RESUMO
Model-free and model-based computations are argued to distinctly update action values that guide decision-making processes. It is not known, however, if these model-free and model-based reinforcement learning mechanisms recruited in operationally based instrumental tasks parallel those engaged by pavlovian-based behavioral procedures. Recently, computational work has suggested that individual differences in the attribution of incentive salience to reward predictive cues, that is, sign- and goal-tracking behaviors, are also governed by variations in model-free and model-based value representations that guide behavior. Moreover, it is not appreciated if these systems that are characterized computationally using model-free and model-based algorithms are conserved across tasks for individual animals. In the current study, we used a within-subject design to assess sign-tracking and goal-tracking behaviors using a pavlovian conditioned approach task and then characterized behavior using an instrumental multistage decision-making (MSDM) task in male rats. We hypothesized that both pavlovian and instrumental learning processes may be driven by common reinforcement-learning mechanisms. Our data confirm that sign-tracking behavior was associated with greater reward-mediated, model-free reinforcement learning and that it was also linked to model-free reinforcement learning in the MSDM task. Computational analyses revealed that pavlovian model-free updating was correlated with model-free reinforcement learning in the MSDM task. These data provide key insights into the computational mechanisms mediating associative learning that could have important implications for normal and abnormal states.SIGNIFICANCE STATEMENT Model-free and model-based computations that guide instrumental decision-making processes may also be recruited in pavlovian-based behavioral procedures. Here, we used a within-subject design to test the hypothesis that both pavlovian and instrumental learning processes were driven by common reinforcement-learning mechanisms. Sign-tracking and goal-tracking behaviors were assessed in rats using a pavlovian conditioned approach task, and then instrumental behavior was characterized using an MSDM task. We report that sign-tracking behavior was associated with greater model-free, but not model-based, learning in the MSDM task. These data suggest that pavlovian and instrumental behaviors may be driven by conserved reinforcement-learning mechanisms.
Assuntos
Reforço Psicológico , Recompensa , Ratos , Masculino , Animais , Aprendizagem , Motivação , Condicionamento Operante , Sinais (Psicologia)RESUMO
BACKGROUND: Japanese knotweed (Reynoutria japonica var. japonica), a problematic invasive species, has a wide geographical distribution. We have previously shown the potential for attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy and chemometrics to segregate regional differentiation between Japanese knotweed plants. However, the contribution of environment to spectral differences remains unclear. Herein, the response of Japanese knotweed to varied environmental habitats has been studied. Eight unique growth environments were created by manipulation of the red: far-red light ratio (R: FR), water availability, nitrogen, and micronutrients. Their impacts on plant growth, photosynthetic parameters, and ATR-FTIR spectral profiles, were explored using chemometric techniques, including principal component analysis (PCA), linear discriminant analysis, support vector machines (SVM) and partial least squares regression. Key wavenumbers responsible for spectral differences were identified with PCA loadings, and molecular biomarkers were assigned. Partial least squared regression (PLSR) of spectral absorbance and root water potential (RWP) data was used to create a predictive model for RWP. RESULTS: Spectra from plants grown in different environments were differentiated using ATR-FTIR spectroscopy coupled with SVM. Biomarkers highlighted through PCA loadings corresponded to several molecules, most commonly cell wall carbohydrates, suggesting that these wavenumbers could be consistent indicators of plant stress across species. R: FR most affected the ATR-FTIR spectra of intact dried leaf material. PLSR prediction of root water potential achieved an R2 of 0.8, supporting the potential use of ATR-FTIR spectrometers as sensors for prediction of plant physiological parameters. CONCLUSIONS: Japanese knotweed exhibits environmentally induced phenotypes, indicated by measurable differences in their ATR-FTIR spectra. This high environmental plasticity reflected by key biomolecular changes may contribute to its success as an invasive species. Light quality (R: FR) appears critical in defining the growth and spectral response to environment. Cross-species conservation of biomarkers suggest that they could function as indicators of plant-environment interactions including abiotic stress responses and plant health.
Assuntos
Fenótipo , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Análise de Componente Principal , Espécies Introduzidas , Folhas de Planta/química , FotossínteseRESUMO
Plant hormones are important in the control of physiological and developmental processes including seed germination, senescence, flowering, stomatal aperture, and ultimately the overall growth and yield of plants. Many currently available methods to quantify such growth regulators quickly and accurately require extensive sample purification using complex analytic techniques. Herein we used ultra-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) to create and validate the prediction of hormone concentrations made using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectral profiles of both freeze-dried ground leaf tissue and extracted xylem sap of Japanese knotweed (Reynoutria japonica) plants grown under different environmental conditions. In addition to these predictions made with partial least squares regression, further analysis of spectral data was performed using chemometric techniques, including principal component analysis, linear discriminant analysis, and support vector machines (SVM). Plants grown in different environments had sufficiently different biochemical profiles, including plant hormonal compounds, to allow successful differentiation by ATR-FTIR spectroscopy coupled with SVM. ATR-FTIR spectral biomarkers highlighted a range of biomolecules responsible for the differing spectral signatures between growth environments, such as triacylglycerol, proteins and amino acids, tannins, pectin, polysaccharides such as starch and cellulose, DNA and RNA. Using partial least squares regression, we show the potential for accurate prediction of plant hormone concentrations from ATR-FTIR spectral profiles, calibrated with hormonal data quantified by UHPLC-HRMS. The application of ATR-FTIR spectroscopy and chemometrics offers accurate prediction of hormone concentrations in plant samples, with advantages over existing approaches.
Assuntos
Reguladores de Crescimento de Plantas , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Reguladores de Crescimento de Plantas/análise , Análise dos Mínimos Quadrados , Folhas de Planta/química , Cromatografia Líquida de Alta Pressão/métodos , Máquina de Vetores de Suporte , Espectrometria de Massas/métodos , Análise de Componente PrincipalRESUMO
N-methyl-D-aspartate receptor (NMDAR) modulators have recently received increased attention as potential therapeutics for posttraumatic stress disorder (PTSD). Here, we tested a novel NMDAR-positive modulator, NYX-783, in the following two rodent models of PTSD: an auditory fear-conditioning model and a single-prolonged stress (SPS) model. We examined the ability of NYX-783 to reduce subsequent fear-based behaviors by measuring enhanced fear extinction and reduced spontaneous recovery (spontaneous return of fear) in male mice. NYX-783 administration significantly reduced spontaneous recovery in both PTSD models and enhanced fear extinction in the SPS model. Furthermore, NYX-783 increased the NMDA-induced inward currents of excitatory and inhibitory neurons in the infralimbic medial prefrontal cortex (IL mPFC) and that the GluN2B subunit of NMDARs on pyramidal neurons in the IL mPFC is required for its effect on spontaneous recovery. The downstream expression of brain-derived neurotrophic factor was required for NYX-783 to achieve its behavioral effect. These results elucidate the cellular targets of NYX-783 and the molecular mechanisms underlying the inhibition of spontaneous recovery. These preclinical findings support the hypothesis that NYX-783 may have therapeutic potential for PTSD treatment and may be particularly useful for inhibiting spontaneous recovery.
Assuntos
Medo , Receptores de N-Metil-D-Aspartato , Animais , Extinção Psicológica/fisiologia , Medo/fisiologia , Masculino , Camundongos , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
INTRODUCTION: Implementation of interprofessional education (IPE) is recognised as challenging, and well-designed programs can have differing levels of success depending on implementation quality. The aim of this review was to summarise the evidence for implementation of IPE, and identify challenges and key lessons to guide faculty in IPE implementation. METHODS: Five stage scoping review of methodological characteristics, implementation components, challenges and key lessons in primary studies in IPE. Thematic analysis using a framework of micro (teaching), meso (institutional), and macro (systemic) level education factors was used to synthesise challenges and key lessons. RESULTS: Twenty-seven primary studies were included in this review. Studies were predominantly descriptive in design and implementation components inconsistently reported. IPE was mostly integrated into curricula, optional, involved group learning, and used combinations of interactive and didactic approaches. Micro level implementation factors (socialisation issues, learning context, and faculty development), meso level implementation factors (leadership and resources, administrative processes), and macro level implementation factors (education system, government policies, social and cultural values) were extrapolated. Sustainability was identified as an additional factor in IPE implementation. CONCLUSION: Lack of complete detailed reporting limits evidence of IPE implementation, however, this review highlighted challenges and yielded key lessons to guide faculty in the implementation of IPE.
Assuntos
Currículo , Educação Interprofissional , Humanos , Escolaridade , Docentes , LiderançaRESUMO
OBJECTIVES: Antidepressants, specifically Selective Serotonin Re-uptake Inhibitors (SSRIs), that alter serotonin metabolism are currently the most commonly prescribed drugs for the treatment of depression. There is some evidence to suggest these drugs contribute to birth defects. As jaw development is often altered in craniofacial birth defects, the purpose of this study was to interrogate the effects of in utero SSRI exposure in a preclinical model of mandible development. MATERIALS AND METHODS: Wild-type C57BL6 mice were used to produce litters that were exposed in utero to an SSRI, Citalopram (500 µg/day). Murine mandibles from P15 pups were analysed for a change in shape and composition. RESULTS: Analysis indicated an overall shape change with total mandibular length and ramus height being shorter in exposed pups as compared to controls. Histomorphometric analysis revealed that first molar length was longer in exposed pups while third molar length was shorter in exposed as compared to control. Histological investigation of molars and surrounding periodontium revealed no change in collagen content of the molar in exposed pups, some alteration in collagen composition in the periodontium, increased alkaline phosphatase in molars and periodontium and decreased mesenchymal cell marker presence in exposed mandibles. CONCLUSION: The results of this study reveal SSRI exposure may interrupt mandible growth as well as overall dental maturation in a model of development giving insight into the expectation that children exposed to SSRIs may require orthodontic intervention.
Assuntos
Inibidores Seletivos de Recaptação de Serotonina , Serotonina , Animais , Camundongos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Serotonina/metabolismo , Camundongos Endogâmicos C57BL , Citalopram/efeitos adversos , Mandíbula/metabolismoRESUMO
Emerging data indicate that endocannabinoid signaling is critical to the formation of habitual behavior. Previous work demonstrated that antagonism of cannabinoid receptor type 1 (CB1R) with AM251 during operant training impairs habit formation, but it is not known if this behavioral effect is specific to disrupted signaling of the endocannabinoid ligands anandamide or 2-arachidonoyl glycerol (2-AG). Here, we used selective pharmacological compounds during operant training to determine the impact of fatty acid amide hydrolase (FAAH) inhibition to increase anandamide (and other n-acylethanolamines) or monoacylglycerol lipase (MAGL) inhibition to increase 2-AG levels on the formation of habitual behaviors in mice using a food-reinforced contingency degradation procedure. We found, contrary to our hypothesis, that inhibition of FAAH and of MAGL disrupted the formation of habits. Next, AM251 was administered during training to verify that impaired habit formation could be assessed using contingency degradation. AM251-exposed mice responded at lower rates during training and at higher rates in the test. To understand the inconsistency with published data, we performed a proof-of-principle dose-response experiment to compare AM251 in our vehicle-solution to the published vehicle-suspension on response rates. We found consistent reductions in response rate with increasing doses of AM251 in solution and an inconsistent dose-response relationship with AM251 in suspension. Together, our data suggest that further characterization of the role of CB1R signaling in the formation of habitual responding is warranted and that augmenting endocannabinoids may have clinical utility for prophylactically preventing aberrant habit formation such as that hypothesized to occur in substance use disorders.
Assuntos
Endocanabinoides , Monoacilglicerol Lipases , Amidoidrolases/metabolismo , Animais , Endocanabinoides/metabolismo , Endocanabinoides/farmacologia , Inibidores Enzimáticos/farmacologia , Hábitos , Camundongos , Monoacilglicerol Lipases/metabolismo , Receptor CB1 de CanabinoideRESUMO
ISSUE ADDRESSED: The Red Lotus Critical Health Promotion Model (RLCHPM) is designed to support critical health promotion practice. This study investigated the impact of the use of the RLCHPM as a pedagogical framework for competency-based university curricula on the practice of graduates from health promotion programs from an Australian regional university. METHODS: A mixed methods study was undertaken, including an online survey of all 195 graduates from 2008 to 2016, followed by semi-structured interviews with a subset of respondents. RESULTS: There were 95 survey respondents and 10 interviewees. More than half of the survey respondents reported that the model impacted health promotion programs they are involved in, however, less than a quarter felt it impacted workplace policies. The impact was significantly higher for those with higher levels of knowledge about, confidence in using, and perception of utility of the RLCHPM, and stronger alignment of their practice with critical health promotion values and principles. Graduates' embodiment of the model's values and principles in practice enhanced the impact of the model. Factors that limited the impact included participants' implicit use of components of the model without explicit reference to the model, and the incongruence between participants' professional practice ideals and those of their workplace context. CONCLUSIONS: The use of the RLCHPM as a pedagogical framework for university health promotion programs positively impacted graduates' practice within the Australian context. SO WHAT?: The RLCHPM could be used as a pedagogical framework in universities to develop competency-based critical health promotion curricula to enable graduates to progress critical health promotion practice.
Assuntos
Promoção da Saúde , Prática Profissional , Humanos , Austrália , CurrículoRESUMO
ISSUE ADDRESSED: Ethical values underpin the health promotion discipline and profession, and competencies required for professional practice. Understanding how ethical values are translated into professional practice is critical. The aim of this exploratory sequential mixed methods study was to explore Australian health promotion stakeholder perspectives about ethical health promotion practice. METHODS: A face-to-face group-based workshop (n = 15), online survey (n = 77) and in-depth individual interviews (n = 15) collected qualitative and quantitative data from health promotion stakeholders. Descriptive statistics were used to analyse quantitative and thematic analysis to analyse qualitative data. RESULTS: Tensions emerged regarding the nomenclature of ethical health promotion practice, with ethics framed largely by participants as related to formal approval for research. A range of barriers and enablers to ethical practice were identified. Barriers related to obtaining ethical approvals and working with specific population groups and communities. Enablers included professional development opportunities, access to a specialised human research ethics committee and a better understanding of what is meant by 'ethical practice'. CONCLUSION: Findings suggest the need for an ethical health promotion practice framework and resources for practitioners and organisations throughout Australia. We propose a framework comprising two pillars: (a) developing critical practice; and (b) building the evidence-based for health promotion. SO WHAT?: This study recognises the need for increased dialogue about the ethical foundations of health promotion. The development of a health promotion ethics framework can better support the development of ethical practice in the Australian health promotion discipline and profession.
Assuntos
Promoção da Saúde , Austrália , HumanosRESUMO
The most dynamic period of postnatal brain development occurs during adolescence, the period between childhood and adulthood. Neuroimaging studies have observed morphologic and functional changes during adolescence, and it is believed that these changes serve to improve the functions of circuits that underlie decision-making. Direct evidence in support of this hypothesis, however, has been limited because most preclinical decision-making paradigms are not readily translated to humans. Here, we developed a reversal-learning protocol for the rapid assessment of adaptive choice behavior in dynamic environments in rats as young as postnatal day 30. A computational framework was used to elucidate the reinforcement-learning mechanisms that change in adolescence and into adulthood. Using a cross-sectional and longitudinal design, we provide the first evidence that value-based choice behavior in a reversal-learning task improves during adolescence in male and female Long-Evans rats and demonstrate that the increase in reversal performance is due to alterations in value updating for positive outcomes. Furthermore, we report that reversal-learning trajectories in adolescence reliably predicted reversal performance in adulthood. This novel behavioral protocol provides a unique platform for conducting biological and systems-level analyses of the neurodevelopmental mechanisms of decision-making.SIGNIFICANCE STATEMENT The neurodevelopmental adaptations that occur during adolescence are hypothesized to underlie age-related improvements in decision-making, but evidence to support this hypothesis has been limited. Here, we describe a novel behavioral protocol for rapidly assessing adaptive choice behavior in adolescent rats with a reversal-learning paradigm. Using a computational approach, we demonstrate that age-related changes in reversal-learning performance in male and female Long-Evans rats are linked to specific reinforcement-learning mechanisms and are predictive of reversal-learning performance in adulthood. Our behavioral protocol provides a unique platform for elucidating key components of adolescent brain function.
Assuntos
Condicionamento Operante/fisiologia , Reforço Psicológico , Reversão de Aprendizagem/fisiologia , Fatores Etários , Animais , Feminino , Humanos , Masculino , Ratos , Ratos Long-EvansRESUMO
Decades of research have shown that the NAc is a critical region influencing addiction, mood, and food consumption through its effects on reinforcement learning, motivation, and hedonic experience. Pharmacological studies have demonstrated that inhibition of the NAc shell induces voracious feeding, leading to the hypothesis that the inhibitory projections that emerge from the NAc normally act to restrict feeding. While much of this work has focused on projections to the lateral hypothalamus, the role of NAc projections to the VTA in the control food intake has been largely unexplored. Using a retrograde viral labeling technique and real-time monitoring of neural activity with fiber photometry, we find that medial NAc shell projections to the VTA (mNAcâVTA) are inhibited during food-seeking and food consumption in male mice. We also demonstrate that this circuit bidirectionally controls feeding: optogenetic activation of NAc projections to the VTA inhibits food-seeking and food intake (in both sexes), while optogenetic inhibition of this circuit potentiates food-seeking behavior. Additionally, we show that activity of the NAc to VTA pathway is necessary for adaptive inhibition of food intake in response to external cues. These data provide new insight into NAc control over feeding in mice, and contribute to an emerging literature elucidating the role of inhibitory midbrain feedback within the mesolimbic circuit.SIGNIFICANCE STATEMENT The medial NAc has long been known to control consummatory behavior, with particular focus on accumbens projections to the lateral hypothalamus. Conversely, NAc projections to the VTA have mainly been studied in the context of drug reward. We show that NAc projections to the VTA bidirectionally control food intake, consistent with a permissive role in feeding. Additionally, we show that this circuit is normally inactivated during consumption and food-seeking. Together, these findings elucidate how mesolimbic circuits control food consumption.
Assuntos
Comportamento Consumatório/fisiologia , Ingestão de Alimentos/fisiologia , Núcleo Accumbens/fisiologia , Área Tegmentar Ventral/fisiologia , Animais , Condicionamento Operante/fisiologia , Masculino , Camundongos , Atividade Motora/fisiologia , Vias Neurais/fisiologia , Optogenética , RecompensaRESUMO
BACKGROUND: Japanese knotweed (R. japonica var japonica) is one of the world's 100 worst invasive species, causing crop losses, damage to infrastructure, and erosion of ecosystem services. In the UK, this species is an all-female clone, which spreads by vegetative reproduction. Despite this genetic continuity, Japanese knotweed can colonise a wide variety of environmental habitats. However, little is known about the phenotypic plasticity responsible for the ability of Japanese knotweed to invade and thrive in such diverse habitats. We have used attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy, in which the spectral fingerprint generated allows subtle differences in composition to be clearly visualized, to examine regional differences in clonal Japanese knotweed. RESULTS: We have shown distinct differences in the spectral fingerprint region (1800-900 cm- 1) of Japanese knotweed from three different regions in the UK that were sufficient to successfully identify plants from different geographical regions with high accuracy using support vector machine (SVM) chemometrics. CONCLUSIONS: These differences were not correlated with environmental variations between regions, raising the possibility that epigenetic modifications may contribute to the phenotypic plasticity responsible for the ability of R. japonica to invade and thrive in such diverse habitats.
Assuntos
Fallopia japonica/crescimento & desenvolvimento , Espectroscopia de Infravermelho com Transformada de Fourier , Adaptação Fisiológica/genética , Clima , Meio Ambiente , Fallopia japonica/química , Fallopia japonica/genética , Espécies Introduzidas , Filogeografia , SoloRESUMO
BACKGROUND: Outcome of infants with tracheostomy have not been well described in the literature. Our objective was to describe the respiratory, growth, and survival outcomes of infants with tracheostomy. METHODS: A retrospective study was conducted on 204 infants born between 2005 and 2015 with tracheostomy at <1 year of age and follow-up in the Infant Tracheostomy and Home Ventilator Clinic up to 4 years of age. RESULTS: The mean age at tracheostomy was 4.5 months with median age of 3 months. Median age of decannulation was 32 months. The time from tracheostomy placement to complete discontinuation of mechanical ventilation was 15.4 months and from tracheostomy to decannulation was 33.8 months. Mortality rate was 21% and median age of death was 18 months. Preterm infants with acquired airway and lung disease (BPD) and born at <28 weeks' gestation had a significantly higher survival rate compared to term infants. The z-scores for weight and weight for length improved from the time of discharge (mean chronological age 6.5 months) to first year and remained consistent through 3 years. CONCLUSIONS: Premature infants had a higher rate of discontinuation of mechanical ventilation and decannulation compared to term infants. These infants showed consistent growth and comparable survival rate. IMPACT: Infants with tracheostomy and ventilator dependence followed in a multidisciplinary clinic model may have improved survival, growth, and earlier time to decannulation. Preterm infants with acquired airway and lung disease (BPD) with tracheostomy had a higher survival rate compared to term infants with various tracheostomy indications. The age at tracheostomy in infants was 4.5 months and of decannulation was 37 months. Time from tracheostomy to complete discontinuation of mechanical ventilation was 15.4 months. Addition of this data to the sparse literature will be crucial in counseling the families and education of medical staff.
Assuntos
Desenvolvimento Infantil , Pneumopatias/terapia , Pulmão/fisiopatologia , Respiração Artificial , Traqueostomia , Fatores Etários , Pré-Escolar , Feminino , Idade Gestacional , Humanos , Lactente , Lactente Extremamente Prematuro , Pneumopatias/diagnóstico , Pneumopatias/mortalidade , Pneumopatias/fisiopatologia , Masculino , Recuperação de Função Fisiológica , Respiração Artificial/efeitos adversos , Respiração Artificial/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Traqueostomia/efeitos adversos , Traqueostomia/mortalidade , Resultado do Tratamento , Aumento de PesoRESUMO
BACKGROUND: Metabotropic glutamate receptor 5 (mGlu5) plays an important role in excessive alcohol use and the mGlu5/Homer2/Erk2 signaling pathway has been implicated in binge drinking. The mGlu5 negative allosteric modulator (NAM) 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) has been shown to reduce binge drinking in male mice, but less is known about its effect on female mice. Here, we sought to determine whether sex differences exists in the effects of MPEP on binge drinking and whether they relate to changes in the MPEP mGlu5/Homer2/Erk2 signaling. METHODS: We measured the dose-response effect of MPEP on alcohol consumption in male and female mice using the Drinking in the Dark (DID) paradigm to assess potential sex differences. To rule out possible confounds of MPEP on locomotion, we measured the effects of MPEP on locomotor activity and drinking simultaneously during DID. Lastly, to test whether MPEP-induced changes in alcohol consumption were related to changes in Homer2 or Erk2 expression, we performed qPCR using brain tissue acquired from mice that had undergone 7 days of DID. RESULTS: 30 mg/kg MPEP reduced binge alcohol consumption across female and male mice, with no sex differences in the dose-response relationship. Locomotor activity did not mediate the effects of MPEP on alcohol intake, but activity correlated with alcohol intake independent of MPEP. MPEP did not change the expression of Homer2 and Erk2 mRNA in the bed nucleus of the stria terminalis (BNST) or nucleus accumbens in mice whose drinking was reduced by MPEP, relative to saline. There was a positive relationship between alcohol intake and Homer2 expression in the BNST. CONCLUSIONS: MPEP reduced alcohol consumption during DID in male and female C57BL/6 mice but did not change Homer2/Erk2 expression. Locomotor activity did not mediate the effects of MPEP on alcohol intake, though it correlated with alcohol intake. Alcohol intake during DID predicted BNST Homer2 expression. These data provide support for the regulation of alcohol consumption by mGlu5 across sexes.
Assuntos
Consumo Excessivo de Bebidas Alcoólicas/prevenção & controle , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Núcleo Accumbens/efeitos dos fármacos , Piridinas/uso terapêutico , Núcleos Septais/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Proteínas de Arcabouço Homer/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Núcleo Accumbens/metabolismo , Piridinas/farmacologia , Receptor de Glutamato Metabotrópico 5/antagonistas & inibidores , Núcleos Septais/metabolismo , Caracteres SexuaisRESUMO
ISSUE ADDRESSED: Social media, while available to parents to inform decisions about their child's health, including immunisation, is a new area of exploration in public health. To effectively source, interpret and use such information, parents need to be health literate. This pilot study explored how parents of young children under 7 years of age obtained, understood and used immunisation information available through social media to inform immunisation decisions for their children. METHODS: Purposive sampling followed by a snowball technique was used to recruit parents with one or more children under 7 years of age living in the Brisbane North and Sunshine Coast regions, Australia. Face-to-face interviews collected qualitative data in relation to how parents obtained, understood and used information sourced via social media to make immunisation decisions for their children. RESULTS: All participants were passively exposed to immunisation information on social media through Facebook, YouTube, Instagram, Pinterest, LinkedIn and Twitter, but did not report proactively searching for information. The majority understood the immunisation information obtained, however, did not perceive it as credible and used other sources to clarify credibility, including their health care professional. Some participants interacted with the information, but none used it to make immunisation decisions for their children. CONCLUSIONS: Whilst parents of children under 7 years of age are exposed to immunisation information on social media, they do not use this information to make immunisation decisions for their children, and rely on health care professionals for credible information. SO WHAT?: Given health care providers are perceived by parents of young children as credible sources of immunisation information and parents are regularly exposed to immunisation information via social media, further exploration of the potential role of health care professionals in the dissemination of credible immunisation information via social media platforms is warranted.
Assuntos
Mídias Sociais , Criança , Pré-Escolar , Humanos , Imunização , Pais , Projetos Piloto , VacinaçãoRESUMO
Flexible decision-making in dynamic environments requires both retrospective appraisal of reinforced actions and prospective reasoning about the consequences of actions. These complementary reinforcement-learning systems can be characterized computationally with model-free and model-based algorithms, but how these processes interact at a neurobehavioral level in normal and pathological states is unknown. Here, we developed a translationally analogous multistage decision-making (MSDM) task to independently quantify model-free and model-based behavioral mechanisms in rats. We provide the first direct evidence that male rats, similar to humans, use both model-free and model-based learning when making value-based choices in the MSDM task and provide novel analytic approaches for independently quantifying these reinforcement-learning strategies. Furthermore, we report that ex vivo dopamine tone in the ventral striatum and orbitofrontal cortex correlate with model-based, but not model-free, strategies, indicating that the biological mechanisms mediating decision-making in the multistage task are conserved in rats and humans. This new multistage task provides a unique behavioral platform for conducting systems-level analyses of decision-making in normal and pathological states.SIGNIFICANCE STATEMENT Decision-making is influenced by both a retrospective "model-free" system and a prospective "model-based" system in humans, but the biobehavioral mechanisms mediating these learning systems in normal and disease states are unknown. Here, we describe a translationally analogous multistage decision-making task to provide a behavioral platform for conducting neuroscience studies of decision-making in rats. We provide the first evidence that choice behavior in rats is influenced by model-free and model-based systems and demonstrate that model-based, but not model-free, learning is associated with corticostriatal dopamine tone. This novel behavioral paradigm has the potential to yield critical insights into the mechanisms mediating decision-making alterations in mental disorders.
Assuntos
Comportamento Animal/fisiologia , Química Encefálica/fisiologia , Tomada de Decisões/fisiologia , Algoritmos , Animais , Condicionamento Operante/fisiologia , Dopamina/fisiologia , Masculino , Modelos Psicológicos , Modelos Estatísticos , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiologia , Ratos , Ratos Long-Evans , Estriado Ventral/metabolismo , Estriado Ventral/fisiologiaRESUMO
Individuals with alcohol use disorder exhibit compulsive habitual behaviors that are thought to be, in part, a consequence of chronic and persistent use of alcohol. The endocannabinoid system plays a critical role in habit learning and in ethanol self-administration, but the role of this neuromodulatory system in the expression of habitual alcohol seeking is unknown. Here, we investigated the role of the endocannabinoid system in established alcohol habits using contingency degradation in male C57BL/6 mice. We found that administration of the novel diacyl glycerol lipase inhibitor DO34, which decreases the biosynthesis of the endocannabinoid 2-arachidonoyl glycerol (2-AG), reduced habitual responding for ethanol and ethanol approach behaviors. Moreover, administration of the endocannabinoid transport inhibitor AM404 or the cannabinoid receptor type 1 antagonist AM251 produced similar reductions in habitual responding for ethanol and ethanol approach behaviors. Notably, AM404 was also able to reduce ethanol seeking and consumption in mice that were insensitive to lithium chloride-induced devaluation of ethanol. Conversely, administration of JZL184, a monoacyl glycerol lipase inhibitor that increases levels of 2-AG, increased motivation to respond for ethanol on a progressive ratio schedule of reinforcement. These results demonstrate an important role for endocannabinoid signaling in the motivation to seek ethanol, in ethanol-motivated habits, and suggest that pharmacological manipulations of endocannabinoid signaling could be effective therapeutics for treating alcohol use disorder.
Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Ácidos Araquidônicos/metabolismo , Endocanabinoides/metabolismo , Glicerídeos/metabolismo , Hábitos , Motivação , Animais , Ácidos Araquidônicos/biossíntese , Ácidos Araquidônicos/farmacologia , Benzodioxóis/farmacologia , Antagonistas de Receptores de Canabinoides/farmacologia , Depressores do Sistema Nervoso Central , Comportamento de Procura de Droga , Endocanabinoides/biossíntese , Etanol , Glicerídeos/biossíntese , Lipase Lipoproteica/antagonistas & inibidores , Cloreto de Lítio/farmacologia , Camundongos , Monoacilglicerol Lipases/antagonistas & inibidores , Piperidinas/farmacologia , Pirazóis/farmacologia , Receptor CB1 de Canabinoide/antagonistas & inibidoresRESUMO
BACKGROUND: Insufficient sleep is associated with increased risk of chronic diseases, substance use, and unintentional injuries. Little is known about the disparities in short sleep among sexual minority youth. METHODS: A nationally representative sample of U.S. students in grades 9-12 (n = 14,703) from the 2015 Youth Risk Behavior Survey was analyzed to examine the prevalence and risk factors of short sleep. Self-reported sleep duration (very short: ≤5 h, short: 6-7 h, normal: ≥8 h per day) were compared by sex group (male vs. female) and sexual orientation (heterosexual, gay, lesbian, bisexual, and unsure). RESULTS: Of all respondents, 88.8% were heterosexual/straight, 2.0% were lesbian or gay, 6.0% were bisexual, and 3.2% were unsure about their sexual identity. Bisexual and unsure girls (36.2%, 95% CI [31.3-41.0] and 33.7%, CI [25.6-41.8], respectively) had a higher prevalence of very short sleep duration than straight girls (19.8%, CI [18.3-21.4]). Gay and unsure boys (38.5%, CI [25.6-51.5] and 33.3%, CI [23.5-32.1], respectively) had a higher prevalence of very short sleep duration than straight boys (16.5%, CI [15.1-17.9]). The effects of sexual minority status on very short sleep duration attenuated when incrementally adjusting for influencing factors, and further analysis identified that feeling sad/hopeless had the largest standardized mediation effect. CONCLUSIONS AND RELEVANCE: Sexual minority adolescents had a higher prevalence of reporting very short sleep duration as compared to their straight peers, and the effects were mediated by influencing variables including demographic factors, substance use, excessive media use, and experiences of victimization/mental health problems.
Assuntos
Minorias Sexuais e de Gênero/psicologia , Transtornos do Sono-Vigília/epidemiologia , Adolescente , Feminino , Disparidades em Assistência à Saúde/normas , História do Século XXI , Humanos , Masculino , Estados UnidosRESUMO
Historically, simulation-based dental education was taught using practical skills and the action of doing. An increased awareness of the importance of patient safety in healthcare education and delivery has seen considerable advances in the application of simulation-based education across several healthcare disciplines including medicine, nursing and anaesthetics. Dental simulation-based education requires improved standards of best-practice, and evidence-based, curriculum design that is based on theoretical frameworks, conceptual frameworks and educational theories. In this commentary, we explore the educational theory and the development of healthcare simulation, including internationally recognised standards of best practice and the simulation-based activity cycle. Given simulation-based education should be fit-for purpose, the components of these standards are examined within the specific context of dental education. We propose an evidence-based, best-practice framework that can be applied in the design and delivery of contemporary simulation-based dental curriculum.
Assuntos
Competência Clínica , Educação em Odontologia , Simulação por Computador , Currículo , Humanos , TempoRESUMO
The compulsive, habitual behaviors that have been observed in individuals diagnosed with substance use disorders may be due to disruptions in the neural circuits that mediate goal-directed actions. The endocannabinoid system has been shown to play a critical role in habit learning, but the role of this neuromodulatory system in habit expression is unclear. Here, we investigated the role of the endocannabinoid system in established habitual actions using contingency degradation in male C57BL/6 mice. We found that administration of the endocannabinoid transport inhibitor AM404 reduced habitual responding for food and that antagonism of cannabinoid receptor type 1 (CB1), but not transient receptor potential cation subfamily V (TRPV1), receptors produced a similar reduction in habitual responding. Moreover, pharmacological stimulation of CB1 receptors increased habitual responding for food. Co-administration of an enzyme inhibitor that selectively increases the endocannabinoid 2-arachidonoyl glycerol (2-AG) with AM404 partially restored habitual responding for food. Together, these findings demonstrate an important role for the endocannabinoid system in the expression of habits and provide novel insights into potential pharmacological strategies for reducing habitual behaviors in mental disorders.