Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24.427
Filtrar
1.
Int Arch Occup Environ Health ; 95(3): 559-571, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35220487

RESUMO

OBJECTIVE: Estimate the effort-reward imbalance prevalence (ERI) among physicians. METHODS: A systematic review was conducted from 2005 to 2019 using PRISMA guidelines on the PubMed and EBSCOhost search engines. Data were classified according to the ERI definition used by the authors. A meta-analysis was performed on effort and reward scores and on ERI prevalence rates. RESULTS: Out of 3787 results, we selected 41 studies. The physicians' ERI prevalence rate ranged from 3.50 to 96.9%. The standardized pooled effort mean score was 58.5 for effort and 48.9 for a reward out of 100, respectively. The overall combined ERI rate (when the ratio between effort and reward scores was above 1) was 40.2% among 21,939 practitioners (31.7% in the working European population). ERI rate was 70.2% using a four-point Likert scale and 21.1% using a five-point Likert scale. The highest rate (96.9%) was observed among German rural general practitioners and the lowest rate (3.50%) among Swiss hospital practitioners. The low percentage of variability (I2 = 27%) attributed to effort scores heterogeneity between studies suggested that this dimension is not discriminant in the physician ERI assessment. The high heterogeneity in reward scores (I2 = 83%) indicated that this dimension is sensible in ERI assessment among physicians. The number of items used did not appear as a significant source of heterogeneity. CONCLUSION: Physician job ERI appeared to be higher than in the working population. Studying each dimension and item indicators could help improve psychosocial risk prevention.


Assuntos
Satisfação no Emprego , Médicos , Humanos , Médicos/psicologia , Prevalência , Recompensa , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia , Inquéritos e Questionários , Carga de Trabalho/psicologia
2.
Psychiatr Clin North Am ; 45(3): 321-334, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36055726

RESUMO

While substance experimentation typically begins in adolescence, substance use disorders (SUDs) usually develop in late teens or early adulthood, often in individuals who are vulnerable because of biological and socioeconomic risk factors. Severe SUDs-synonymous with addiction-involve changes in limbic and prefrontal brain areas after chronic drug exposure. These changes involve learned associations between drug reward and cues that trigger the anticipation of that reward (known as incentive salience), as well as heightened dysphoria during withdrawal and weakened prefrontal circuits needed for inhibiting habitual responses.


Assuntos
Comportamento Aditivo , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Adulto , Encéfalo , Humanos , Motivação , Recompensa , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia
3.
Elife ; 112022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-36062909

RESUMO

Adaptive reward-related decision making requires accurate prospective consideration of the specific outcome of each option and its current desirability. These mental simulations are informed by stored memories of the associative relationships that exist within an environment. In this review, I discuss recent investigations of the function of circuitry between the basolateral amygdala (BLA) and lateral (lOFC) and medial (mOFC) orbitofrontal cortex in the learning and use of associative reward memories. I draw conclusions from data collected using sophisticated behavioral approaches to diagnose the content of appetitive memory in combination with modern circuit dissection tools. I propose that, via their direct bidirectional connections, the BLA and OFC collaborate to help us encode detailed, outcome-specific, state-dependent reward memories and to use those memories to enable the predictions and inferences that support adaptive decision making. Whereas lOFC→BLA projections mediate the encoding of outcome-specific reward memories, mOFC→BLA projections regulate the ability to use these memories to inform reward pursuit decisions. BLA projections to lOFC and mOFC both contribute to using reward memories to guide decision making. The BLA→lOFC pathway mediates the ability to represent the identity of a specific predicted reward and the BLA→mOFC pathway facilitates understanding of the value of predicted events. Thus, I outline a neuronal circuit architecture for reward learning and decision making and provide new testable hypotheses as well as implications for both adaptive and maladaptive decision making.


Assuntos
Complexo Nuclear Basolateral da Amígdala , Recompensa , Tonsila do Cerebelo/fisiologia , Complexo Nuclear Basolateral da Amígdala/fisiologia , Tomada de Decisões/fisiologia , Córtex Pré-Frontal/fisiologia , Estudos Prospectivos
4.
BMC Psychiatry ; 22(1): 593, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068526

RESUMO

BACKGROUND: Occupational stress and its health effects on occupational populations have attracted extensive attention from researchers in public health. The stressors faced by employees of power grid enterprises are increasing progressively, which is easy to cause occupational stress. The balance of the body's oxidative-antioxidant levels plays an essential role in maintaining the body's health status. This study aims to explore occupational stress and its correlation with oxidative-antioxidant levels in employees of a power grid enterprise. METHODS: A cluster random sampling method was used to investigate the basic information of 528 employees in a power grid enterprise and investigate the two occupational stress models of employees by using the Job Content Questionnaire based on the job demand-control-support (JDC) model, and the Effort-Reward Imbalance Questionnaire based on the effort-reward imbalance (ERI) model, respectively. Peripheral blood samples were collected from the employees to measure the levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and superoxide dismutase (SOD). The correlation between different models of occupational stress level and the body's oxidation-antioxidation level was further explored. RESULTS: The detection rate of high JDC model occupational stress was 50.6% and the detection rate of high ERI model occupational stress was 50.9%. The JDC model occupational stress was significantly associated with high-temperature and high-altitude operation, visual display terminal operation, monthly income, and exercise (all P < 0.05). The ERI model occupational stress was significantly associated with visual display terminal operation (all P < 0.05). The results of the generalized additive model showed that SOD levels had a non-linear relationship with the D/C ratio as well as the E/R ratio. With the D/C ratio close to 1, SOD levels raised rapidly. When the E/R ratio exceeded 1, the SOD level raised rapidly (all P<0.05) . TAC levels were negatively associated with the E/R ratio (P < 0.05). CONCLUSION: The detection rates of occupational stress in both models among employees in a power grid enterprise are higher. ERI model occupational stress was associated with body TAC and SOD levels, and JDC model occupational stress was associated with body SOD levels.


Assuntos
Antioxidantes , Estresse Ocupacional , Estudos Transversais , Humanos , Satisfação no Emprego , Estresse Oxidativo , Recompensa , Estresse Psicológico , Superóxido Dismutase , Inquéritos e Questionários
5.
Mol Brain ; 15(1): 78, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071471

RESUMO

Our world is full of uncertainty. Animals, including humans, need to behave flexibly to adjust to ever-changing environments. Reversal learning tasks have been used to assess behavioral flexibility in many species. However, there are some limitations in the traditional free-moving methodology, including (1) sessions to train the animals, (2) within-session number of trials associated with reversals, (3) factors of physical movement unrelated to the task in the maze or operant box, and (4) incompatibility with techniques, such as two-photon imaging. Therefore, to address these limitations, we established a novel spatiotemporal Pavlovian head-fixed reversal learning task for mice. Six experimentally naive adult C57BL/6J mice were used in this study. First, we trained head-fixed mice on a fixed-time schedule task. Sucrose solution was delivered every 10 s with a single drinking spout placed within the licking distance of the mice. After the mice showed anticipatory licking toward the timing of sucrose solution delivery, we began training the mice on the fixed-time schedule reversal learning task with two licking spouts. In this task, sucrose solution was delivered through one of the two drinking spouts. The rewarding spout was switched every 10 trials. Mice quickly learned to switch anticipatory licking to the rewarding side of the spouts, suggesting that they learned this head-fixed reversal learning task. Using the head-fixed experimental design, behavioral measures can be simplified by eliminating the complex behavioral sequences observed in free-moving animals. This novel head-fixed reversal learning task is a useful assay for studying the neurobiological mechanism of behavioral flexibility that is impaired in various psychopathological conditions.


Assuntos
Reversão de Aprendizagem , Recompensa , Animais , Comportamento Animal , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Sacarose
6.
Front Public Health ; 10: 953743, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072385

RESUMO

Delay discounting refers to the observation that the subjective value of an outcome decreases as the delay to its receipt increases. It is well-established that steep delay discounting is related to various maladaptive behaviors, including poorer health-related choices. One of the current challenges of public health policies that emerged during the COVID-19 pandemic is to encourage preventive behaviors against infectious diseases. In this study, we aimed to explore possible underpinnings of adherence to COVID-19 related public health policy guidelines such as disinfection, distancing, and masks (DDM). Participants completed monetary and health discounting tasks across two outcome amounts in gain and loss conditions, and they provided self-report measures of adherence to the DDM policy. Contrary to the theoretically plausible prediction that higher discounting rates would be negatively associated with adherence to health-related public policy guidelines, we found no compelling evidence to support such statement. We discuss the potential weaknesses of declarative measurements of attitudes toward COVID-19 and consider using behavioral interventions for influencing discounting rates for complementing and enhancing current policy guidelines.


Assuntos
COVID-19 , Desvalorização pelo Atraso , COVID-19/prevenção & controle , Humanos , Avaliação de Resultados em Cuidados de Saúde , Pandemias , Política Pública , Recompensa
7.
Int J Radiat Oncol Biol Phys ; 114(2): 183, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36055316

Assuntos
Recompensa , Humanos , Risco
8.
Psychiatr Clin North Am ; 45(3): 577-591, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36055740

RESUMO

Modern technology rewards constant engagement and discourages sparing use, opening the door to unhealthy use and even addiction. The technological addictions (TAs) are a newly described set of disorders that come with the technological advances that define the new era. Internet gaming disorder (IGD) is already codified as a proposed diagnosis in the 5th Edition of the Diagnostic and Statistical Manual (DSM-5) of the American Psychiatric Association. Others, such as social media addiction (SMA), are in the earlier stages of our understanding. This article provides an overview of the more common TAs including their evaluation and treatment techniques.


Assuntos
Comportamento Aditivo , Jogos de Vídeo , Comportamento Aditivo/diagnóstico , Comportamento Aditivo/terapia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Internet , Recompensa , Dependência de Tecnologia , Jogos de Vídeo/psicologia
9.
Sci Rep ; 12(1): 15009, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056071

RESUMO

Effort is aversive and often avoided, even when earning benefits for oneself. Yet, people sometimes work hard for others. How do people decide who is worth their effort? Prior work shows people avoid physical effort for strangers relative to themselves, but invest more physical effort for charity. Here, we find that people avoid cognitive effort for others relative to themselves, even when the cause is a personally meaningful charity. In two studies, participants repeatedly decided whether to invest cognitive effort to gain financial rewards for themselves and others. In Study 1, participants (N = 51; 150 choices) were less willing to invest cognitive effort for a charity than themselves. In Study 2, participants (N = 47; 225 choices) were more willing to work cognitively for a charity than an intragroup stranger, but again preferred cognitive exertion that benefited themselves. Computational modeling suggests that, unlike prior physical effort findings, cognitive effort discounted the subjective value of rewards linearly. Exploratory machine learning analyses suggest that people who represented others more similarly to themselves were more willing to invest effort on their behalf, opening up new avenues for future research.


Assuntos
Instituições de Caridade , Recompensa , Cognição , Simulação por Computador , Humanos , Esforço Físico
10.
PLoS One ; 17(9): e0273913, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36048784

RESUMO

Previous studies have suggested positive effects of mindfulness on inhibitory control (stopping behaviour). However, scarce previous studies suggest the relationship may depend on context. We provide first evidence that inhibitory control is challenged when perceiving attractive faces, especially when being mindful. Specifically, we investigated the relationship between mindfulness and inhibitory control and the moderating role of a social reward context (being exposed to attractive opposite sex faces). Participants (n = 50) between 18-43 years old (M = 25, SD = 5.4) filled out questionnaires assessing standard demographic variables and dispositional mindfulness. Subsequently, they performed a Go/No-go task with a neutral condition and attractive faces condition. Results showed that inhibitory control was challenged in the attractive condition relative to the neutral condition, p = 0.019. Dispositional mindfulness was negatively correlated with inhibitory performance, but only in the attractive faces condition (r = -0.32, p = 0.024). Results did not support a moderating role of gender. Finally, though post-hoc, higher mindfulness was associated with reduced perceived attractiveness of presented faces (r = -0.33, p = 0.019). However, the relationship between mindfulness and reduced inhibitory control could not be explained by mindfulness associated reduced attractiveness. Taken together, results show that mindfulness challenges inhibitory control when perceiving attractive faces. This implies that mindfulness interventions aimed at enhancing inhibitory control, may not render the desired effect in a context of being exposed to attractive faces. Though certainly plausible, it remains an open question whether results generalize to other reward contexts as well.


Assuntos
Atenção Plena , Adolescente , Adulto , Animais , Humanos , Atenção Plena/métodos , Personalidade , Recompensa , Animais de Trabalho , Inquéritos e Questionários , Adulto Jovem
11.
Biomed Pharmacother ; 153: 113346, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076473

RESUMO

The I1 imidazoline receptor and its candidate protein imidazoline receptor antisera-selected (IRAS)/Nischarin are linked to µ opioid receptor (MOR) functions associated with MOR trafficking. We previously demonstrated that IRAS may play an important role in the development of morphine tolerance and physical dependence in vivo. However, the effects of IRAS on morphine psychological dependence are not fully understood. To extend these studies, we investigated the impact of IRAS on morphine dependence in conditioned place preference (CPP) experiments and explored the underlying mechanisms. Knockout of IRAS enhanced the acquisition and reinstatement of morphine-induced CPP. Conditional-knockout of IRAS in the nucleus accumbens (NAc) reproduced higher CPP, and overexpression of IRAS in the NAc rescued the increased morphine-induced CPP in IRAS-/- mice. IRAS-/- mice showed dramatic cAMP-dependent protein kinase (PKA) activation, upregulation of the phosphorylation of the AMPA receptor GluR1-S845 and NMDA receptor NR1-S897 in the NAc after CPP experiment. Moreover, knockout of IRAS induced an increase in spontaneous excitatory postsynaptic current (sEPSC) frequency and a decrease in the AMPA/NMDA ratio in the NAc after chronic morphine treatment. The selective AMPA receptor antagonist NBQX could inhibit morphine CPP in WT mice, while its effect was significantly reduced in IRAS-/- mice. Together, our results demonstrate that IRAS contributes to the regulation of morphine dependence and that the alteration of glutamatergic transmission in the NAc may participate in the effect of IRAS.


Assuntos
Dependência de Morfina , Morfina , Animais , Ácido Glutâmico/metabolismo , Receptores de Imidazolinas/metabolismo , Soros Imunes/metabolismo , Soros Imunes/farmacologia , Camundongos , Camundongos Knockout , Morfina/metabolismo , Morfina/farmacologia , Núcleo Accumbens , Receptores de AMPA/metabolismo , Recompensa
12.
Sensors (Basel) ; 22(17)2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36080933

RESUMO

The required navigation performance (RNP) procedure is one of the two basic navigation specifications for the performance-based navigation (PBN) procedure as proposed by the International Civil Aviation Organization (ICAO) through an integration of the global navigation infrastructures to improve the utilization efficiency of airspace and reduce flight delays and the dependence on ground navigation facilities. The approach stage is one of the most important and difficult stages in the whole flying. In this study, we proposed deep reinforcement learning (DRL)-based RNP procedure execution, DRL-RNP. By conducting an RNP approach procedure, the DRL algorithm was implemented, using a fixed-wing aircraft to explore a path of minimum fuel consumption with reward under windy conditions in compliance with the RNP safety specifications. The experimental results have demonstrated that the six degrees of freedom aircraft controlled by the DRL algorithm can successfully complete the RNP procedure whilst meeting the safety specifications for protection areas and obstruction clearance altitude in the whole procedure. In addition, the potential path with minimum fuel consumption can be explored effectively. Hence, the DRL method can be used not only to implement the RNP procedure with a simulated aircraft but also to help the verification and evaluation of the RNP procedure.


Assuntos
Aviação , Aeronaves , Algoritmos , Recompensa
13.
Sensors (Basel) ; 22(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36080961

RESUMO

In an attempt to overcome the limitations of reward-driven representation learning in vision-based reinforcement learning (RL), an unsupervised learning framework referred to as the visual pretraining via contrastive predictive model (VPCPM) is proposed to learn the representations detached from the policy learning. Our method enables the convolutional encoder to perceive the underlying dynamics through a pair of forward and inverse models under the supervision of the contrastive loss, thus resulting in better representations. In experiments with a diverse set of vision control tasks, by initializing the encoders with VPCPM, the performance of state-of-the-art vision-based RL algorithms is significantly boosted, with 44% and 10% improvement for RAD and DrQ at 100 steps, respectively. In comparison to the prior unsupervised methods, the performance of VPCPM matches or outperforms all the baselines. We further demonstrate that the learned representations successfully generalize to the new tasks that share a similar observation and action space.


Assuntos
Algoritmos , Reforço Psicológico , Recompensa
14.
J Int AIDS Soc ; 25(9): e25979, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36109803

RESUMO

INTRODUCTION: To develop a patient-centred financial incentive delivery strategy to improve antiretroviral treatment adherence in adolescents and young adults (AYA) living with HIV in Kisumu, Kenya, we conducted a mixed methods study exploring preferences. METHODS: A discrete choice experiment (DCE) and focus group discussion (FGD) were conducted simultaneously to identify preferences for five incentive delivery strategy features: value, eligibility, recipient, format and disbursement frequency. We used consecutive sampling to recruit AYA (14-24 years) living with HIV attending three health facilities in Kisumu, Kenya. We calculated mean preferences, willingness to trade, latent class membership and predictors of latent class membership. The FGD explored preferred incentive features, and, after deductive and inductive coding, qualitative findings were triangulated with DCE results. RESULTS: Two hundred and seven AYA living with HIV (46% 14-17 years, 54% 18-24 years; 33% male sex, 89% viral load <50 copies/ml) were recruited to the study (28 October-16 November 2020). Two distinct preference phenotypes emerged from the DCE analysis (N = 199), 44.8% of the population fell into an "immediate reward" group, who wanted higher value cash or mobile money distributed at each clinic visit, and 55.2% fell into a "moderate spender" group, who were willing to accept lower value incentives in the form of cash or shopping vouchers, and accrued payments. The immediate reward group were willing to trade up to 200 Kenyan Shillings (KSH)-approximately 2 US dollars (USD)-of their 500 KSH (∼5 USD) incentive to get monthly as opposed to accrued yearly payments. The strongest predictor of latent class membership was age (RR 1.45; 95% CI: 1.08-1.95; p = 0.006). Qualitative data highlighted the unique needs of those attending boarding school and confirmed an overwhelming preference for cash incentives which appeared to provide the greatest versatility for use. CONCLUSIONS: Providing small financial incentives as cash was well-aligned with AYA preferences in this setting. AYA should additionally be offered a choice of other incentive delivery features (such as mobile money, recipient and disbursement frequency) to optimally align with the specific needs of their age group and life stage.


Assuntos
Infecções por HIV , Motivação , Feminino , Grupos Focais , Infecções por HIV/tratamento farmacológico , Humanos , Quênia , Masculino , Recompensa
15.
J Environ Public Health ; 2022: 3919519, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36111067

RESUMO

Teenage depression, also known as TD, is a common mental illness that is characterized by symptoms such as hopelessness, helplessness, pessimism, depression, and decreased energy. It has always been a hot topic to discuss how rewards and punishments work in education. In order to prevent and treat adolescent depression, this study examines the mechanisms of educational reinforcement and punishment as well as psychological interventions. In this study, the activated brain regions are analyzed using data mining (DM) technology to determine whether they are significantly more or less active than the rest of the brain of students who are not experiencing negative emotions. When the word vector has 90 dimensions, the results demonstrate that the average F1 value of the weighted word vector method is 81.3 percent. It has been established that the approach taken in this work offers a reliable way to diagnose TD.


Assuntos
Intervenção Psicossocial , Punição , Adolescente , Depressão/psicologia , Humanos , Punição/psicologia , Recompensa , Estudantes
16.
PLoS One ; 17(9): e0274272, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36094920

RESUMO

When comparing the performance of multi-armed bandit algorithms, the potential impact of missing data is often overlooked. In practice, it also affects their implementation where the simplest approach to overcome this is to continue to sample according to the original bandit algorithm, ignoring missing outcomes. We investigate the impact on performance of this approach to deal with missing data for several bandit algorithms through an extensive simulation study assuming the rewards are missing at random. We focus on two-armed bandit algorithms with binary outcomes in the context of patient allocation for clinical trials with relatively small sample sizes. However, our results apply to other applications of bandit algorithms where missing data is expected to occur. We assess the resulting operating characteristics, including the expected reward. Different probabilities of missingness in both arms are considered. The key finding of our work is that when using the simplest strategy of ignoring missing data, the impact on the expected performance of multi-armed bandit strategies varies according to the way these strategies balance the exploration-exploitation trade-off. Algorithms that are geared towards exploration continue to assign samples to the arm with more missing responses (which being perceived as the arm with less observed information is deemed more appealing by the algorithm than it would otherwise be). In contrast, algorithms that are geared towards exploitation would rapidly assign a high value to samples from the arms with a current high mean irrespective of the level observations per arm. Furthermore, for algorithms focusing more on exploration, we illustrate that the problem of missing responses can be alleviated using a simple mean imputation approach.


Assuntos
Algoritmos , Simulação por Computador , Humanos , Pesquisa , Recompensa
17.
Cell ; 185(19): 3568-3587.e27, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36113428

RESUMO

Computational analysis of cellular activity has developed largely independently of modern transcriptomic cell typology, but integrating these approaches may be essential for full insight into cellular-level mechanisms underlying brain function and dysfunction. Applying this approach to the habenula (a structure with diverse, intermingled molecular, anatomical, and computational features), we identified encoding of reward-predictive cues and reward outcomes in distinct genetically defined neural populations, including TH+ cells and Tac1+ cells. Data from genetically targeted recordings were used to train an optimized nonlinear dynamical systems model and revealed activity dynamics consistent with a line attractor. High-density, cell-type-specific electrophysiological recordings and optogenetic perturbation provided supporting evidence for this model. Reverse-engineering predicted how Tac1+ cells might integrate reward history, which was complemented by in vivo experimentation. This integrated approach describes a process by which data-driven computational models of population activity can generate and frame actionable hypotheses for cell-type-specific investigation in biological systems.


Assuntos
Habenula , Recompensa , Dinâmica Populacional
18.
Psychopharmacology (Berl) ; 239(10): 3313-3323, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36094619

RESUMO

The pathophysiology of schizophrenia involves abnormal reward processing, thought to be due to disrupted striatal and dopaminergic function. Consistent with this hypothesis, functional magnetic resonance imaging (fMRI) studies using the monetary incentive delay (MID) task report hypoactivation in the striatum during reward anticipation in schizophrenia. Dopamine neuron activity is modulated by striatal GABAergic interneurons. GABAergic interneuron firing rates, in turn, are related to conductances in voltage-gated potassium 3.1 (Kv3.1) and 3.2 (Kv3.2) channels, suggesting that targeting Kv3.1/3.2 could augment striatal function during reward processing. Here, we studied the effect of a novel potassium Kv3.1/3.2 channel modulator, AUT00206, on striatal activation in patients with schizophrenia, using the MID task. Each participant completed the MID during fMRI scanning on two occasions: once at baseline, and again following either 4 weeks of AUT00206 or placebo treatment. We found a significant inverse relationship at baseline between symptom severity and reward anticipation-related neural activation in the right associative striatum (r = -0.461, p = 0.035). Following treatment with AUT00206, there was a significant increase in reward anticipation-related activation in the left associative striatum (t(13) = 4.23, peak-level p(FWE) < 0.05)), but no significant effect in the ventral striatum. This provides preliminary evidence that the Kv3.1/3.2 potassium channel modulator, AUT00206, may address reward-related striatal abnormalities in schizophrenia.


Assuntos
Esquizofrenia , Estriado Ventral , Humanos , Imageamento por Ressonância Magnética , Recompensa , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Canais de Potássio Shaw , Estriado Ventral/fisiologia
19.
Cell Rep ; 40(10): 111309, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36070693

RESUMO

Dysfunctional dopamine signaling is implicated in various neuropsychological disorders. Previously, we reported that dopamine increases D1 receptor (D1R)-expressing medium spiny neuron (MSN) excitability and firing rates in the nucleus accumbens (NAc) via the PKA/Rap1/ERK pathway to promote reward behavior. Here, the results show that the D1R agonist, SKF81297, inhibits KCNQ-mediated currents and increases D1R-MSN firing rates in murine NAc slices, which is abolished by ERK inhibition. In vitro ERK phosphorylates KCNQ2 at Ser414 and Ser476; in vivo, KCNQ2 is phosphorylated downstream of dopamine signaling in NAc slices. Conditional deletion of Kcnq2 in D1R-MSNs reduces the inhibitory effect of SKF81297 on KCNQ channel activity, while enhancing neuronal excitability and cocaine-induced reward behavior. These effects are restored by wild-type, but not phospho-deficient KCNQ2. Hence, D1R-ERK signaling controls MSN excitability via KCNQ2 phosphorylation to regulate reward behavior, making KCNQ2 a potential therapeutical target for psychiatric diseases with a dysfunctional reward circuit.


Assuntos
Dopamina , Canal de Potássio KCNQ2 , Transtornos Mentais , Proteínas do Tecido Nervoso , Animais , Dopamina/metabolismo , Canal de Potássio KCNQ2/metabolismo , Transtornos Mentais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Fosforilação , Receptores de Dopamina D1/metabolismo , Recompensa
20.
Biol Res ; 55(1): 28, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088447

RESUMO

Atopic dermatitis (AD) is highly comorbid with negative emotions such as anxiety and depression. Although acupuncture has demonstrated efficacy in AD, its influence on comorbid anxiety and depression remains unclear. We sought to explore the impact and mechanisms of action of acupuncture on comorbid anxiety and depression of AD. AD-like skin lesions were induced by the topical application of MC903 to the mouse cheek. Acupuncture was performed at Gok-Ji (LI11) acupoints. AD-like phenotypes were quantified by lesion scores, scratching behavior, and histopathological changes. The effects of acupuncture on comorbid anxiety and depression-like behaviors were assessed using the elevated plus-maze (EPM), open-field tests (OFT), and tail-suspension test (TST). In addition, biochemical changes in the brain reward regions were investigated by immunoblotting for the expression of tyrosine hydroxylase (TH), dopamine D1 receptor (D1R), phospho-dopamine and cAMP-regulated phosphoprotein-32 kDa (pDARPP-32), phospho-cAMP response element binding protein (pCREB), ΔFosB, and brain-derived neurotrophic factor (BDNF) in the nucleus accumbens, dorsolateral striatum, and ventral tegmental area. Acupuncture effectively improved the chronic itching and robust AD-like skin lesions with epidermal thickening. Additionally, it considerably reduced comorbid anxiety- and depression-like symptoms, as indicated by more time spent in the open arms of the EPM and in the center of the open field and less time spent immobile in the TST. Higher pCREB, ΔFosB, BDNF, and pDARPP-32 levels, and reduced TH and D1R protein expression in the brain reward regions of AD mice were reversed by acupuncture treatment. The beneficial effects of acupuncture on clinical symptoms (scratching behavior) and comorbid psychological distress in AD strongly correlated with dorsal striatal ΔFosB levels. Collectively, these data indicate that acupuncture had a significant, positive impact on comorbid anxiety- and depression-like behaviors by modulating neuroadaptation in the brain reward circuit in mice with AD, providing a novel perspective for the non-pharmacological management of psychiatric comorbidities of AD.


Assuntos
Terapia por Acupuntura , Dermatite Atópica , Animais , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Encéfalo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Dermatite Atópica/complicações , Dermatite Atópica/psicologia , Dermatite Atópica/terapia , Modelos Animais de Doenças , Camundongos , Recompensa
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...