Enhancing translation: A need to leverage complex preclinical models of addictive drugs to accelerate substance use treatment options.

Preclinical models of addictive drugs have been developed for decades to model aspects of the clinical experience in substance use disorders (SUDs). These include passive exposure as well as volitional intake models across addictive drugs and have been utilized to also measure withdrawal symptomatology and potential neurobehavioral mechanisms underlying relapse to drug seeking or taking. There are a number of Food and Drug Administration (FDA)-approved medications for SUDs, however, many demonstrate low clinical efficacy as well as potential sex differences, and we also note gaps in the continuum of care for certain aspects of clinical experiences in individuals who use drugs. In this review, we provide a comprehensive update on both frequently utilized and novel behavioral models of addiction with a focus on translational value to the clinical experience and highlight the need for preclinical research to follow epidemiological trends in drug use patterns to stay abreast of clinical treatment needs. We then note areas in which models could be improved to enhance the medications development pipeline through efforts to enhance translation of preclinical models. Next, we describe neuroscience efforts that can be leveraged to identify novel biological mechanisms to enhance medications development efforts for SUDs, focusing specifically on advances in brain transcriptomics approaches that can provide comprehensive screening and identification of novel targets. Together, the confluence of this review demonstrates the need for careful selection of behavioral models and methodological parameters that better approximate the clinical experience combined with cutting edge neuroscience techniques to advance the medications development pipeline for SUDs.

Avoidance and fear day by day in social anxiety disorder.

OBJECTIVE: Theories assert that avoidance maintains maladaptive anxiety over time, yet a clear prospective test of this effect in the day-by-day lives of people with social anxiety disorder (SAD) is lacking. METHOD: We used intensive longitudinal data to test prospective relationships between social fear and social avoidance in 32 participants with SAD who reported on a total of 4256 time points. RESULTS: Results suggested that avoidance strongly predicted future anxiety, but only in a minority of people with SAD. Relationships between anxiety and avoidance varied considerably across individuals. Pre-registered tests found that the strength of autocorrelation for social fear is a good target for future testing of prediction of exposure response. Participants with lower autocorrelations were less likely to show between-session habituation. CONCLUSIONS: Overall, results suggest avoidance maintains fear in SAD for at least some individuals, but also indicates considerable variability. Further intensive longitudinal data is needed to examine individuals with SAD across varying time courses.

The Overview of Cognitive Aging Models.

To understand the cause of the age-related decline in cognitive function and its underlying mechanism, the cognitive aging model can provide us with important insights. In this section, we will introduce behavioral and neural models about age-related cognitive changes. Among behavioral models, several aging theories were discussed from the perspectives of educational, biological, and sociological factors, which could explain parts of the aging process. With the development of imaging technology, many studies have discussed the neural mechanism of aging and successively proposed neural models to explain the aging phenomenon. Behavioral models and neural mechanism models supplement each other, gradually unveiling the mystery of cognitive aging.

Post-partum depression: From clinical understanding to preclinical assessments.

Post-partum depression (PPD) with varying clinical manifestations affecting new parents remains underdiagnosed and poorly treated. This minireview revisits the pharmacotherapy, and relevant etiological basis, capable of advancing preclinical research frameworks. Maternal tasks accompanied by numerous behavioral readouts demand modeling different paradigms that reflect the complex and heterogenous nature of PPD. Hence, effective PPD-like characterization in animals towards the discovery of pharmacological intervention demands research that deepens our understanding of the roles of hormonal and non-hormonal components and mediators of this psychiatric disorder.

Integrating basic and applied research to estimate carnivore abundance.

A clear connection between basic research and applied management is often missing or difficult to discern. We present a case study of integration of basic research with applied management for estimating abundance of gray wolves (Canis lupus) in Montana, USA. Estimating wolf abundance is a key component of wolf management but is costly and time intensive as wolf populations continue to grow. We developed a multimodel approach using an occupancy model, mechanistic territory model, and empirical group size model to improve abundance estimates while reducing monitoring effort. Whereas field-based wolf counts generally rely on costly, difficult-to-collect monitoring data, especially for larger areas or population sizes, our approach efficiently uses readily available wolf observation data and introduces models focused on biological mechanisms underlying territorial and social behavior. In a three-part process, the occupancy model first estimates the extent of wolf distribution in Montana, based on environmental covariates and wolf observations. The spatially explicit mechanistic territory model predicts territory sizes using simple behavioral rules and data on prey resources, terrain ruggedness, and human density. Together, these models predict the number of packs. An empirical pack size model based on 14 years of data demonstrates that pack sizes are positively related to local densities of packs, and negatively related to terrain ruggedness, local mortalities, and intensity of harvest management. Total abundance estimates for given areas are derived by combining estimated numbers of packs and pack sizes. We estimated the Montana wolf population to be smallest in the first year of our study, with 91 packs and 654 wolves in 2007, followed by a population peak in 2011 with 1252 wolves. The population declined ~6% thereafter, coincident with implementation of legal harvest in Montana. Recent numbers have largely stabilized at an average of 191 packs and 1141 wolves from 2016 to 2020. This new approach accounts for biologically based, spatially explicit predictions of behavior to provide more accurate estimates of carnivore abundance at finer spatial scales. By integrating basic and applied research, our approach can therefore better inform decision-making and meet management needs.

A comparison of seasonal influenza and novel Covid-19 vaccine intentions: A cross-sectional survey of vaccine hesitant adults in England during the 2020 pandemic.

We compared intention to receive the seasonal influenza vaccine with a prospective coronavirus (COVID-19) vaccine among undecided or COVID-19 vaccine hesitant individuals to better understand the underlying differences and similarities in factors associated with vaccine intention. We delivered a cross-sectional online survey in October-November 2020. We included psychological constructs and sociodemographic variables informed by theory. We conducted pairwise comparisons and multiple linear regression models to explore associations between vaccine intention and psychological constructs. We recruited 1,660 participants, where 47.6% responded that they would likely receive the influenza vaccine, 31.0% that they would probably not accept the vaccination and 21.4% were unsure. In relation to the prospective COVID-19 vaccine, 39.0% responded that they would likely receive the vaccination, 23.7% that they would probably not accept the vaccination and 37.3% were unsure. Unique factors positively associated with COVID-19 vaccine intention were: perceived knowledge sufficiency about vaccine safety, beliefs about vaccine safety, and living in an area of low deprivation. The only unique factor positively associated with influenza intention was past influenza behavior. The strongest common predictors positively associated with intention were: favorable vaccine attitudes, the anticipated regret they may feel following infection if they were not to receive a vaccine, and the expectation from family or friends to accept the vaccine. Despite overall similarities in those factors associated with vaccination intention, we identified unique influences on intention. This additional insight will help support the planning and tailoring of future immunizations programmes for the respective viruses.

Learning from experience: Within- and between-person associations of the consequences, frequency, and versatility of nonsuicidal self-injury.

OBJECTIVE: Behavioral models of nonsuicidal self-injury (NSSI) propose that experiencing desirable consequences following NSSI reinforces the behavior. However, these models do not specify whether experiencing more desirable consequences relative to other people (between-person), an individual's own average (within-person), or both, predicts NSSI severity. To address this gap, this study investigated the prospective, within- and between-person associations of desirable NSSI consequences with NSSI frequency (number of episodes) and versatility (number of methods). METHODS: Two hundred and ten individuals (93.81% female, Mage  = 22.95) with a history of NSSI completed online surveys assessing NSSI consequences, frequency, and versatility every three months for one year. RESULTS: Within-person increases in desirable emotional consequences were unrelated to NSSI frequency three months later but predicted increases in NSSI versatility. Within-person increases in desirable social consequences predicted decreases in NSSI frequency three months later but were unrelated to NSSI versatility. Between-person variability in desirable consequences was unrelated to NSSI severity. CONCLUSIONS: Findings were partially consistent with behavioral models of NSSI. Going forward, we recommend that: (1) behavioral models articulate the salience of within-person fluctuations in consequences; (2) research clarifies the role of social consequences; and (3) clinicians use repeated assessments of emotional consequences to identify periods of elevated NSSI risk.

Hacia un enfoque multinivel en los estudios empíricos de la empatía: autopercepción, comportamiento y mecanismos neurobiológicos / Towards a multilevel approach in empirical studies of empathy: self-perception, behavior and neurobiological mechanisms

La empatía es un fenómeno multifacético necesario para la interacción social. La complejidad de su estudio se origina en la multiplicidad de definiciones teóricas y en los distintos niveles de análisis. Aunque existen numerosas revisiones metodológicas, son escasas las que comprenden la autopercepción, el comportamiento y los mecanismos neurobiológicos. Por este motivo, el objetivo de este artículo es realizar un análisis crítico de las metodologías mayormente utilizadas, agrupadas en distintos niveles de análisis. El nivel de autopercepción incluye escalas de autorreporte; el comportamental contempla modelos de simulaciones, presentación de imágenes, filmaciones y narrativas; y el neurobiológico comprende indicadores del sistema nervioso periférico (electrocardiograma, actividad electrodérmica y electromiograma) y central (electroencefalograma y resonancia magnética funcional), y abordajes farmacológicos, neuroquímicos y génicos. Analizamos los procesos afectivos, cognitivos y motivacionales, así como las ventajas y desventajas de cada metodología. Por último, planteamos propuestas integrativas y formulamos preguntas que podrían guiar investigaciones futuras.

Empathy is a multifaceted phenomenon necessary for social interaction. The complexity of its study resides in the multiplicity of theoretical definitions and in the different levels of analysis. Even though there are numerous methodological reviews, those that take into account self-perceived and behavioral levels together with neurobiological mechanisms are scarce. For this reason, the aim of this revision is to perform a critical analysis of different methodologies within different levels of analysis. The self-perception level included self reported scales, the behavioral level comprises simulation models, images or film presentations and narratives, and the neurobiological level included peripheral (electrocardiogram, electrodermal activity and electromyogram) and central nervous system (electroencephalogram and functional magnetic resonance imaging) indicators, and pharmacological, neurochemical and genic approaches. We analysed the affective, cognitive and motivational processes as well as the advantages and disadvantages of each methodology. Finally, we pose some integrative proposals and questions that could guide future research.

1H-1,2,3-triazole grafted tacrine-chalcone conjugates as potential cholinesterase inhibitors with the evaluation of their behavioral tests and oxidative stress in mice brain cells.

The present paper explicates the synthesis of 1H-1,2,3-triazole tethered tacrine-chalcone conjugates and evaluation of their AChE and BuChE inhibitory activity. In-vitroAChE inhibition assay revealed three compounds, 9h, 9i, and 11f, being more potent than the standard drug tacrine and further evaluated against butyrylcholinesterase. The present study was extended to investigate the anti-amnestic effect of promising compoundson scopolamine-induced behavioral and neurochemical changes in mice. Inclined plane model and Elevated plus-maze model were performed to assess general limb motor activity and anxiety-like behavior, respectively, in mice pre-treated with scopolamine. Oxidative stress parameters reduced glutathione contents (GSH) and lipid peroxidation products (TBARS) in the brain homogenates as estimated using ex-vivo studies. Furthermore, molecular docking studies were performed for the potent compounds to decipher the mechanism of observed activities.

Biofabricated zinc oxide nanoparticles impair cognitive function via modulating oxidative stress and acetylcholinesterase level in mice.

Current work was designed to explore the effect of ZnO nanoparticles (ZnONP) biofabricated by using Trianthema portulacastrum (TP) leaves extract on mice brain hippocampus. ZnO nanoparticles of TP leaves (ZnOTP) were synthesized by co-precipitation method and further characterized by using various techniques such as UV-Vis spectrophotometer, Field Emission Scanning Electron Microscopy (FESEM), Fourier Transform Infrared (FTIR), and Energy Dispersive X-ray (EDX). ZnOTP were evaluated for in vitro antioxidant activity, in vivo behavior models (for assessment of cognitive ability), acetylcholinesterase (AChE) activity along with other neurotransmitters content determination, estimation of various oxidative stress parameters and analysis of zinc content in the brain as well as plasma. Histopathological evaluation of the brain hippocampus of each group was performed to corroborate the statistical results. Spherical ZnOTP of 10 to 20 nm size embedded with different phytoconstituents of TP was confirmed. Results of our study revealed a significant memory deficit in mice treated with ZnOTP. Neuronal degeneration was also observed via a significant increase in AChE activity and oxidative stress levels in the brain of mice administered with ZnOTP. Exposure of ZnOTP was also found responsible for modulation of neurotransmission in hippocampus area. Further, ZnOTP disturbed the zinc homeostasis in hippocampus via elevation of zinc content in brain as well as plasma. Histopathology of hippocampus supported the damaging impact of ZnOTP by an increase in vacuolated cytoplasm and focal gliosis in groups treated with ZnOTP. Results demonstrated the neurotoxic effect of ZnOTP on brain hippocampus via cognitive impairment by alteration of neurotransmitter level, zinc content and oxidative stress.

Educational and Behavioral Models for Promoting Health in Saudi Arabia: A Theoretical Overview.

In recent years, the field of environmental health promotion gained new prominence as awareness of physical environmental stressors and exposures escalated in Saudi Arabia. Although, several theories and conceptual models are routinely used for guiding health education and promotion interventions, they are rarely applied to environmental health issues in Saudi Arabia. This study theoretically reviews the educational and behavioral models for promoting health in Saudi Arabia. This study examines how education and behavioral models can reduce exposure to environmental health risks. In particular, this article describes the application of ecological theory with regard to its theoretical, analytical, and methodological challenges to future research in educational and behavioral studies. The implications of ecological theory are discussed for environmental health promotion. Ecological theory can further demonstrate the dimensions of health behaviors such as procedures for changing them. Health behaviors are also affected by many forces such as physical and social environments. This theory can assist planners in identifying the most appropriate target audiences, methods to improve change, and consequences for assessment. This theory is also important in including social, cultural, and physical factors that affect health consequences, which include factors such as social cohesion, behavioral patterns, emotional wellbeing, genetic heritage, and developmental maturation.

Experimental Anxiety Model for Anxiety Disorders: Relevance to Drug Discovery.

This chapter describes the various animal models that seem relevant to the development of anxiolytic drugs, as well as the human models of induced anxiety, or more precisely the panic inducers including cholecystokinin. It is also mentioned the theoretical model of Deakin and Graeff which seems to keep all its relevance. The knock animals are evoked as relevant tools as well as a new optogenetic technique that needs to be used in this field.

Probabilistic Models of Larval Zebrafish Behavior Reveal Structure on Many Scales.

Nervous systems have evolved to combine environmental information with internal state to select and generate adaptive behavioral sequences. To better understand these computations and their implementation in neural circuits, natural behavior must be carefully measured and quantified. Here, we collect high spatial resolution video of single zebrafish larvae swimming in a naturalistic environment and develop models of their action selection across exploration and hunting. Zebrafish larvae swim in punctuated bouts separated by longer periods of rest called interbout intervals. We take advantage of this structure by categorizing bouts into discrete types and representing their behavior as labeled sequences of bout types emitted over time. We then construct probabilistic models-specifically, marked renewal processes-to evaluate how bout types and interbout intervals are selected by the fish as a function of its internal hunger state, behavioral history, and the locations and properties of nearby prey. Finally, we evaluate the models by their predictive likelihood and their ability to generate realistic trajectories of virtual fish swimming through simulated environments. Our simulations capture multiple timescales of structure in larval zebrafish behavior and expose many ways in which hunger state influences their action selection to promote food seeking during hunger and safety during satiety.

CUBES: A practical toolkit to measure enablers and barriers to behavior for effective intervention design.

A pressing goal in global development and other sectors is often to understand what drives people's behaviors, and how to influence them. Yet designing behavior change interventions is often an unsystematic process, hobbled by insufficient understanding of contextual and perceptual behavioral drivers and a narrow focus on limited research methods to assess them. We propose a toolkit (CUBES) of two solutions to help programs arrive at more effective interventions. First, we introduce a novel framework of behavior, which is a practical tool for programs to structure potential drivers and match corresponding interventions. This evidence-based framework was developed through extensive cross-sectoral literature research and refined through application in large-scale global development programs. Second, we propose a set of descriptive, experimental, and simulation approaches that can enhance and expand the methods commonly used in global development. Since not all methods are equally suited to capture the different types of drivers of behavior, we present a decision aid for method selection. We recommend that existing commonly used methods, such as observations and surveys, use CUBES as a scaffold and incorporate validated measures of specific types of drivers in order to comprehensively test all the potential components of a target behavior. We also recommend under-used methods from sectors such as market research, experimental psychology, and decision science, which programs can use to extend their toolkit and test the importance and impact of key enablers and barriers. The CUBES toolkit enables programs across sectors to streamline the process of conceptualizing, designing, and optimizing interventions, and ultimately to change behaviors and achieve targeted outcomes.

Data of thematic analysis of farmer׳s use behavior of recycled industrial wastewater.

Farmers are concerned in the chemical supply chain (manufacturers, vendors, workers, and consumers) of the agricultural products through their understandings of the safety information (i.e. reading labels such as skull and crossbones symbols, volatile organic compound logo or the fish and tree symbol) and the factors influence misuse of irrigation and disposal behavior. Having recognized a methodological gap, this contribution was intended to investigate qualitatively (textural analysis) the determinants of the use behavior (UB) of farmers irrigating their lands by the recycled industrial wastewater (RIWW) (Aljerf, 2018) [1] using the exploratory investigation based on the single embedded case design. Such combined analytical methods enabled us to achieve both detailed insights into perceptions, behaviors, and an objective understanding of the prevailing opinions that occurred within and between the focus farmers group׳ discussions related around awareness, trust, access and disposal actions within the supply chain. Using the snowball sampling approach, verbal data were collected from 55 Syrian farmers. 5 × 11,000 US gallons (43,900 L) of the RIWW were delivered to each farmer upon request between May and October 2017. After a month of each distribution, the participant farmer was interviewed. To increase the validity of the data, method triangulation was implemented which encompassed participant observation, group debates, and unstructured interviews. The hermeneutic units were analyzed using the pattern-matching method in the Atlas.ti software (version 6.0.15) and the grounded concepts (determinants) were investigated to establish the hypothetical framework at three levels: intrapersonal, interpersonal, and institutional.

Neuroepigenetics of Neurotrophin Signaling: Neurobiology of Anxiety and Affective Disorders.

This review examines the epigenetic of neurotrophin signaling in anxiety, affective disorders and related symptoms associated with drug addiction, in particular alcoholism. It is first important to understand the epigenetics of aversion memories, as they are so central to anxiety and affective disorders symptomology. The crucial role of neurotrophins in memory formation, in particular the brain-derived nerve growth factor (BDNF), is explored at the physiological and behavioral levels. Numerous studies describe how various epigenetic phenomena, mainly histone acetylation, histone methylation, DNA methylation, but also other less known epigenetic phenomena such as histone poly[ADP]-ribosylation and 5-HT2C receptor pre-mRNA editing, exert significant regulatory roles in aversion memory and fear extinction memory formation. Other models of anxiety and affective disorders, that use stress or transgenic constructs directed at elements of the stress axis or the serotonergic system, are then explored in relation with the epigenetic of neurotrophin signaling. Epigenetic marks differentially change according to brain areas. In the hippocampus for example, anxious or chronically stressed animals tend to show epigenetic changes that are at the opposite of those observed after memory consolidation following a brief aversive stimulus. Behaviorally relevant epigenetic changes have been found to be reversible by drug treatments. Surprisingly, moderate alcohol consumption may trigger, on the long term, changes of BDNF expression and of its epigenetic elements that are somehow similar to those produced by antidepressant drugs. However, alcohol withdrawal associated with anxiety symptoms has not yet been very well explored. Overall, it appears that a multidisciplinary view on the epigenetics of neurotrophin secretion might bring innovative treatments to psychiatric diseases involving stress and fear memories.

Comparative Evaluation of Prosopis cineraria (L.) Druce and Its ZnO Nanoparticles on Scopolamine Induced Amnesia.

Over recent years, utilization of green synthesized nanomaterials has been widely growing on human body because of its special properties. With the increasing acceptance of nanoparticle approach for various clinical treatments, the biosafety and toxicological effects on the vital organs such as central nervous system, have received more concern. Main focus of this study was to evaluate acute exposure of n-butanol fraction of Prosopis cineraria (L.) Druce hydroethanolic extract (BuPC) and green synthesized zinc oxide nanoparticles of BuPC (ZnOPC) on spatial cognition behavior, and to assess underlying mechanism by estimation of enzymatic antioxidative status along with acetylcholinesterase (AChE) activity in mice brain. Strongest in vitro antioxidant and AChE inhibitory activity exhibiting fraction, BuPC, was examined for inhibition kinetic study by Lineweaver-Burk and Dixon plots. BuPC was further used for fabrication ZnOPC and characterized by UV-visible spectroscopy, Fourier Transform Infrared (FTIR), Field Emission Scanning Electron Microscopy (FESEM), Energy Dispersive X ray (EDX), and Dynamic Light Scattering (DLS) analysis. Old male swiss albino mice were randomly divided into seven groups and treated for 21 days. Subsequently spatial memory was determined by two behavioral models [Elevated plus maze (EPM) and Hebbs William maze (HWM)] and supernatant of brain homogenate was analyzed for enzymatic antioxidant level and AChE inhibitory activity. Zinc content of blood plasma and brain was estimated. Results showed prolonged transfer latency (TL) and time taken to reach reward chamber (TRC) by scopolamine was not ameliorated by the ZnOPC group, whereas BuPC group showed significant reduction in scopolamine induced increase in TL and TRC compared to control and scopolamine treated groups. ZnOPC alleviated enzymatic antioxidant activity and AChE as compared to donepezil and BuPC treated groups. Study concludes that ZnOPC attenuated spatial learning and memory by increase in oxidative stress and decrease in AChE activity at both dose levels. Our results suggest that BuPC exhibited a strong neuroprotective effect on cognitive deficit mice and it may be employed as a strong substance for the treatment of dementia whereas the green synthesized ZnOPC was not proficient to reverse the memory impairment induced by scopolamine.

Zebrafish models of autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by motor, social and cognitive deficits that develop early during childhood. The pathogenesis of ASD is not well characterized and involves a multifaceted interaction between genetic, neurobiological and environmental factors. Animal (experimental) models possess evolutionarily conserved behaviors and molecular pathways that are highly relevant for studying ASD. The zebrafish (Danio rerio) is a relatively new animal model with promise for understanding the pathogenesis of complex brain disorders and discovering novel treatments. As a highly social and genetically tractable organism, zebrafish have recently been applied to model a variety of deficits relevant to ASD. Here, we discuss the developing utility of zebrafish models of ASD, as well as current behavioral, toxicological and genetic models of ASD, and future directions of research in this field.

Delta Opioid Pharmacology in Relation to Alcohol Behaviors.

Delta opioid receptors (DORs) are heavily involved in alcohol-mediated processes in the brain. In this chapter we provide an overview of studies investigating how alcohol directly impacts DOR pharmacology and of early studies indicating DOR modulation of alcohol behavior. We will offer a brief summary of the different animal species used in alcohol studies investigating DORs followed by a broader overview of the types of alcohol behaviors modulated by DORs. We will highlight a small set of studies investigating the relationship between alcohol and DORs in analgesia. We will then provide an anatomical overview linking DOR expression in specific brain regions to different alcohol behaviors. In this section, we will provide two models that try to explain how endogenous opioids acting at DORs may influence alcohol behaviors. Next, we will provide an overview of studies investigating certain new aspects of DOR pharmacology, including the formation of heteromers and biased signaling. Finally, we provide a short overview of the genetics of the DORs in relation to alcohol use disorders (AUDs) and a short statement on the potential of using DOR-based therapeutics for treatment of AUDs.

Advantages to Using Social-Behavioral Models of Medication Adherence in Research and Practice.

Achieving and sustaining high levels of adherence to medication regimens is essential to improving health outcomes, but continues to be a challenge for a sizable proportion of patients. Decades of research suggests that medication adherence is determined by a complex constellation of factors. Social-behavioral science research has focused on creating frameworks that identify which contextual, personal, social, or drug-related factors appear to most influence adherence. Comprehensive models of adherence propose specific structural relationships between these factors that can be used to plan for, implement, and monitor programs that seek to optimize adherence. The use of social-behavioral models offers multiple advantages in both practice and research environments; however, the breadth and depth of these models can deter many from engaging in this important exercise. To promote the use of social-behavioral frameworks and models of adherence, we provide a brief overview of the advantages in using a social-behavioral lens in adherence work, a sampling of models used in HIV medication adherence research that have high generalizability to other conditions, and practical guidance for grounding adherence promotion strategies in evidence informed by social-behavioral science research.