Programmed acute electrical stimulation of ventral tegmental area alleviates depressive-like behavior.
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.
Friedman
Alexander
A
Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan, Israel.
Frankel
Michael
M
Flaumenhaft
Yakov
Y
Merenlender
Avia
A
Pinhasov
Albert
A
Feder
Yuval
Y
Taler
Michal
M
Gil-Ad
Irit
I
Abeles
Moshe
M
Yadid
Gal
G
D000200:Action Potentials; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D046690:Deep Brain Stimulation; D003863:Depression / Q000628:therapy*; D005106:Exploratory Behavior / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012646:Self Administration; D012919:Social Behavior; D013395:Sucrose / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000502:physiology*
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D013395:Sucrose