A locus coeruleus to dorsal hippocampus pathway mediates cue-induced reinstatement of opioid self-administration in male and female rats.

Opioid use disorder is a chronic relapsing disorder encompassing misuse, dependence, and addiction to opioid drugs. Long term maintenance of associations between the reinforcing effects of the drug and the cues associated with its intake are a leading cause of relapse. Indeed, exposure to the salient drug-associated cues can lead to drug cravings and drug seeking behavior. The dorsal hippocampus (dHPC) and locus coeruleus (LC) have emerged as important structures for linking the subjective rewarding effects of opioids with environmental cues. However, their role in cue-induced reinstatement of opioid use remains to be further elucidated. In this study, we showed that chemogenetic inhibition of excitatory dHPC neurons during re-exposure to drug-associated cues significantly attenuates cue-induced reinstatement of morphine-seeking behavior. In addition, the same manipulation reduced reinstatement of sucrose-seeking behavior but failed to alter memory recall in the object location task. Finally, intact activity of tyrosine hydroxylase (TH) LC-dHPCTh afferents is necessary to drive cue induced reinstatement of morphine-seeking as inhibition of this pathway blunts cue-induced drug-seeking behavior. Altogether, these studies show an important role of the dHPC and LC-dHPCTh pathway in mediating cue-induced reinstatement of opioid seeking.

Validación del inventario de capacidades emocionales en adolescentes (ICEA)

RESUMEN Fundamento dada las características de la adolescencia donde ocurren importantes cambios, no solo a nivel fisiológico sino también psicológico, las capacidades emocionales adquieren gran relevancia. Estas permiten un mayor ajuste psicológico y bienestar, mayor calidad en las relaciones interpersonales, mejor rendimiento escolar y menos conductas disruptivas, depresión y ansiedad. Objetivo: construir y validar el Inventario de Capacidades Emocionales en Adolescentes. Métodos la investigación se realizó en dos etapas; en la primera participaron 419 adolescentes y nueve expertos que valoraron la validez de contenido y constructo del instrumento. En la segunda etapa con una muestra de 291 adolescentes se realizó la validación de criterio concurrente del inventario con las medidas de Bienestar Psicológico (BIEPS-J), con el Inventario de Ansiedad Rasgo-Estado (IDARE-N) y el Inventario de Depresión Rasgo-Estado (IDERE-N). Resultados: a partir del juicio de expertos y el análisis factorial se obtuvo un instrumento de 43 incisos con una estructura multidimensional de cinco factores, las cuales se corresponden con las capacidades emocionales descritas en el modelo de Goleman: autoconocimiento, autocontrol, automotivación, empatía y manejo de relaciones. Se obtienen correlaciones positivas y moderadas con la escala BIEPS-J; negativas y moderadas con el IDARE-N, negativas y moderadas con la depresión como rasgo y negativas y débiles con la depresión como estado. La consistencia interna es elevada (Alfa de Cronbach = .86) Conclusiones se logra la construcción de una medida de evaluación de capacidades emocionales en adolescentes que posee validez de contenido, de constructo y de criterio, así como una alta confiabilidad y consistencia interna.

ABSTRACT Background: given the characteristics of adolescence where important changes occur not only at a physiological level but also at a psychological level, emotional capacities acquire great relevance. These allow for greater psychological adjustment and well-being, higher quality in interpersonal relationships, better school performance and fewer disruptive behaviors, depression and anxiety. Objective: Build and validate the Inventory of Emotional Capacities in Adolescents. Methods: The investigation was carried out in two stages; 419 adolescents and 9 experts participated in the first, who assessed the content and construct validity of the instrument. In the second stage, with a sample of 291 adolescents, the concurrent criterion validation of the ICEA was carried out with the measures of Psychological Well-being (BIEPS-J), with the Trait-State Anxiety Inventory (IDARE-N) and the Trait Depression Inventory -State (IDERE-N). Results: From the judgment of experts and the factor analysis, an instrument of 43 items is obtained with a multidimensional structure of 5 factors, which correspond to the emotional capacities described in the Goleman model: self-knowledge, self-control, self-motivation, empathy and relationship management. Positive and moderate correlations are obtained with the BIEPS-J scale; negative and moderate with the IDARE-N, negative and moderate with depression as a trait and negative and weak with depression as a state. Internal consistency is high (Cronbach's Alpha = .86) Conclusions: The construction of a measure of evaluation of emotional capacities in adolescents is achieved that has content, construct and criterion validity, as well as high reliability and internal consistency.

Factores pronósticos que afectan la supervivencia en el paciente con mieloma múltiple / Prognostic factors affecting survival in the patient with multiple myeloma

Resumen El mieloma múltiple es la segunda neoplasia hematológica más frecuente y se caracteriza por la expansión aberrante de las células plasmáticas monoclonales, en la mayoría de los casos con la producción de una paraproteína anormal conocida como proteína monoclonal o por evidencia de daño orgánico, manifestado por hipercalcemia, insuficiencia renal, anemia o lesiones óseas. Los factores pronósticos han evolucionado desde la caracterización de la carga tumoral utilizando el sistema de estadificación Durie y Salmon y el sistema de estadificación internacional, hasta el análisis molecular y el perfil de expresión génica, debido al reconocimiento de aberraciones cromosómicas y moleculares que desempeñan un papel en el desarrollo del mieloma múltiple y la progresión del mismo. El sistema de estadificación internacional se revisó en 2015 agregando anormalidades genéticas de alto riesgo, tales como la presencia de mutaciones t(4;14), t(14;16) y del(17p) junto con la adición de la deshidrogenasa láctica. Es así como, a lo largo del tiempo, se han identificado factores pronósticos importantes de esta neoplasia que se encuentran asociados al huésped y al microambiente tumoral, además de variables clínicas y anormalidades de las células tumorales.

Abstract Multiple myeloma is the second most frequent hematological neoplasm, characterized by the aberrant expansion of monoclonal plasma cells, in most cases with the production of an abnormal paraprotein known as monoclonal protein and/or evidence of organic damage manifested by hypercalcemia, renal failure, anemia and/or bone lesions. Prognostic factors have evolved from the characterization of tumor burden using the Durie and Salmon and International Staging System, to molecular analysis and gene expression profiling due to the recognition of chromosomal and molecular aberrations, which play a role in the development of multiple myeloma and its progression. The International Staging System was revised in 2015 by adding high risk genetic abnormalities such as the presence of t(4;14), t(14;16) and del (17p) mutations along with the addition of lactic dehydrogenase. Thus, over time, important prognostic factors of this neoplasm have been identified that are associated with the host and the tumor microenvironment, in addition to clinical variables and abnormalities of the tumor cells.

Pain induces adaptations in ventral tegmental area dopamine neurons to drive anhedonia-like behavior.

The persistence of negative affect in pain leads to co-morbid symptoms such as anhedonia and depression-major health issues in the United States. The neuronal circuitry and contribution of specific cellular populations underlying these behavioral adaptations remains unknown. A common characteristic of negative affect is a decrease in motivation to initiate and complete goal-directed behavior, known as anhedonia. We report that in rodents, inflammatory pain decreased the activity of ventral tegmental area (VTA) dopamine (DA) neurons, which are critical mediators of motivational states. Pain increased rostromedial tegmental nucleus inhibitory tone onto VTA DA neurons, making them less excitable. Furthermore, the decreased activity of DA neurons was associated with reduced motivation for natural rewards, consistent with anhedonia-like behavior. Selective activation of VTA DA neurons was sufficient to restore baseline motivation and hedonic responses to natural rewards. These findings reveal pain-induced adaptations within VTA DA neurons that underlie anhedonia-like behavior.

Effects of inflammatory pain on CB1 receptor in the midbrain periaqueductal gray.

INTRODUCTION: The periaqueductal gray (PAG) mediates the antinociceptive properties of analgesics, including opioids and cannabinoids. Administration of either opioids or cannabinoids into the PAG induces antinociception. However, most studies characterizing the antinociceptive properties of cannabinoids in the PAG have been conducted in naive animals. Few studies have reported on the role of CB1 receptors in the PAG during conditions which would prompt the administration of analgesics, namely, during pain states. OBJECTIVES: To examine inflammatory pain-induced changes in CB1 receptor expression and function in the midbrain periaqueductal gray. METHODS: In this study, we used the Complete Freund Adjuvant model to characterize CB1 receptor expression and G-protein coupling during persistent inflammatory pain. RESULTS: Inflammatory pain induced an upregulation in the expression of synaptic CB1 receptors in the PAG. Despite this pain-induced change in CB1 expression, there was no corresponding upregulation of CB1 mRNA after the induction of inflammatory pain, suggesting a pain-induced recruitment of CB1 receptors to the synaptic sites within PAG neurons or increased coupling efficiency between the receptor and effector systems. Inflammatory pain also enhanced ventrolateral PAG CB1 receptor activity, as there was an increase in CP55,940-stimulated G-protein activation compared with pain-naïve control animals. CONCLUSION: These findings complement a growing body of evidence which demonstrate pain-induced changes in brain regions that are responsible for both the analgesic and rewarding properties of analgesic pharmacotherapies. Because much of our understanding of the pharmacology of cannabinoids is based on studies which use largely pain-naïve male animals, this work fills in important gaps in the knowledge base by incorporating pain-induced adaptations and cannabinoid pharmacology in females.

Morphometric and computational assessments to evaluate neuron survival and maturation within compartmentalized microfluidic devices: The influence of design variation on diffusion-driven nutrient transport.

Burgeoning use of segregated microfluidic platforms that parse somas and neurites into discrete compartments is fueling unique examinations of neuronal structure and physiology in a manner impossible to achieve with non-compartmentalized systems. However, even though this line of axon-soma polarizing microfluidic devices stems from the same general design of a Campenot chamber set-up, slight deviations in device geometry appear to induce vastly different nutrient transport profiles that influence neuron survival and maturation. Here we examine the uptake of nerve growth factor (NGF) by a pheochromocytoma PC12 cell line cultured using two Campenot-like device designs, a "Standard" layout, representative of a commercial device, and a custom "Notch" layout, predicted to encourage more efficient nutrient transfer that gives rise to sustained neuron viability and extensive neurite elaboration. Exploiting in vitro culture schemes coupled with computational analyses, we identify the influence of device design geometry on the interplay between neuronal survival and maturation, gauged from morphometric assessments and the spatiotemporal distribution of NGF. Computer simulations of NGF transport within the devices revealed that the microfluidic neuron culture system is highly sensitive to change, where nutrient transport is intricately linked to device geometry and cell plating density, and premature depletion of nutrients is observed if specific design criteria are not met. This study underscores the importance of validating specific device geometries for a particular neuro-based assessment, while showcasing computational modeling as a powerful tool to achieve this goal.