Efectos conductuales y neuroquímicos del consumo de éxtasis y cocaína en ratones adolescentes.

La 3,4-metilendioximetanfetamina (MDMA), una sustancia popularmente conocida como éxtasis, es una droga ilícita consumida habitualmente por adolescentes y adultos jóvenes. Además, el policonsumo es una práctica habitual entre los usuarios de la MDMA, siendo la cocaína una de las drogas más frecuentemente asociadas a esta sustancia. El objetivo del presente trabajo fue evaluar los efectos a corto y largo plazo que se producen tras la administración de la MDMA (5, 10, o 20 mg/kg) sola o en combinación con cocaína (25 mg/kg) en ratones adolescentes. En el estudio sobre el efecto agudo, observamos que ambas drogas administradas individual o simultáneamente incrementan la actividad motora. La dosis alta de MDMA disminuye de los contactos sociales en la prueba de la interacción social afectando igualmente el test de retención de la evitación pasiva. Sin embargo, sólo la co-administración de MDMA en combinación con cocaína produjo un efecto ansiolítico caracterizado por un aumento del tiempo de permanencia en los brazos abiertos del laberinto elevado en cruz. Igualmente, el análisis neuroquímico reveló que los ratones que recibieron MDMA en combinación con cocaína mostraron un incremento en el turnover de DA en el estriado, pero una disminución del de serotonina en la corteza. Los estudios de los efectos a largo plazo, realizados tres semanas después de haber finalizado un tratamiento con MDMA sola o en combinación con cocaína (2 administraciones por día durante 3 días consecutivos), mostraron que los ratones expuestos a la MDMA, sola o más cocaína, incrementaron el tiempo dedicado a las conductas sociales, aunque los que también habían recibido cocaína presentaban además conductas de amenaza. Observamos un efecto neurotóxico en los ratones tratados únicamente con 20 mg/kg de MDMA que mostraron un decremento de la concentración de DA en el estriado, no observándose este deterioro en los tratados además con cocaína. Por otra parte, mediante el condicionamiento de la preferencia de lugar (CPL) confirmamos que la MDMA posee efectos reforzantes y que esta sustancia es capaz de reinstaurar la preferencia de lugar una vez que esta se ha extinguido. La expresión y la reinstauración del CPL inducido por la MDMA dependen de la pauta de condicionamiento que condiciona los efectos neurotóxicos producidos por esta droga. Para finalizar, el tratamiento con MDMA sola o en combinación con cocaína durante la adolescencia favorece los efectos reforzantes de la MDMA durante el periodo adulto. Además, la exposición previa a la cocaína aumenta el tiempo necesario para extinguir la preferencia de lugar inducida por la MDMA.3,4-methylene-dioxy-methamphetamine (MDMA), commonly known as ecstasy, is an illicit recreational drug consumed by teenagers and young adults. The poly-drug pattern is the most common among those observed in MDMA users, with cocaine being a frequently associated drug. The aim of the present study was to evaluate the short- and long-term effects of exposure to MDMA (5, 10, or 20 mg/kg), alone or plus cocaine (25 mg/kg), on adolescent mice. In the acute phase, both drugs produced hyperactivity whether administered alone or concurrently. The highest MDMA dose decreased social contacts and affected the passive avoidance task. However, an anxiolytic effect, studied by means of the elevated plus maze and expressed as an increase in the time spent on the open arms, was observed only in animals treated with both cocaine and MDMA. Neurochemical analyses revealed an increase in striatal DA turnover and a decrease in serotonin cortical turnover in mice treated with MDMA plus cocaine. The studies conducted to establish long-term effects, which were performed 3 weeks after a 3-day treatment of two daily injections of MDMA alone or plus cocaine (6 administrations) during the adolescent period, showed that mice treated with MDMA alone and plus cocaine spent more time engaged in social contact, although those also treated with cocaine exhibited threat behaviors. Furthermore, we observed a neurotoxic effect in mice exposed to 20 mg/kg of MDMA, evident in a decrease in DA levels in the striatum, but this effect was not detected in mice additionally treated with cocaine. On the other hand, using the conditioned place preference (CPP), we have confirmed the rewarding effects of MDMA. In addition, we also show that MDMA can produce reinstatement of place preference after the extinction of this response. The expression and reinstatement of MDMA-induced CPP depend on the conditioning protocol, which conditions the neurotoxic effects produced by this drug. Finally, exposure during adolescence to MDMA alone or plus cocaine facilitates the rewarding effects of MDMA in adulthood. Moreover, previous experience of cocaine increases the time required to extinguish the MDMA-induced CPP

Aporte de la universalización al logro de la equidad en salud

A partir de la definición de equidad, explicada por diferentes autores durante las últimas dos décadas, y la revisión de varias publicaciones que examinan los diferentes enfoques de pensamiento, y que tienen por objeto analizar la equidad en términos de igualdad, justicia, distribución de recursos, prestación de servicios y del manejo del riesgo, se presenta en este artículo una caracterización de dichos enfoques. También se evidencia que la implementación de políticas de universalización en los programas de salud ha sido una estrategia para el logro de la equidad, visto desde los planteamientos liberales como aumento de cobertura en la afiliación, y desde la óptica igualitarista como universalización en el acceso. Las reformas de salud basadas en estos enfoques de equidad aún no logran la igualdad porque mantienen la segregación y permiten diferentes tipos de servicios a diversos grupos poblacionales que distan de ser sistemas verdaderamente universales y equitativos. El propósito de la revisión es dilucidar la relación entre los principios de universalización y equidad para entender la aplicación de ambos principios en el sistema de salud en Colombia.This article presents a characterization of the different approaches to the analysis of equity in terms of equality, justice, distribution of resources, provision of services and risk management, based on the definition provided by different authors in the past two decades on this topic. It is also evident that the implementation of niversalization policies in health programs has been a strategy for achieving equity, grounded on liberal approaches such as increased coverage, and egalitarian perspectives such as the universalization of access. Health reforms based on these equity approaches havenot been enough to achieve equality yet because they maintain segregation and allow different types of services to different population groups, which is far from being a truly universal and equitable system. The purpose of this review is to elucidate the relationship between the principles of universalization and equity to understand the application of both principles in the health system of Colombia

Effect of the CB1 cannabinoid agonist WIN 55212-2 on the acquisition and reinstatement of MDMA-induced conditioned place preference in mice

<p>Abstract</p> <p>Background</p> <p>Numerous reports indicate that MDMA users consume other psychoactive drugs, among which cannabis is one of the most common. The aim of the present study was to evaluate, using the conditioned place preference, the effect of the cannabinoid agonist WIN 55,212-2 on the rewarding effects of MDMA in mice.</p> <p>Methods</p> <p>In the first experiment adolescent mice were initially conditioned with 1.25, 2.5 or 5 mg/kg of MDMA or 0.1 or 0.5 mg/kg of WIN and subsequently with both drugs. Reinstatement of the extinguished preference by priming doses was performed in the groups that showed CPP. In the second experiment, animals were conditioned with 2.5 or 5 mg/kg of MDMA and, after extinction, reinstatement of the preference was induced by 0.5 or 0.1 mg/kg of WIN.</p> <p>Results</p> <p>A low dose of WIN 55212-2 (0.1 mg/kg) increased the rewarding effects of low doses of MDMA (1.25 mg/kg), although a decrease in the preference induced by MDMA (5 and 2.5 mg/kg) was observed when the dose of WIN 55212-2 was raised (0.5 mg/kg). The CB1 antagonist SR 141716 also increased the rewarding effects of the lowest MDMA dose and did not block the effects of WIN. Animals treated with the highest WIN dose plus a non-neurotoxic dose of MDMA exhibited decreases of striatal DA and serotonin in the cortex. On the other hand, WIN 55212-2-induced CPP was reinstated by priming injections of MDMA, although WIN did not reinstate the MDMA-induced CPP.</p> <p>Conclusions</p> <p>These results confirm that the cannabinoid system plays a role in the rewarding effects of MDMA and highlights the risks that sporadic drug use can pose in terms of relapse to dependence. Finally, the potential neuroprotective action of cannabinoids is not supported by our data; on the contrary, they are evidence of the potential neurotoxic effect of said drugs when administered with MDMA.</p

Health market failures: Colombian case

Introduction: Major insurance flaws can be found in the delivery of health services, both by the public and the private sector, worldwide. Objective: To review the current status of the health system in Colombia based on the description, organization and analysis of market failures. Materials y methods: A classification of health market failures in Colombia was made based on the information collected through bibliographical references and papers available on economics in Colombia and Latin America in the past two decades. Results: The insurance and health delivery service markets are complex enough as to ensure the perfect competition posed by the neoliberal model. The need for natural monopolies, the problems of asymmetric information for users and providers, the moral risk and evasion in the insurance, the adverse selection made by insurers and providers, and the corruption in the management of public resources are the causes of this behavior. In addition, the current health model fails structurally in three dimensions: 1) the supply and demand for services, 2) the access and quality of services, and 3) the financial sustainability. Conclusion: There are significant failures in the Colombian health market which make the system inefficient and inequitable; this situation demands for reconsideration of an economic model for financing and operation under a new paradigm

Fallas del mercado de salud colombiano

Introducción. En la prestación de servicios de salud, tanto por parte del sector público como el privado, existen importantes fallas en el aseguramiento a nivel mundial.Objetivo. Realizar una revisión del sistema actual de salud en Colombia a partir de la descripción, organización y análisis de las fallas del mercado.Materiales y métodos. Se realizó una clasificación de las fallas del mercado de la salud en Colombia, basada en información recolectada a través de referencias bibliográficas y artículos disponibles en términos económicos para Colombia y Latinoamérica en las últimas dos décadas.Resultados. Los mercados de aseguramiento y prestación de servicios de salud resultan complejos para garantizar la competencia perfecta que plantea el modelo neoliberal. La necesidad de monopolios naturales; los problemas de información asimétrica de los usuarios y los prestadores; el riesgo moral y evasión en el aseguramiento; la selección adversa que hacen aseguradores y prestadores, y la corrupción en el manejo de los recursos públicos son las causas de este comportamiento. Además, el modelo actual de salud falla estructuralmente en tres dimensiones: 1) oferta y demanda de servicios, 2) acceso y calidad de los servicios y 3) sostenibilidad financiera.Conclusión. Existen importantes fallas del mercado de salud en Colombia que hacen ineficiente e inequitativo el sistema y obligan a replantear un modelo económico de financiación y operación bajo un nuevo paradigma.Introduction: Major insurance flaws can be found in the delivery of health services, both by the public and the private sector, worldwide.Objective: To review the current status of the health system in Colombia based on the description, organization and analysis of market failures.Materials y methods: A classification of health market failures in Colombia was made based on the information collected through bibliographical references and papers available on economics in Colombia and Latin America in the past two decades.Results: The insurance and health delivery service markets are complex enough as to ensure the perfect competition posed by the neoliberal model. The need for natural monopolies, the problems of asymmetric information for users and providers, the moral risk and evasion in the insurance, the adverse selection made by insurers and providers, and the corruption in the management of public resources are the causes of this behavior. In addition, the current health model fails structurally in three dimensions: 1) the supply and demand for services, 2) the access and quality of services, and 3) the financial sustainability.Conclusion: There are significant failures in the Colombian health market which make the system inefficient and inequitable; this situation demands for reconsideration of an economic model for financing and operation under a new paradigm

A Methanol Extract of Brugmansia arborea Affects the Reinforcing and Motor Effects of Morphine and Cocaine in Mice

Previous reports have shown that several of the effects of morphine, including the development of tolerance and physical withdrawal symptoms, are reduced by extracts of Brugmansia arborea (L.) Lagerheim (Solanaceae) (B. arborea). In the present study we evaluate the action of the methanol extract of B. arborea (7.5–60 mg/kg) on the motor and reinforcing effects of morphine (20 and 40 mg/kg) and cocaine (25 mg/kg) using the conditioned place preference (CPP) procedure. At the doses employed, B. arborea did not affect motor activity or induce any effect on CPP. The extract partially counteracted morphine-induced motor activity and completely blocked the CPP induced by 20 mg/kg morphine. On the other hand, B. arborea blocked cocaine-induced hyperactivity but did not block cocaine-induced CPP. Reinstatement of extinguished preference with a priming dose of morphine or cocaine was also inhibited by B. arborea. The complex mechanism of action of B. arborea, which affects the dopaminergic and the cholinergic systems, seems to provide a neurobiological substrate for the effects observed. Considered as a whole, these results point to B. arborea as a useful tool for the treatment of morphine or cocaine abuse

Role of the dopaminergic system in the acquisition, expression and reinstatement of MDMA-induced conditioned place preference in adolescent mice.

BACKGROUND: The rewarding effects of 3,4-methylenedioxy-metamphetamine (MDMA) have been demonstrated in conditioned place preference (CPP) procedures, but the involvement of the dopaminergic system in MDMA-induced CPP and reinstatement is poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the effects of the DA D1 antagonist SCH 23390 (0.125 and 0.250 mg/kg), the DA D2 antagonist Haloperidol (0.1 and 0.2 mg/kg), the D2 antagonist Raclopride (0.3 and 0.6 mg/kg) and the dopamine release inhibitor CGS 10746B (3 and 10 mg/kg) on the acquisition, expression and reinstatement of a CPP induced by 10 mg/kg of MDMA were evaluated in adolescent mice. As expected, MDMA significantly increased the time spent in the drug-paired compartment during the post-conditioning (Post-C) test, and a priming dose of 5 mg/kg reinstated the extinguished preference. The higher doses of Haloperidol, Raclopride and CGS 10746B and both doses of SCH 23390 blocked acquisition of the MDMA-induced CPP. However, only Haloperidol blocked expression of the CPP. Reinstatement of the extinguished preference was not affected by any of the drugs studied. Analysis of brain monoamines revealed that the blockade of CPP acquisition was accompanied by an increase in DA concentration in the striatum, with a concomitant decrease in DOPAC and HVA levels. Administration of haloperidol during the Post-C test produced increases in striatal serotonin, DOPAC and HVA concentrations. In mice treated with the higher doses of haloperidol and CGS an increase in SERT concentration in the striatum was detected during acquisition of the CPP, but no changes in DAT were observed. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that, in adolescent mice, the dopaminergic system is involved in the acquisition and expression of MDMA-induced CPP, but not in its reinstatement

The novelty-seeking phenotype modulates the long-lasting effects of intermittent ethanol administration during adolescence.

The aim of the present study was to investigate if a novelty-seeking phenotype mediates the long-lasting consequences of intermittent EtOH intoxication during adolescence. The hole board test was employed to classify adolescent mice as High- or Low-Novelty Seekers. Subsequently, animals were administered ethanol (1.25 or 2.5 g/kg) on two consecutive days at 48-h intervals over a 14-day period. Anxiety levels--measured using the elevated plus maze- spontaneous motor activity and social interaction test were studied 3 weeks later. A different set of mice underwent the same procedure, but received only the 2.5 g/kg dose of ethanol. Three weeks later, in order to induce CPP, the same animals were administered 1 or 6 mg/kg of cocaine or 1 or 2.5 mg/kg MDMA. The results revealed a decrease in aggressive behaviors and an anxiolytic profile in HNS mice and longer latency to explore the novel object by LNS mice. Ethanol exposure enhanced the reinforcing effects of cocaine and MDMA in both groups when CPP was induced with a sub-threshold dose of the drugs. The extinguished cocaine-induced CPP (1 and 6 mg/kg) was reinstated after a priming dose in HNS animals only. Our results confirm that intermittent EtOH administration during adolescence induces long-lasting effects that are manifested in adult life, and that there is an association between these effects and the novelty-seeking phenotype