Brain-Derived Neurotrophic Factor Produces Antidepressant Effects in Behavioral Models of Depression

TLDR

Antidepressant treatment has been shown to upregulate BDNF expression in the rat hippocampus. This study tested whether hippocampal BDNF induces antidepressant effects in learned helplessness and forced swim test models. A single bilateral BDNF infusion into the hippocampal dentate gyrus produced rapid, sustained antidepressant‑like effects in LH and FST comparable to systemic antidepressants, with similar effects from NT‑3 but not NGF, and no impact on locomotion or passive avoidance, supporting BDNF’s role in antidepressant action.

Abstract

Previous studies demonstrated that antidepressant treatment increases the expression of brain-derived neurotrophic factor (BDNF) in rat hippocampus. The present study was conducted to test the hypothesis that BDNF in the hippocampus produces an antidepressant effect in behavioral models of depression, the learned helplessness (LH) and forced swim test (FST) paradigms. A single bilateral infusion of BDNF into the dentate gyrus of hippocampus produced an antidepressant effect in both the LH and FST that was comparable in magnitude with repeated systemic administration of a chemical antidepressant. These effects were observed as early as 3 d after a single infusion of BDNF and lasted for at least 10 d. Similar effects were observed with neurotrophin-3 (NT-3) but not nerve growth factor. Infusions of BDNF and NT-3 did not influence locomotor activity or passive avoidance. The results provide further support for the hypothesis that BDNF contributes to the therapeutic action of antidepressant treatment.