Deep brain stimulation, vagal nerve stimulation and transcranial stimulation: An overview of stimulation parameters and neurotransmitter release

Neurological disorders are among the most challenging medical problems faced by science today. To treat these disorders more effectively, new technologies are being developed by reviving old ideas such as brain stimulation. This review aims to compile stimulation techniques that are currently in use to explore or treat neurological disorders. Transcranial magnetic stimulation is a non-invasive method of modulating neuronal activity with induced electric currents. Other more invasive methods, such as deep brain stimulation and vagal nerve stimulation, use implanted probes to introduce brain activity alterations. Scientific and clinical applications have largely preceded the development of extensive animal models, presenting a challenge for researchers. This has left researchers with information on alleviating symptoms in humans but without solid research as to the mechanisms and neurobiological effects of the devices. This review combines stimulation parameters developed in animal models and stimulation techniques used in human treatment; thus, resulting in a greater understanding of the mechanisms and neurobiological effects of neuromodulation devices.     

Real-time voltammetric detection of cocaine-induced dopamine changes in the striatum of freely moving mice

In the present voltammetric study, we have characterized cocaine-induced changes in evoked dopamine release and uptake in the striatum of freely moving mice in real time. Cocaine induced marked dopamine uptake inhibition measured as apparent K_m changes, producing a maximal effect 20 min following a single injection (15 mg/kg, i.p.). Changes in uptake were paralleled by increases in evoked dopamine release per stimulus pulse, revealing a high correlation between these two parameters following cocaine administration. This initial characterization of cocaine effects on striatal dopamine transmission in the commonly used C57BL/6 mouse strain provides a basis for future voltammetric studies using genetic mouse models.     

Aspartame decreases evoked extracellular dopamine levels in the rat brain: an in vivo voltammetry study

Conflicting reports exist concerning the effect aspartame (APM, l-aspartyl-l-phenylalanine methyl ester) has upon brain biogenic amines. In the following study, in vivo voltammetry was utilized to measure evoked extracellular dopamine (DA) levels in the striatum of rats in order to assess APM's effect. Time-course experiments revealed a significant decline in evoked extracellular DA levels within 1 h of a single systemic dose (500 mg/kg i.p.) when compared to vehicle-injected controls. The effect was frequency dependent and showed a significant decrease utilizing high frequency stimulation parameters (50 and 60 Hz). In order to further determine APM's potential to alter evoked extracellular DA levels, extended stimulation periods were employed to deplete releasable stores both before and after APM administration in intact and 6-OHDA partially lesioned animals. The extended stimulation periods were applied at 60 Hz for 2,5,10 and 20 s durations. APM decreased DA levels under these conditions in both intact and 6-OHDA partially lesioned animals by an average of 34% and 51%, respectively. Kinetic analysis performed on frequency series indicated that the diminished DA levels corresponded to a significant reduction in DA release. These findings suggest that APM has a relatively potent effect of decreasing evoked extracellular DA levels when administered systemically under the conditions specified.     

Effects of chronic alcohol exposure on dopamine uptake in rat nucleus accumbens and caudate putamen

Rationale

Existing data strongly suggest that alcohol affects dopamine (DA) neurotransmission in the brain. However, many questions remain about the effects of alcohol on the delicate equilibrium between such neurochemical processes as DA release and uptake. Dysregulation of these processes in the mesolimbic and nigrostriatal systems after chronic alcohol ingestion could be a neuroadaptation contributing to dependence.

Objectives

In the present study, we have employed an alcohol vapor inhalation model to characterize the effects of chronic alcohol exposure on DA dynamics in rat nucleus accumbens (NAc) and caudate putamen (CP) using fast-scan cyclic voltammetry (FSCV) in brain slices. This method provides a unique view of real-time, spatially resolved changes in DA concentration.

Results

We found that chronic alcohol exposure enhanced DA uptake rates in rat NAc and CP. These changes would have the effect of down-regulating extracellular DA levels, presumably a compensatory effect related to increased DA release by repeated alcohol exposure. The sensitivity of terminal release-regulating DA autoreceptors was not different in alcohol-exposed rats compared with alcohol-naïve animals.

Conclusions

The DA uptake changes after chronic alcohol exposure documented here using FSCV may be associated with a compensatory response of the DA system aimed at decreasing DA signaling. Alterations in autoreceptor function may require relatively long lasting alcohol exposure.

     

Adderall<Superscript>®</Superscript> produces increased striatal dopamine release and a prolonged time course compared to amphetamine isomers

Rationale

Adderall^® is currently used for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD) and is composed of a novel mixture of approximately 24% l-amphetamine and 76% d-amphetamine salts. There are, however, no investigations of the pharmacological effects of this combination in vivo.

Objectives

The technique of high-speed chronoamperometry using Nafion^®-coated single carbon-fiber microelectrodes was used to study amphetamine-evoked dopamine (DA) release produced by Adderall^®, d-amphetamine, or d,l-amphetamine in the striatum of anesthetized male Fischer 344 (F344) rats. The amphetamine solutions were locally applied from micropipettes by pressure ejection.

Results

Local applications of Adderall^® resulted in significantly greater DA release signal amplitudes with prolonged time course of dopamine release and re-uptake as compared to d-amphetamine and d,l-amphetamine.

Conclusions

These data support the hypothesis that the combination of amphetamine enantiomers and salts in Adderall^® has effects on DA release, which result in increased and prolonged DA release, compared to d- and d,l-amphetamine.

     

Impaired dopamine release and uptake in R6/1 Huntington's disease model mice

Huntington's disease (HD) is a progressive, neurodegenerative movement disorder. Here, we used fast-scan cyclic voltammetry to measure dopamine release and uptake in striatal brain slices from R6/1 HD model mice. Peak dopamine release ([DA]_max) was significantly diminished in R6/1 mice (52% of wild-type at 24 weeks of age). Similarly, dopamine released per locally applied electrical stimulus pulse ([DA]_p), which is [DA]_max corrected for uptake and electrode performance, was also diminished in R6/1 mice (43% of wild-type by 24 weeks of age). Moreover, V_max, the maximum rate of dopamine uptake, obtained by modeling the stimulated release plots, was decreased at 16 and 24 weeks of age in R6/1 mice (51 and 48% of wild-type, respectively). Thus, impairments in both dopamine release and uptake appear to progress in an age-dependent manner in R6/1 mice.     

Electrochemical and Raman spectroscopic studies of the effect of lanthanide ions on the activity of mitochondrial malate dehydrogenase

Chronoamperometry based on the ‘diffusion’ layer concept of the convective system was used to assay the activity of mitochondrial malate dehydrogenase (MDH). When the enzyme-catalysed reaction was initiated by adding the enzyme MDH into a well-stirred nicotinamide adenine dinucleotide (NADH, coenzyme) solution, the enzyme activity could be indicated by the continuous in-situ decrease in the limiting steady-state oxidation current of NADH. The effects of some lanthanide ions on the MDH activity were monitored. The La³⁺, Ce³⁺ and Eu³⁺ ions could activate markedly the enzyme MDH as the concentrations were lower. The activation mechanism would be that the lanthanide ions could interrupt the binding of NAD⁺ to MDH by combining preferentially to NAD⁺. This mechanism was proposed on the basis of voltammetric and Raman spectroscopic studies.     

Electrochemical study of copper and iron compounds in the solid state by using voltammetry of immobilized microparticles: application to copper ferrite characterization

The electrochemical behaviour of different solid samples, such as Cu₂O_(s), CuO_(s), Fe₂O_3(s), Fe₃O_4(s) and their binary mixtures, has been studied using the voltammetry of immobilised microparticles technique. These studies were carried out by using an electrode with a glassy tube and a plastic piston, containing a mass of carbon paste bound with liquid paraffin. The voltammograms obtained were utilised for the characterization of the copper ferrites Cu_0.5Fe_2.5O₄, Cu_0.7Fe_2.3O₄, and CuFe₂O₄.     

Permissive role of glucocorticoids on interleukin-1 activation of the hypothalamic serotonergic system

The present study analyses the effect of IL-1β (10 ng i.c.v.) on the hypothalamic serotonergic system and the modulatory role of glucocorticoids. Changes in the serotonin metabolite 5-hydroxyindolacetic acid (5-HIAA) were recorded in freely moving rats by in vivo voltammetry using chronically implanted carbon fiber electrodes (8 μm) in the medial preoptic area. IL-1β induced a dual increase in 5HIAA levels: a rapid, short-term rise was followed by a lasting increase possibly due to newly synthesized IL-1. The synthetic glucocorticoid dexamethasone (DEX, 3 mg/kg i.p., 30 min before IL-1β), prevented the effect of IL-1β starting from 150 min, suggesting that it only inhibited the second increase. In adrenalectomized rats IL-1β had no effect but when these rats were given DEX (40 μg/kg a day for 3 days) the short-term increase was restored. The glucocorticoid receptor antagonist RU38486 (25 mg/kg s.c., 60 min before IL-1β) completely prevented IL-1β activation of the serotonergic system. The results indicate that the glucocorticoids are effective inhibitors of IL-1 synthesis but that they play a permissive role on IL-1β induced activation of the serotonergic system.     

电化学方法研究环丙沙星及其镁、锰络合物与脱氧核糖核酸的相互作用

用电化学的方法,研究环丙沙星(CPFX)及其镁、锰络合物与脱氧核糖核酸(DNA)的相互作用及其极谱伏安行为。结果在0.1mol·L^-1NH₃-NH₄Cl(pH9.2)溶液中,环丙沙星可与DNA作用,产生一新的极谱峰 Ep=-1.72V(vsAg/AgCl),在有Mg²⁺或Mn²⁺存在时则生成三元络合物,产生一电位更负的新峰,峰电位Ep=-1.78V,提示Mg²⁺或Mn²⁺离子参与药物与DNA的作用。对它们的还原峰性质研究表明,电极还原反应是完全不可逆的,电流具有吸附性。本文还探讨了电极还原机理,认为参与电极还原的是三元络合物中的环丙沙星分子,进一步推测CPFX-Mg是嵌入DNA的双螺旋结构中。