scholarly journals Orbitofrontal-striatal potentiation underlies stimulant induced hyperactivity

2019 ◽  
Author(s):  
Sebastiano Bariselli ◽  
Nanami Miyazaki ◽  
Alexxai Kravitz

AbstractStimulants are one of the most widely prescribed classes of pharmaceuticals, but it is unclear which brain pathways underlie their therapeutic and adverse actions. Here, with real-time monitoring of circuit plasticity, we demonstrate that psychostimulants strengthen orbitofrontal (OFC) to dorsomedial striatum (DMS) pathway synapses, and increase striatal output in awake mice. In vivo high-frequency stimulation of OFC-DMS pathway blocked stimulant-induced potentiation and the expression of locomotor sensitization, thereby directly linking OFC-DMS plasticity to hyperactivity.

2007 ◽  
Vol 1162 ◽  
pp. 121-129 ◽  
Author(s):  
Kendall H. Lee ◽  
Katarina Kristic ◽  
Ryan van Hoff ◽  
Frederick L. Hitti ◽  
Charles Blaha ◽  
...  

2010 ◽  
Vol 112 (3) ◽  
pp. 539-548 ◽  
Author(s):  
Young-Min Shon ◽  
Su-Youne Chang ◽  
Susannah J. Tye ◽  
Christopher J. Kimble ◽  
Kevin E. Bennet ◽  
...  

Object The authors of previous studies have demonstrated that local adenosine efflux may contribute to the therapeutic mechanism of action of thalamic deep brain stimulation (DBS) for essential tremor. Real-time monitoring of the neurochemical output of DBS-targeted regions may thus advance functional neurosurgical procedures by identifying candidate neurotransmitters and neuromodulators involved in the physiological effects of DBS. This would in turn permit the development of a method of chemically guided placement of DBS electrodes in vivo. Designed in compliance with FDA-recognized standards for medical electrical device safety, the authors report on the utility of the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for real-time comonitoring of electrical stimulation–evoked adenosine and dopamine efflux in vivo, utilizing fast-scan cyclic voltammetry (FSCV) at a polyacrylonitrile-based (T-650) carbon fiber microelectrode (CFM). Methods The WINCS was used for FSCV, which consisted of a triangle wave scanned between −0.4 and +1.5 V at a rate of 400 V/second and applied at 10 Hz. All voltages applied to the CFM were with respect to an Ag/AgCl reference electrode. The CFM was constructed by aspirating a single T-650 carbon fiber (r = 2.5 μm) into a glass capillary and pulling to a microscopic tip using a pipette puller. The exposed carbon fiber (the sensing region) extended beyond the glass insulation by ~ 50 μm. Proof of principle tests included in vitro measurements of adenosine and dopamine, as well as in vivo measurements in urethane-anesthetized rats by monitoring adenosine and dopamine efflux in the dorsomedial caudate putamen evoked by high-frequency electrical stimulation of the ventral tegmental area and substantia nigra. Results The WINCS provided reliable, high-fidelity measurements of adenosine efflux. Peak oxidative currents appeared at +1.5 V and at +1.0 V for adenosine, separate from the peak oxidative current at +0.6 V for dopamine. The WINCS detected subsecond adenosine and dopamine efflux in the caudate putamen at an implanted CFM during high-frequency stimulation of the ventral tegmental area and substantia nigra. Both in vitro and in vivo testing demonstrated that WINCS can detect adenosine in the presence of other easily oxidizable neurochemicals such as dopamine comparable to the detection abilities of a conventional hardwired electrochemical system for FSCV. Conclusions Altogether, these results demonstrate that WINCS is well suited for wireless monitoring of high-frequency stimulation-evoked changes in brain extracellular concentrations of adenosine. Clinical applications of selective adenosine measurements may prove important to the future development of DBS technology.


2020 ◽  
Vol 44 (3) ◽  
pp. 241-249
Author(s):  
Yoshiaki Omura

While a visiting Professor at the University of Paris, VI (formerly Sorvonne) more than 40 years ago, the Author became very good friends with Dr. Paul Nogier who periodically gave seminars and workshops in Paris. After the author diagnosed his cervical problem & offered him simple help, Dr. Nogier asked the Author to present lectures and demonstrations on the effects of ear stimulation, namely the effects of acupuncture & electrical stimulation of the ear lobules. It is only now, in 2019 that we have discovered 2–5 minute high frequency stimulation of the ear lobule inhibits cancer activity for 1– 4 hours post stimulation. Although the procedure is extremely simple. First take optimal dose of Vitamin D3, which has the most essential 10 unique beneficial factors required for every human cell activity. Next, apply high frequency stimulation to ear lobule while the worst ear lobule is held by all fingers with vibrator directly touching the surface of the worst ear lobule, preferably after patient repeatedly takes optimal dose of Vitamin D3. When the worst ear lobule is held between thumb & index fingers and applying mechanical stimulation of 250 ~ 500 mechanical vibration/second for 2 ~ 5 minutes using an electrical vibrator, there is rapid disappearance of cancer activity in both the brain and rest of the body for short time duration 1 ~ 4 hours. The effect often increases by additional pressure by holding fingers. As of May 2019, the Author found that many people from various regions of the world developed early stages of multiple cancers. For evaluation of this study, U. S. patented Bi-Digital O-Ring Test (BDORT) was used which was developed by the Author while doing his Graduate experimental physics research at Colombia University. BDORT was found to be most essential for determining the beneficial effects as well as harmful effects of any substance or treatment. Using BDORT, Author was the first to recognize severe increasing mid-backache was an early sign of pancreatic cancer of President of New York State Board of Medicine after top pain specialists failed to detect the cause after 3 years of effort, while the BDORT showed early stages of cancer whereas conventional X-Ray of the pancreas did not show any cancer image until 2 months after Author detected with BDORT. For example, the optimal dose of the banana is usually about 2.0 - 2.5 millimeters cross section of the banana. A whole banana is more than 50 ~ 100 times the optimal dose. Any substance eaten in more than 25 times of its optimal dose becomes highly toxic and creates DNA mutations which can cause multiple malignancies in the presence of strong electro-magnetic field. With standard medication given by doctor, patients often become sick and they are unable to reduce body weight, unless medication is reduced or completely stopped. When the amount of zinc is very high, DNA often becomes unstable and multiple cancers can grow rapidly in the presence of strong electromagnetic field. Large amount of Vitamin C from regular orange or orange juice inhibit the most important Vitamin D3 effects. At least 3 kinds of low Vitamin C oranges will not inhibit Vitamin D3. Since B12 particularly methyl cobalamin which is a red small tablet is known to improve brain circulation very significantly we examined its effect within 20 seconds of oral intake we found the following very significant changes. Acetylcholine in both sides of the brain often increases over 4,500 ng. Longevity gene Sirtuin 1 level increases significantly for short time of few hours. Thymosin α1 and Thymosinβ4 both increase to over 1500 ng from 20 ng or less.


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