1. ¹Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan, Israel
2. ²The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
3. ³Department of Molecular Biology, Ariel University Center of Samaria Ariel, Ariel, Israel
4. ⁴Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

Correspondence: , The Mina and Everard Goodman Faculty of Life Sciences and Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Geha Road, Ramat-Gan 52900, Israel. Tel: +972 3 531 8123; Fax: +972 3 635 4965; E-mail: Yadidg@mail.biu.ac.il

Received 27 May 2008; Revised 6 August 2008; Accepted 8 August 2008; Published online 8 October 2008.

Abstract

Depressive disorders affect approximately 5% of the population in any given year. Antidepressants may require several weeks to produce their clinical effects. Despite progress being made in this area there is still room and a need to explore additional therapeutic modes to increase treatment effectiveness and responsiveness. Herein, we examined a new method for intervention in depressive states based on deep brain stimulation of the ventral tegmental area (VTA) as a source of incentive motivation and hedonia, in comparison to chemical antidepressants. The pattern of stimulation was fashioned to mimic the firing pattern of VTA neurons in the normal rat. Behavioral manifestations of depression were then monitored weekly using a battery of behavioral tests. The results suggest that treatment with programmed acute electrical stimulation of the VTA substantially alleviates depressive behavior, as compared to chemical antidepressants or electroconvulsive therapy, both in onset time and longitudinal effect. These results were also highly correlated with increases in brain-derived neurotrophic factor mRNA levels in the prefrontal cortex.