scholarly journals CRHCeA→VTA inputs inhibit the positive ensembles to induce negative effect of opiate withdrawal

2021 ◽  
Author(s):  
Changyou Jiang ◽  
Xiao Yang ◽  
Guanhong He ◽  
Fan Wang ◽  
Zhilin Wang ◽  
...  
Keyword(s):  
Drug Abuse ◽  
Positive Reinforcement ◽  
Opiate Dependence ◽  
Opiate Withdrawal ◽  
Pathological Changes ◽  
Chronic Morphine ◽  
Neuronal Ensembles ◽  
Negative Effect ◽  
Activity Dependent ◽  
Insight Into

AbstractPlasticity of neurons in the ventral tegmental area (VTA) is critical for establishment of drug dependence. However, the remodeling of the circuits mediating the transition between positive and negative effect remains unclear. Here, we used neuronal activity-dependent labeling technique to characterize and temporarily control the VTA neuronal ensembles recruited by the initial morphine exposure (morphine-positive ensembles, Mor-Ens). Mor-Ens preferentially projected to NAc, and induced dopamine-dependent positive reinforcement. Electrophysiology and rabies viral tracing revealed the preferential connections between the VTA-projective corticotrophin-releasing hormone (CRH) neurons of central amygdala (CRHCeA→VTA) and Mor-Ens, which was enhanced after escalating morphine exposure and mediated the negative effect during opiate withdrawal. Pharmacologic intervention or CRISPR-mediated repression of CRHR1 in Mor-Ens weakened the inhibitory CRHCeA→VTA inputs, and alleviated the negative effect during opiate withdrawal. These data suggest that neurons encoding opioid reward experience are inhibited by enhanced CRHCeA→VTA inputs induced by chronic morphine exposure, leading to negative effect during opiate withdrawal, and provide new insight into the pathological changes in VTA plasticity after drug abuse and mechanism of opiate dependence.

Retracted Confessions: Through Opiate Withdrawal to a New Conceptual Framework

1993 ◽  
Vol 33 (4) ◽  
pp. 285-290 ◽  
Author(s):  
S E Davison ◽  
D M Forshaw
Keyword(s):  
Case Report ◽  
Conceptual Framework ◽  
Drug User ◽  
Opiate Dependence ◽  
Opiate Withdrawal ◽  
Practical Issue ◽  
Current Thinking

We note growing concern by defence councils over the reliability of confessions obtained from suspects withdrawing from opiate dependence. We focus on a case report and highlight the conceptual weaknesses of current thinking about confessions. A philosophical model is adapted to clarify the theoretical aspects and thereby provide a conceptual framework to help the doctor confronted with the practical issue of how to assess a suspect's fitness for interrogation or the reliability of an individual's confession. We argue that the practice of not treating withdrawal in custody is unjust and inhumane. The model presented is of value in dealing with the issues raised by retracted confessions generally and not just in the specific instances where the suspect is a drug user.

scholarly journals Deformation Effect on Water Transport through Nanotubes

Energies ◽  
2019 ◽  
Vol 12 (23) ◽  
pp. 4424 ◽  
Author(s):  
Robinson ◽  
Shahbabaei ◽  
Kim
Keyword(s):  
Molecular Dynamics ◽  
Water Transport ◽  
Boron Nitride Nanotubes ◽  
Fickian Diffusion ◽  
Deformation Effect ◽  
Degree Of Deformation ◽  
Single File ◽  
Negative Effect ◽  
Non Equilibrium Molecular Dynamics ◽  
Insight Into

In this study, we used non-equilibrium molecular dynamics to study the transport of water through deformed (6,6) Carbon Nanotubes (CNTs) and Boron Nitride Nanotubes (BNNTs). The results were then compared with that of the perfect nanotubes. The main aim of this study was to get a better insight into the deformation effect on water transport through nanotubes rather than directly comparing the CNTs and BNNTs. As the diameters of both types of nanotubes differ from each other for the same chiral value, they are not directly comparable. We carried out our study on deformations such as screw distortion, XY-distortion, and Z-distortion. XY-distortion of value 2 shows a change from single-file water transport to near-Fickian diffusion. The XY-distortions of higher value shows a notable negative effect on water transport when their distortion values get larger. These suggest that the degree of deformation plays a crucial role in water transport through deformed nanotubes. The Z-distortion of 2 showed discontinuous single-file chain formation inside the nanotubes. Similar phenomena are observed in both nanotubes, irrespective of their type, while the magnitudes of their effects vary.

Pregnantie Van Context en Effect Ervan op Het Raden, Leren en Onthouden Van Vreemdtalige Woorden

1989 ◽  
Vol 34 ◽  
pp. 32-41
Author(s):  
Jan-Arjen Mondria
Keyword(s):  
Foreign Language ◽  
Negative Correlation ◽  
Classroom Setting ◽  
Word Form ◽  
Sentential Context ◽  
Learning Stage ◽  
Negative Effect ◽  
And Function ◽  
The Relationship ◽  
Insight Into

This paper reports research into the acquisition of vocabulary in a foreign language, more specifically into the supposition that 'guessing' (i.e. inferring the meaning of an unknown word from context and word-form) contributes substantially to retention. Although much is to be said for the latter, the empirical underpinning of this supposition has so far been slight and various questions have remained. In order to gain a better insight into these we have carried out an experiment in a classroom setting, focussing on the following questions: 1.Which factors of context influence the guessability of words? 2.What is the influence of these factors on receptive retention (after guessing and learning)? 3.What is the relationship between guessing and retention? (Are words which have been correctly guessed better retained than words which have not been correctly guessed?) The chief findings of the experiment are: l.A specific ('pregnant') filler of the slots 'subject', 'verb' and 'function' contributes to the guessability of a word in a particular sentential context. 2. A specific ('pregnant') filler of the slots mentioned in guessing and learning has no effect on the retention ('subject' and 'verb') or even a negative effect ('function'). 3.There is no positive correlation between guessing and retention (after guessing and learning; for some words there is even a negative correlation. To sum up: a 'pregnant' context does indeed induce better guessing, but subsequently it does not induce a better retention of the meaning involved, at least not if the guessing stage is followed by a learning stage using the same context as in guessing.

scholarly journals Multiomics Analysis of the mdx/mTR Mouse Model of Duchenne Muscular Dystrophy

2019 ◽  
Author(s):  
Douglas W Van Pelt ◽  
Yalda A Kharaz ◽  
Dylan C Sarver ◽  
Logan R Eckhardt ◽  
Justin T Dzierzawski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Metabolism ◽  
Muscle Disease ◽  
Protein Abundance ◽  
Pathological Changes ◽  
Hindlimb Muscles ◽  
Dystrophin Protein ◽  
Insight Into

AbstractDuchenne muscular dystrophy (DMD) is a progressive neuromuscular disease characterized by extensive muscle weakness. Patients with DMD lack a functional dystrophin protein, which transmits force and organizes the cytoskeleton of skeletal muscle. Multiomic studies evaluate combined changes in the transcriptome, proteome, and metabolome, and have been proposed as a way to obtain novel insight about disease processes from preclinical models. We therefore sought to use this approach to study pathological changes in dystrophic muscles. We evaluated hindlimb muscles of male mdx/mTR mice, which lack a functional dystrophin protein and have deficits in satellite cell abundance and proliferative capacity. Wild type (WT) C57BL/6J mice served as controls. Muscle fiber contractility was measured, along with changes in the transcriptome using RNA sequencing, and in the proteome, metabolome, and lipidome using mass spectroscopy. While mdx/mTR mice displayed gross pathological changes and continued cycles of degeneration and regeneration, we found no differences in fiber contractility between strains. However, there were numerous changes in the transcriptome and proteome related to protein balance, contractile elements, extracellular matrix, and metabolism. There was only a 53% agreement in fold change data between the proteome and transcriptome, highlighting the need to study protein abundance along with gene expression measures. Numerous changes in markers of skeletal muscle metabolism were observed, with dystrophic muscles exhibiting elevated glycolytic metabolites. These findings highlight the utility of multiomics in studying muscle disease, and provide additional insight into the pathological changes in dystrophic muscles that might help to guide evidence-based exercise prescription in DMD patients.

scholarly journals Why not use empirically supported treatments (ESTs)? Attitudes of German and Dutch therapists

2021 ◽  
Author(s):  
Finja Marten ◽  
Leontien de Kwaadsteniet ◽  
Cilia Witteman
Keyword(s):  
Positive Impact ◽  
Group Discussion ◽  
Two Dimensions ◽  
Empirically Supported Treatments ◽  
Online Questionnaire ◽  
Empirically Supported ◽  
Positive Attitudes ◽  
Cognitive Behavioural ◽  
Negative Effect ◽  
Insight Into

We enquired into attitudes towards empirically supported treatments (ESTs), with an online questionnaire completed by 190 German and 400 Dutch therapists. Therapists had different attitudes, ranging from very negative to very positive. Two dimensions could describe these attitudes. A negative one: ESTs are thought to have a negative effect on the process of treatment, and a positive one: ESTs are thought have a positive impact on the outcomes of treatment. We found these dimensions to be related to self-reported use of ESTs. Therapists with a cognitive-behavioural orientation, therapists who were less experienced, and Dutch therapists had more positive attitudes than therapists with other orientations, therapists who were more experienced, or German. In a focus group discussion, Dutch therapists gave further insight into their attitudes and provided several suggestions to improve the use of ESTs.

Influence of material alterations and machine impairment on throughput related sensor-based sorting performance

2020 ◽  
pp. 0734242X2093674
Author(s):  
Bastian Küppers ◽  
Sabine Schlögl ◽  
Karl Friedrich ◽  
Laura Lederle ◽  
Celestine Pichler ◽  
...  
Keyword(s):  
Near Infrared ◽  
Size Distributions ◽  
Particle Size Distributions ◽  
Throughput Rate ◽  
Specific Input ◽  
Infrared Technology ◽  
Negative Effect ◽  
Systematic Effects ◽  
Sensor Based Sorting ◽  
Insight Into

Experiments with sensor-based sorting (SBS) machinery provide insight into the effect of throughput rate and input composition on the sorting performance. For this purpose, material mixtures with certain compositions and particle size distributions were created from waste fractions and sorted at various throughput rates. To evaluate the sorting performance of the SBS unit (using near infrared technology) in dependence of the applied load, four assessment factors concerning the output fractions were studied: yield, product purity, recovery/product quantity and incorrectly discharged share of reject particles. The influences on the assessment parameters of light twodimensional (2D) particles in the input of a sorting stage and failing air valves in an SBS unit were evaluated for various input compositions at different throughput rates. It was found that a share of approximately 5 wt% 2D particles in the input had a similar negative effect on the yield as the malfunction of 20% of all air valves in an SBS machine at high throughput rates. Additionally, the failure of the air valves reduced the product purity of the sorting stage at increased throughput rates. Furthermore, qualitative observations concerning systematic effects of prior studies could be confirmed. Resulting graphs for a specific input composition of an SBS unit at varying throughput rates could be used to adjust the throughput rate to meet the exact demands for a sorting stage.

scholarly journals Local Opiate Withdrawal in Locus Coeruleus Neurons In Vitro

2001 ◽  
Vol 85 (6) ◽  
pp. 2388-2397 ◽  
Author(s):  
Alexander Ivanov ◽  
Gary Aston-Jones
Keyword(s):  
Protein Kinase ◽  
Locus Coeruleus ◽  
Protein Kinase A ◽  
Discharge Rate ◽  
Brain Slices ◽  
Opiate Withdrawal ◽  
Spontaneous Discharge ◽  
Chronic Morphine ◽  
Kinase A

Noradrenergic neurons of the brain nucleus locus coeruleus (LC) become hyperactive during opiate withdrawal. It has been uncertain to what extent such hyperactivity reflects changes in intrinsic properties of these cells. The effects of withdrawal from chronic morphine on the activity of LC neurons were studied using intracellular recordings in rat brain slices. LC neurons in slices from chronically morphine-treated rats exhibited more than twice the frequency of spontaneous action potentials after naloxone compared with LC neurons from control rats. However, after naloxone treatment, the resting membrane potential (MP) of LC neurons from dependent rats was not significantly different from that in control rats. Neither resting MP nor spontaneous discharge rate (SDR) was altered by naloxone in LC neurons from control rats. Neither kynurenic acid nor a cocktail of glutamate and GABA antagonists (6-cyano-7-nitroquinoxalene-2,3-dione + 2-amino-5-phosphonopentanoic acid + bicuculline) blocked the hyperactivity of LC neurons precipitated by naloxone in slices from morphine-dependent rats. The effects of ouabain on MP and SDR were similar in LC neurons from control and morphine-dependent rats. These results indicate that an adaptive change in glutamatergic or GABAergic synaptic mechanisms or altered Na/K pump activity does not underlie the withdrawal-induced activation of LC neurons in vitro. Specific inhibitors of protein kinase A [Rp-cAMPS or N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide (H-89)] partially suppressed the withdrawal hyperactivity of LC neurons, and activators of cAMP (forskolin) or protein kinase A (Sp-cAMPS) increased the discharge rate of LC neurons from control rats. These results suggest that upregulation of cAMP-dependent protein kinase A during chronic morphine treatment is involved in the withdrawal-induced hyperactivity of LC neurons.

scholarly journals 187 Buprenorphine/Naloxone (Suboxone and Bunavail)-Induced Glycolimia, an Indication of Undermedication?

CNS Spectrums ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 107-107 ◽  
Author(s):  
Stefany Kress ◽  
Alan Hirsch
Keyword(s):  
Reward System ◽  
Opiate Dependence ◽  
Opiate Withdrawal ◽  
White Female ◽  
Compensatory Response ◽  
Insulin Dependent ◽  
Typical Day ◽  
High Doses ◽  
Sweet Cravings ◽  
The Brain

AbstractINTRODUCTIONBuprenorphine/Naloxone combination drugs such as Suboxone and Bunavail have not been reported to induce glycolimia. Two such cases are presented.METHODSCASE STUDY: Case 1: A 30-year-old, right-handed, white female with a history of opioid abuse was started on 4.2 mg buprenorphine/0.7 mg naloxone (Bunavail) BID and began sweet cravings and consumption of sweet foods. In a typical day she would eat 16 strawberry pop-tarts and 2 boxes of Little Debbie cookies. This may have provoked the 10 pound weight augmentation in the first two weeks of treatment. She denied any craving for opioids and no evidence of opioid withdrawal was present. Her Clinical Opiate Withdrawal Scale (COWS) score =4 (normal).Case 2: A 51-year-old, right-handed, male with opiate dependence, four days following the initiation of Suboxone (8 mg buprenorphine/2 mg naloxone) BID, developed strong cravings for sugary foods including donuts and ice cream, of which he was previously never inclined to eat and gained 10 pounds in one month. His COWS score= 7 (mild symptoms).DISCUSSIONThere are myriad mechanisms that may be acting to induce sugar cravings with buprenorphine/naloxone. Humans and rats acutely withdrawing from opiates, such as heroin, develop strong urges for consumption of sugary substances (Lieblich et al., 1991; Sapira, 1968; Weiss, 1982). Glycolimia in the above cases may reflect early or subclinical withdrawal, which if becoming more severe, would manifest as opioid craving. If the value of the reward system induced by sweets doesn’t meet the threshold invoked by the opioid stimulation, this “withdrawal” may lead to further sugar cravings in an attempt to reach the same reward level. In animals, certain foods and drugs share the same neurological pathway involved in the “reward system” potentially explaining why opioids influence food palatability in humans (Pelchat, 2002).Alternatively, it is possible that buprenorphine induces hypoglycemia at high doses (Bullingham et al., 1981) such that hypoglycemia may paradoxically act to enhance sugar craving similar to the Somogyi effect in insulin dependent diabetics. Another possible mechanism of action is that since buprenorphine acts to decrease glucose metabolism in the brain (Walsh et al., 1994), this may lead to a neural compensatory response by increasing sugar access to the brain behaviorally via glycolimiaand somatically reducing insulin release, thus explaining the high hemoglobin A1c observed in opioid addicts (Giugliano, 1984). Given the above presentation, complaints of sugar craving may indicate consideration to increase buprenorphine dosing and trial of this in those with glycolimia without opioid dependence may be warranted.Funding AcknowledgementsNo funding.

scholarly journals Pathological Changes in Internal Organs after Blocking Low Hydraulic Resistance Channels along the Stomach Meridian in Pigs

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Wen-Ting Zhou ◽  
Shu-Yong Jia ◽  
Yu-Qing Zhang ◽  
Yu-Ying Tian ◽  
Guang-Jun Wang ◽  
...  
Keyword(s):  
Hydraulic Resistance ◽  
The State ◽  
Pathological Changes ◽  
Internal Organs ◽  
Stomach Meridian ◽  
Normal States ◽  
Low Hydraulic Resistance ◽  
Insight Into ◽  
Experimental Pigs

Objective.The correlation between meridians and organs (Zang-fu) is an important aspect of meridian theory. The objective of this paper is to investigate the pathological changes in the organs resulting from blocking low hydraulic resistance channel (LHRC) along the stomach meridian by injecting gel in pigs so as to offer some insight into the correlation between meridians and internal organs.Methods.Four white piglets and twelve black minipigs were divided into four batches and were observed in different periods. Each batch included two pairs of pigs and each pair matched two pigs with similar conditions among which gel was injected into 6~8 low hydraulic resistance points along the the stomach meridian in the experimental pig and the same amount of saline was injected into the same points in the control pig. The state of stomach and intestine was observed 6~10 weeks after the blocking model was developed.Results.The results showed that there were bloated stomach or/and intestine in all the experimental pigs while there were normal states in seven control pigs except one dead during the experiment.Conclusion.The findings confirmed that the blockage of LHRC along the stomach meridian can influence the state of stomach and intestine, leading to a distension on stomach or/and intestine.

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