Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation

This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson's disease, Huntington's disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms.     

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.     

Real-Time Assessments of Dopamine Function during Behavior: Single-Unit Recording, Iontophoresis, and Fast-Scan Cyclic Voltammetry in Awake, Unrestrained Rats

Although ample evidence implicates the dopamine (DA) projection to the neostriatum and nucleus accumbens in motor and motivational processes, relatively little information is available on how DA alters neostriatal or accumbal functions under naturally occurring behavioral conditions. Further insight into neuron-behavior relationships can be achieved with the application of single-unit recording techniques, including iontophoresis and fast-scan cyclic voltammetry (FSCV), to awake, unrestrained animals. Single-unit recording has revealed that amphetamine, a widely abused psychomotor stimulant, activates motor-, but inhibits nonmotor-related neurons in neostriatum and nucleus accumbens. Although either response can be blocked by DA receptor antagonists, the amphetamine-induced activation also depends on an intact corticostriatal system, suggesting a role for glutamate (GLU). Both neostriatal and accumbal neurons are sensitive to iontophoretic application of either DA or GLU, but when applied during low-dose application of DA, the GLU signal is enhanced relative to background activity. In effect, DA appears to modulate GLU by strengthening the GLU signal-to-noise ratio. To assess DA release under behaviorally relevant conditions, FSCV has been used to obtain real-time measurements of DA efflux in a free-choice novelty test. DA efflux increased only during the brief period of entry into novelty, and the increase was confined to accumbal shell and the shell-core transition zone, the so-called shore. Neither accumbal core nor the overlying neostriatum showed a novelty-related DA change. Thus, DA release during behavior is not uniform and in the case of novelty appears targeted to the limbic-related area of accumbal shell. Further application of these and other in vivo technologies to ambulant animals is required to identify the complex mechanisms underlying both the release of DA and its effect on neostriatal and accumbal neurons during behavior.     

Effects of tianeptine on 5-hydroxyindoles and on the morphine-induced increase in 5-HT metabolism at the medullary dorsal horn level as measured by in vivo voltammetry in freely moving rats

The present study, by the use of in vivo electrochemical detection of 5-hydroxyindole (peak ‘3’) in the bulbo spinal serotonergic system at the medullary dorsal horn (MDH) level, investigated the effects of the new tricyclic antidepressant (TCA) tianeptine, which has been shown to be a specific serotonin (5-HT) uptake enhancer. It was found that acutely administered tianeptine (10 mg/kg, i.p.) induced a marked significant increase in peak 3 within the dorsal horn, an in vivo observation which is in accordance with the biochemical properties of tianeptine as studied in forebrain structures. In addition, the effect of tianeptine on the morphine-induced increase in 5-HT metabolism was investigated, by comparison with the previous data obtained with the specific 5-HT uptake inhibitor femoxetine in the MDH. It was shown that tianeptine can display additive effect with morphine (10 mg/kg, i.p.) on 5-HT metabolism at the MDH level. These results are discussed in relation to the effects of classical TCAs and the particular properties of tianeptine.     

Electrochemical, quantum-chemical and antioxidant properties of antipyrine and its derivatives

Electrochemical, quantum-chemical and antioxidant properties of antipyrine and its derivatives have been investigated in this work.

New quantum-chemical parameter such as difference of formation heats of a molecule and its cation radical (ΔΔH_cat) has been used in order to describe properties of the investigated substances. Electrochemical properties (oxidation, reduction potentials) have been investigated. Correlation between the calculated ΔΔH_cat and the experimentally obtained oxidation potentials for antipyrine and its derivatives has been found.     

Phenol and para-substituted phenols electrochemical oxidation pathways

The electrochemical behaviour of phenol, catechol, hydroquinone, resorcinol, dopamine, and para-substituted phenolic compounds, 4-ethylphenol, tyrosine, and tyramine, was studied over a wide pH range using a glassy carbon electrode. The oxidation of phenol is pH dependent and irreversible, occurring in one step, and followed by hydrolyse in ortho- and para-positions, leading to two oxidation products, catechol and hydroquinone. The oxidation of phenol oxidation products, ortho-phenol and para-phenol, is reversible and pH dependent. The oxidation potential of para-substituted phenols varies slightly due to their substituent group in position C4, and occurs in one oxidation step corresponding to the oxidation of phenol. The oxidation products of this group of para-substituted phenols are reversibly oxidised and adsorb on the electrode surface.     

Voltammetry and surface analysis of AISI 316 stainless steel in chloride-containing simulated concrete pore environment

The study of passive layers grown on AISI 316 stainless steel in solutions that simulate concrete pore environments contaminated with Cl^? is presented. Model solutions of saturated Ca(OH)₂ and cement extract (CE) with and without the addition of 5 g/L of NaCl are compared. Cyclic voltammetry (CV) shows different electrochemical responses of passive layers grown on samples immersed in these solutions under open circuit potential (ocp). A more resistive passive film was found on the samples exposed to the CE solution. The different voltammetric responses suggest differences in composition of the passive layers formed on each solution. XPS spectra confirm the dissimilarity in atomic composition. Optical microscope images and AFM images of the pits formed on the samples illustrate the differences of AISI 316 surface topography after exposure to model solutions. Because of these differences, it is recommended to use CE solution as a model solution and ocp passivation to simulate concrete environments.     

Asenapine, a novel psychopharmacologic agent: preclinical evidence for clinical effects in schizophrenia

Rationale Asenapine is a novel psychopharmacologic agent being developed for the treatment of schizophrenia and bipolar disorder. Materials and methods The present study was undertaken to investigate the effects of asenapine using animal models predictive of antipsychotic efficacy (conditioned avoidance response [CAR]) and extrapyramidal side effects (EPS; catalepsy). In parallel, the effects of asenapine on regional dopamine output using in vivo microdialysis in freely moving rats, dopamine output in the core and shell subregions of nucleus accumbens (NAc) using in vivo voltammetry in anesthetized rats, and N-methyl-d-aspartate (NMDA)-induced currents in pyramidal neurons of the medial prefrontal cortex (mPFC) using the electrophysiological technique intracellular recording in vitro were assessed. Results Asenapine (0.05–0.2 mg/kg, subcutaneous [s.c.]) induced a dose-dependent suppression of CAR (no escape failures recorded) and did not induce catalepsy. Asenapine (0.05–0.2 mg/kg, s.c.) increased dopamine efflux in both the mPFC and the NAc. Low-dose asenapine (0.01 mg/kg, intravenous [i.v.]) increased dopamine efflux preferentially in the shell compared to the core of NAc, whereas at a higher dose (0.05 mg/kg, i.v.), the difference disappeared. Finally, like clozapine (100 nM), but at a considerably lower concentration (5 nM), asenapine significantly potentiated the NMDA-induced responses in pyramidal cells of the mPFC. Conclusions These preclinical data suggest that asenapine may exhibit highly potent antipsychotic activity with very low EPS liability. Its ability to increase both dopaminergic and glutamatergic activity in rat mPFC suggests that asenapine may possess an advantageous effect not only on positive symptoms in patients with schizophrenia, but also on negative and cognitive symptoms.     

Voltammetric and XPS investigations of nickel hydroxide electrochemically dispersed on gold surface electrodes

A chemically modified electrode composed of mixed hydroxide and oxyhydroxide nickel film (6–8 nmol cm^?2) on the gold substrate (Au ∣ Ni) was characterized by cyclic voltammetry and XPS techniques. The gold substrate electrodes were firstly electrochemically conditioned in 0.2 M NaOH by cycling the potential between ?0.25 and 0.6 V versus SCE, then modified by cathodic electrodeposition of nickel hydroxide films. These nickel films were obtained either by voltage cycling (50 mV s^?1) between 0.0 and ?0.5 V (SCE) or at constant potential of ?0.3 or ?0.5 V using non-deaerated 50 mM Ni(NO₃)₂ solutions. X-ray photoelectron spectroscopy (XPS) characterisation and voltammetric behaviour of Au ∣ Ni electrodes in alkaline solutions are described. Continuous electrochemical cycling of the Au ∣ Ni electrodes induces significant changes of the nickel films in terms of crystallographic structures and chemical composition. Combination of XPS and electrochemical methodologies have demonstrated the ability to follow the morphological and chemical changes in alkaline solutions upon cycling potentials. Angular-dependent XPS measurements have demonstrated that electrochemical treatment induces the formation of a uniform film layer with the following chemical distribution: Au ∣ Ni(OH)₂ ∣ NiOOH. The electrocatalytic activity of the Au ∣ Ni electrodes is investigated in alkaline medium using glucose as a model compound. The favourable combination of active species such as gold and nickel leads to a sensing electrode with strong catalytic activity over a wide range of applied potentials.