor I, were examined in the rat modified forced swimming test after a single icv administration. Both neurotrophins produced antidepressant-like behavioral effects in the modified rat forced swimming test, reducing immobility and increasing swimming. In contrast to currently used antidepressants, which produce acute effects in the forced swimming test, the effects of the neurotrophins were unusually long lasting and persisted at least 6 days after the treatment. Neither neurotrophic factor had an effect on locomotor activity. The results support a role for neurotrophic factors mediating the behavioral effects of antidepressant drugs.