Site-specific antidepressant effects of repeated subconvulsive electrical stimulation: potential role of brain-derived neurotrophic factor.
BACKGROUND
Electroconvulsive therapy (ECT) is a very effective treatment for major depression. This method involves robust nonfocal stimulation of the brain and can normalize both neurochemical alterations and depressive behavior in animal models. We hypothesized that short stimulation sessions of specific reward-related brain sites might induce similar effects.


METHODS
In the present study we compared behavioral and neurochemical effects produced by ECT and by repeated stimulation of reward-related brain sites, in a widely used rat model for depressive behavior induced by chronic mild stress (CMS). Different groups of rats received 10 sessions of either electroconvulsive shocks or subconvulsive electrical stimulation (SCES) of specific brain sites with an implanted electrode. The SCES temporal parameters were similar to those used in transcranial magnetic stimulation studies in humans. A battery of behavioral tests and measurements of brain-derived neurotrophic factor (BDNF) levels were used to assess the effectiveness of these treatments relative to sham treatments.


RESULTS
Repeated SCES of either the nucleus accumbens (NAC) or the ventral but not the dorsal prelimbic cortex (PLC) reversed the main behavioral deficit and the reduction of BDNF levels in the hippocampus that were induced by CMS. The ECT was more effective because it also normalized a behavioral deficit associated with anxiety but produced a learning and memory impairment.


CONCLUSIONS
This study implicates the ventral PLC and the NAC in the pathophysiology of depressive behavior and suggests that local intermittent SCES can induce an antidepressant effect similar to that of ECT, without the cognitive impairment caused by the convulsive treatment.
Gersner
Roman
R
Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
Toth
Erika
E
Isserles
Moshe
M
Zangen
Abraham
A
D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002540:Cerebral Cortex / Q000502:physiology; D003863:Depression / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D004565:Electroconvulsive Therapy / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005106:Exploratory Behavior / Q000502:physiology; D005518:Food Preferences / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism; D008124:Locomotion / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009714:Nucleus Accumbens / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000150:complications; D013395:Sucrose / Q000008:administration & dosage; D013549:Sweetening Agents / Q000008:administration & dosage; D013550:Swimming / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D013549:Sweetening Agents; D013395:Sucrose