Study Of Animal Experiment And Mechanism About Deep Brain Stimulation Of The Lateral Habenula In Treatment For Depressive Disorder

Objectives: Depression is a common psychologic obstacle and a chronic disease with high mutilation rate . Prevalence rate is about 3% to 8%. The main clinical manifestations are significant and lasting depression, with persistent fatigue and diminished energy, insomnia, anxiety, irritability, loss of appetite and weight changes, and so seriously, and even hallucinations, delusions, and suicide. Depressive disorder is chronic disease, with high morbidity and shows the trend of increasing prevalence in recent years. World Health Organization predicts that depression , cancer, and AIDS will became the three major diseases of human health hazards in the 21th century. The incidence of depression is resulted by biological, psychological and social interaction. The treatment is mainly pharmacological treatment and psychological therapy. However, with sufficient quantities and course of at least two different mechanisms of antidepressant medications ,some patients still have no response. That is refractory depression. For these patients, looking for a new and effective treatment is urgent problems of clinicians.Deep brain stimulation, often referred to as "brain pacemaker", is the implantable device. It can stimulat the specific sites of brain deepiy to provide continuous pulse, which si so-called deep brain stimulation (deep brainstimulation, DBS).By selecting the electrode stimulation parameters, including stimulation pulse amplitude, frequency and width , it can get the best efficacy with minimal side effects. In the past few decades, deep brain stimulation has become a highly effective surgical treatment in refractory movement disorders including dystonia, essential tremor and Parkinson's disease from a high degree of experimental methods. because the DBS has the similar clinical effects with operation damaging the same nucleus .The experiment embedded the stimulating electrode in the lateral habenular nucleus accurately, comparing of its antidepressant effect, to identify that the high-frequency stimulation of the lateral habenular nucleus can improve depressive symptoms of rat model of depression,whose mechanism is increaseing the monoamine neurotransmitters in rat model of depression, to provide a new target and theoretical basis for the clinical treatment of deep brain stimulation of refractory depression .Methods: As chronic unpredictable mild stress rat model of depression method,,the rats had a mild unpleasant stress every day in 4 weeks,such as cold water swimming, thermal environment, day and night reversed, clipping tail, shocking in the level, fasting, prohibition of water.Every day a stimulus, each stimulus is not in the form of a continuous 2 days , forming a mild unpredictable stress,to avoid animals adapting to the same stimuli. Viewing spontaneous exploratory behavior exercise capacity, the sugar intake of rats in the open field test, and determining whether is the model or not. On the use of stereotactic stimulation, electrodes were implanted to high-frequency stimulate the target lateral habenular nucleus, to refain the activities of the lateral habenular nucleus,to observe the changes in animal behavior before and after stimulation, confirming that the lateral habenular nucleus after high-frequency stimulation can improve the performance of rats with depression. Using fluorescence determination to determine the brain tissue and blood monoamine neurotransmitters (serotonin, dopamine, norepinephrine) content of high-frequency stimulation 7d , group 13d group ,21d group, 28d group, sham stimulation group, control group, depression model rat and and compare ,to Confirm that after high-frequency stimulat the lateral habenular nucleus can increase brain and blood levels of monoamine neurotransmitters, and it had the cumulative effect of time, to makesure its effect of treatment.Result: By comparing the behavior of model rats ,we can find reduce significantly in 3min after the level of movement and vertical movement . And contents of monoamine neurotransmitters of the depression model group decreased than the normal rats. Comparing the change of the behavior and monoamine neurotransmitter levels of stimulated rats, we can find that Deep brain stimulation lateral habenular nucleus can improve the depressive symptoms of rat, and have the role in the treatment of depression in rats. And its mechanism is increasing the brain and blood levels of monoamine neurotransmitters in rat in order to achieve therapeutic purposes. Also showing the relationship between time and stimulation: to stimulate the longer, the treatment the better.Conclusions:(1) Habenular nucleus changes the most obviously in the brain of animal models of depression ,and is one of representative of areas in the brain of depression .(2) High-frequency stimulation of the lateral habenular nuclear of animal models of depression can significantly remission symptoms of depression, to provide the new stimulus target for the clinical treatment of deep brain stimulation of refractory depression.