Altered brain-derived neurotrophic factor expression in the ventral tegmental area, but not in the hippocampus, is essential for antidepressant-like effects of electroconvulsive therapy.
BACKGROUND
Impaired neuronal plasticity and, specifically, altered expression of brain-derived neurotrophic factor (BDNF) were shown to play a critical role in depressive behavior and the mechanism of various antidepressant treatments including electroconvulsive therapy (ECT). Interestingly, opposing roles were suggested for BDNF in the hippocampus and the ventral tegmental area (VTA), while interactions between these regions were shown on various levels. Here, we evaluated whether BDNF plays an essential role in the antidepressant-like effects of ECT and performed a direct comparison between BDNF manipulations in the VTA and the hippocampus.


METHODS
Knockdown or overexpression of BDNF was induced in hippocampus or VTA of rats by microinjection of specific lentiviral vectors. The effects of these manipulations on antidepressant outcomes of ECT were evaluated by the forced swim test and by sucrose preference measurements, and BDNF expression levels were assessed in other reward-related brain regions.


RESULTS
Here, we show that whereas ECT increased hippocampal BDNF expression, induction of hippocampal BDNF knockdown did not block its antidepressant-like effect. Importantly, we found that ECT caused a robust reduction in VTA BDNF levels. Moreover, VTA BDNF knockdown alone was sufficient to induce an antidepressant-like effect, and VTA BDNF overexpression blocked the antidepressant-like effect of ECT.


CONCLUSIONS
While neuroplastic alterations, as expressed by changes in BDNF expression within different brain regions, are induced by ECT, the antidepressant-like effect of ECT in an animal model depends on reduction of VTA BDNF expression but not on the elevation of hippocampal BDNF expression.
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel; Department of Life Science, Ben Gurion University, Beer Sheva, Israel.
Dekel
D
Taliaz
Vini
V
Nagaraj
Sharon
S
Haramati
Alon
A
Chen
Abraham
A
Zangen
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004565:Electroconvulsive Therapy; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017557:Ventral Tegmental Area / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor