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.

[1]  K. Shieh,et al.  Depression- and anxiety-like behaviors of a rat model with absence epileptic discharges , 2009, Neuroscience.

[2]  D. Fuller,et al.  BDNF is necessary and sufficient for spinal respiratory plasticity following intermittent hypoxia , 2004, Nature Neuroscience.

[3]  Steven W. Johnson,et al.  Synaptic plasticity in rat subthalamic nucleus induced by high‐frequency stimulation , 2003, Synapse.

[4]  T. Robbins,et al.  Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates , 2004, Neuroscience & Biobehavioral Reviews.

[5]  Mark Hallett,et al.  A Coil Design for Transcranial Magnetic Stimulation of Deep Brain Regions , 2002, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[6]  A. Zangen,et al.  Knockdown of brain-derived neurotrophic factor in specific brain sites precipitates behaviors associated with depression and reduces neurogenesis , 2009, Molecular Psychiatry.

[7]  E. Nestler,et al.  The Mesolimbic Dopamine Reward Circuit in Depression , 2006, Biological Psychiatry.

[8]  V. Rotenberg,et al.  Functional brain asymmetry as a determinative factor in the treatment of depression: Theoretical implications , 2008, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[9]  Eric J. Nestler,et al.  The molecular neurobiology of depression , 2008, Nature.

[10]  R. Duman,et al.  A Role for MAP Kinase Signaling in Behavioral Models of Depression and Antidepressant Treatment , 2007, Biological Psychiatry.

[11]  M Hallett,et al.  Mood improvement following daily left prefrontal repetitive transcranial magnetic stimulation in patients with depression: a placebo-controlled crossover trial. , 1997, The American journal of psychiatry.

[12]  S. Rauch,et al.  Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Treatment-Resistant Depression , 2009, Biological Psychiatry.

[13]  A. Grace,et al.  Glutamatergic Afferents from the Hippocampus to the Nucleus Accumbens Regulate Activity of Ventral Tegmental Area Dopamine Neurons , 2001, The Journal of Neuroscience.

[14]  Andrew Lemire,et al.  Electroconvulsive Seizures Regulate Gene Expression of Distinct Neurotrophic Signaling Pathways , 2004, The Journal of Neuroscience.

[15]  P. Willner,et al.  Suppression of sucrose drinking by chronic mild unpredictable stress: A methodological analysis , 1992, Neuroscience & Biobehavioral Reviews.

[16]  M. Witter,et al.  Organization of the projections from the subiculum to the ventral striatum in the rat. A study using anterograde transport of Phaseolus vulgaris leucoagglutinin , 1987, Neuroscience.

[17]  F. Fregni,et al.  Can the 'yin and yang' BDNF hypothesis be used to predict the effects of rTMS treatment in neuropsychiatry? , 2008, Medical hypotheses.

[18]  Michael X. Cohen,et al.  Deep Brain Stimulation to Reward Circuitry Alleviates Anhedonia in Refractory Major Depression , 2008, Neuropsychopharmacology.

[19]  R. Duman,et al.  Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[20]  J. Huston,et al.  The role of cortical serotonin in anxiety and locomotor activity in Wistar rats. , 2009, Behavioral neuroscience.

[21]  A. Zangen,et al.  Repeated Electrical Stimulation of Reward-Related Brain Regions Affects Cocaine But Not “Natural” Reinforcement , 2007, The Journal of Neuroscience.

[22]  Robert P. Vertes,et al.  Interactions among the medial prefrontal cortex, hippocampus and midline thalamus in emotional and cognitive processing in the rat , 2006, Neuroscience.

[23]  M. Mattson,et al.  Glutamate and Neurotrophic Factors in Neuronal Plasticity and Disease , 2008, Annals of the New York Academy of Sciences.

[24]  M. Barrot,et al.  Brain-derived neurotrophic factor in the ventral midbrain–nucleus accumbens pathway: a role in depression , 2003, Biological Psychiatry.

[25]  D. S. Zahm,et al.  The patterns of afferent innervation of the core and shell in the “Accumbens” part of the rat ventral striatum: Immunohistochemical detection of retrogradely transported fluoro‐gold , 1993, The Journal of comparative neurology.

[26]  P. Mitchell,et al.  A review of the efficacy of transcranial magnetic stimulation (TMS) treatment for depression, and current and future strategies to optimize efficacy. , 2005, Journal of affective disorders.

[27]  Spartaco Santi,et al.  Induction of long-term potentiation and depression is reflected by corresponding changes in secretion of endogenous brain-derived neurotrophic factor. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Abraham Zangen,et al.  A randomized controlled feasibility and safety study of deep transcranial magnetic stimulation , 2007, Clinical Neurophysiology.

[29]  L. Carpenter.  Neurostimulation in resistant depression , 2006, Journal of psychopharmacology.

[30]  P. Fitzgerald,et al.  Repetitive Transcranial Magnetic Stimulation for Major Depressive Disorder: A Review , 2008 .

[31]  Eric Bardinet,et al.  Distinct striatal targets in treating obsessive-compulsive disorder and major depression. , 2009, Journal of neurosurgery.

[32]  J. Price,et al.  The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. , 2000, Cerebral cortex.

[33]  S H Lisanby,et al.  Animal models of the mechanisms of action of repetitive transcranial magnetic stimulation (RTMS): Comparisons with electroconvulsive shock (ECS) , 2000, Depression and anxiety.

[34]  M. Fava,et al.  DEFINITION AND RESISTANT DEPRESSION EPIDEMIOLOGY OF TREATMENT , 1996 .

[35]  Serge Nef,et al.  Brain-Derived Neurotrophic Factor Conditional Knockouts Show Gender Differences in Depression-Related Behaviors , 2007, Biological Psychiatry.

[36]  P. Sachdev,et al.  Chronic repetitive transcranial magnetic stimulation is antidepressant but not anxiolytic in rat models of anxiety and depression , 2005, Psychiatry Research.

[37]  P. Willner.  Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation , 1997, Psychopharmacology.

[38]  J. Huse,et al.  Yin and yang: Cancer-implicated miRNAs that have it both ways , 2009, Cell cycle.

[39]  M. Paula-Barbosa,et al.  Selective loss of hilar neurons and impairment of initial learning in rats after repeated administration of electroconvulsive shock seizures , 2003, Experimental Brain Research.

[40]  C. Bramham,et al.  BDNF function in adult synaptic plasticity: The synaptic consolidation hypothesis , 2005, Progress in Neurobiology.

[41]  R. Duman,et al.  Pathophysiology of depression: the concept of synaptic plasticity , 2002, European Psychiatry.

[42]  M. Delgado,et al.  Reward‐Related Responses in the Human Striatum , 2007, Annals of the New York Academy of Sciences.

[43]  P. Willner,et al.  Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant , 2004, Psychopharmacology.

[44]  A. Pitkänen,et al.  Projections from the lateral, basal, and accessory basal nuclei of the amygdala to the hippocampal formation in rat , 1999, The Journal of comparative neurology.

[45]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[46]  A. Grace,et al.  High-Frequency Deep Brain Stimulation of the Nucleus Accumbens Region Suppresses Neuronal Activity and Selectively Modulates Afferent Drive in Rat Orbitofrontal Cortex In Vivo , 2007, The Journal of Neuroscience.

[47]  Olga V. Demler,et al.  The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). , 2003, JAMA.

[48]  Humberto Nicolini,et al.  A Patient with a Resistant Major Depression Disorder Treated with Deep Brain Stimulation in the Inferior Thalamic Peduncle , 2005, Neurosurgery.

[49]  M. Papp,et al.  Decreased hedonic responsiveness following chronic mild stress is not secondary to loss of body weight , 1996, Physiology & Behavior.

[50]  A. Zangen,et al.  Automated behavioral analysis of limbs’ activity in the forced swim test , 2009, Journal of Neuroscience Methods.

[51]  C. Zarate,et al.  Ketamine and the next generation of antidepressants with a rapid onset of action. , 2009, Pharmacology & therapeutics.

[52]  A. Lozano,et al.  Deep Brain Stimulation for Treatment-Resistant Depression , 2005, Neuron.

[53]  Leor N. Katz,et al.  Deep transcranial magnetic stimulation over the prefrontal cortex: Evaluation of antidepressant and cognitive effects in depressive patients , 2009, Brain Stimulation.

[54]  A. Zangen,et al.  Age‐dependent effects of chronic stress on brain plasticity and depressive behavior , 2008, Journal of neurochemistry.

[55]  Ruoyan Chen,et al.  Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain , 2003, Biological Psychiatry.

[56]  M. Hallett,et al.  Transcranial magnetic stimulation of deep brain regions: evidence for efficacy of the H-Coil , 2005, Clinical Neurophysiology.

[57]  P. Girardi,et al.  Repeated electroconvulsive stimulation impairs long-term depression in the neostriatum , 2004, Biological Psychiatry.

[58]  Paul Leonard Gabbott,et al.  Prefrontal cortex in the rat: Projections to subcortical autonomic, motor, and limbic centers , 2005, The Journal of comparative neurology.

[59]  J. Bergado,et al.  Opposite effects of shell or core stimulation of the nucleus accumbens on long-term potentiation in dentate gyrus of anesthetized rats , 2008, Neuroscience.

[60]  R. Morris.  Developments of a water-maze procedure for studying spatial learning in the rat , 1984, Journal of Neuroscience Methods.

[61]  C. Junqué,et al.  Subtypes of Memory Dysfunction Associated with ECT: Characteristics and Neurobiological Bases , 2001, The journal of ECT.