Resveratrol inhibits nicotine-induced conditioned place preference in mice

Abstract Nicotine addiction leads to in a huge burden on public health and the economy worldwide. Resveratrol (3,5,4'-tetrahydroxystilbene) is the most well-known polyphenolic stilbenoid. Resveratrol was shown to exhibit positive effects on numerous mechanisms that are important for drug and substance addiction. Thus, this study aimed to examine the effect of resveratrol on nicotine addiction. Intraperitoneal (i.p.) treatment with nicotine (0.5 mg/kg) significantly enhanced time spent in the nicotine-paired compartment. Resveratrol (50 and 75 mg/kg, i.p.) and varenicline (2 mg/kg, i.p.) co-administered with nicotine during the 3-day conditioning period effectively diminished the acquisition of nicotine-induced conditioned place preference (CPP). On the other hand, the administration of resveratrol (50 and 75 mg/kg, i.p.) and varenicline (2 mg/kg, i.p.) decreased the low dose (0.1 mg/kg, i.p.) nicotine-induced reinstatement. The results suggest that resveratrol and varenicline inhibit the acquisition and reinstatement of nicotine's reward properties. Resveratrol displayed similar results in the CPP phases as obtained with the reference drug varenicline. In conclusion, resveratrol could be beneficial as an adjuvant pharmacotherapy for nicotine addiction; however, more investigation is needed to completely explain this property.

Recaída de Variabilidade Operante com a Combinação dos Procedimentos de Renovação, Restabelecimento e Ressurgência / Relapse of Operant Variability with the Combination of the Renewal, Reinstatement, and Resurgence Procedures

Resumo O reaparecimento de variabilidade comportamental previamente extinta (i.e., recaída) foi investigado por meio dos modelos experimentais de renovação, restabelecimento e ressurgência. Na Fase de Treino (contexto A), ao serem expostos ao esquema múltiplo Lag 10 Acoplado, ratos apresentaram níveis similares de variabilidade nos dois componentes. Na Fase de Eliminação (contexto B), o esquema múltiplo Repetição Repetição promoveu a extinção da variabilidade. Na Fase de Teste (contexto A), com a suspensão da contingência de repetição e a liberação de reforços independentes, a variabilidade reapareceu no componente "Lag 10", anteriormente correlacionado com reforçamento da variação, mas não no componente "Acoplado". Esse resultado sugere que a variabilidade observada no teste de recaída corresponde à variabilidade operante, e não à variabilidade induzida pela extinção.

Abstract The reappearance of previously extinguished behavioral variability (i.e. relapse) was investigated with three experimental models: renewal, reinstatement and resurgence. In the Training Phase (context A), when exposed to the multiple Lag 10 Yoke schedule, rats showed similar levels of variability in both components. In the Elimination Phase (context B), the multiple Repetition schedule promoted the extinction of variability. In the Test Phase (context A), with the suspension of the repetition contingency and the delivery of response-independent reinforcers, variability reappeared in the "Lag 10" component, the one previously correlated with the reinforcement of variation, but not in the "Yoke" component. This result suggests that the variability observed in the relapse test corresponded to operant variability, and not to extinction-induced variability.

Effect of different extinction methods on morphine-induced conditioned place preference in mouse / 国际药学研究杂志

Objective To compare the effect of extinction using different methods and the subsequent reinstatement of morphine-primed on morphine-induced conditioned place preference (CPP).

Effect of different extinction methods on morphine-induced conditioned place preference in mouse / 国际药学研究杂志

Objective To compare the effect of extinction using different methods and the subsequent reinstatement of morphine-primed on morphine-induced conditioned place preference (CPP). Methods Mouse received morphine(10 mg/kg, sc) or saline (10 mg/kg, sc) injections alternately for 8 days to establish CPP. Different methods were used for extinction. Program 1, withdrawal group. Extinction sessions were conducted 21 days after the CPP test at 7 days interval; Program 2, extinction test group. Extinction sessions were carried out once a day from the second day after the CPP test; Program 3, extinction training group. Extinction sessions began one day after the CPP test. Mice were treated alternately two trials daily, in compartments where they received saline instead of morphine. A test for reinstatement was performed on the 2nd or 7th day after all groups completed extinction by 5 mg/kg morphine-primed. Results Morphine injections induce strong CPP. In withdrawal group, CPP extinguished on the 35th day and maintained for at least 28 days. Six trials extinction tests and 4 trials extinction training caused morphine induced CPP extinction. The three programs mentioned above were all primed by 5mg/kg morphine. Conclusion Morphine induced mouse CPP model can maintain at least 28 days, both extinction test and training can accelerate the extinction of CPP, and reinstatement by 5 mg/kg morphine.

Comparative proteomic analysis of the nucleus accumbens during extinction and reinstatement of morphine dependence / Análisis proteómico comparativo del núcleo accumbens durante laextinción y recaída de la dependencia a la morfina

BACKGROUND: The aim of this study was to detect differentially expressed proteins in the nucleus accumbens between the states of extinction and reinstatement of morphine addiction. Numerous studies on the neurobiological mechanisms concerning drug craving and relapse have been reported to date, but data on their relationship with the underlying key molecular mechanisms involved remain limited. METHODS: In this study, 40 male SpragueDawley rats were equally randomized into a saline group and a morphine group. Both groups received drug selfadministration training, after which extinction models were established naturally. The groups were further divided into two subgroups for extinction and reinstatement tests. Cerebral nucleus accumbens masses were measured for total protein extraction. Twodimensional electrophoresis was performed to determine differential protein spots. These differential proteins were then enzymolysed and identified using mass spectrography. RESULTS: The proteins were classified as fatty acidbinding protein, serine/threonine protein phosphatase 2A catalytic subunit beta isoform, serine/threonine protein phosphatase 2A catalytic subunit alpha isoform, serine/threonine protein phosphatase 2A regulatory subunit B² subunit gamma or heat shock protein 90 cochaperone CDC37. CONCLUSION: Significant changes in five proteins were detected between extinction and reinstatement. These proteins are correlated with phosphorylation and the tricarboxylic acid cycle.

ANTECEDENTES: El objetivo de este estudio fue detectar las proteínas diferencialmente expresadas en el núcleo accumbens entre los estados de extinción y recaída de la adicción a la morfina. Hasta la fecha se han reportado numerosos estudios en relación con los mecanismos neurobiológicos del deseo incontenible y recaída en el consumo de drogas, pero los datos sobre su relación con los mecanismos moleculares fundamentales subyacentes implicados, siguen siendo limitados. MÉTODO: En este estudio, 40 ratas machos SpragueDawley fueron por igual asignadas de manera aleatoria a un grupo salino y un grupo de morfina. Ambos grupos recibieron entrenamiento de autoadministración de drogas, después de lo cual se establecieron modelos de extinción de manera natural. A su vez, los grupos fueron luego subdivididos en dos subgrupos para realizar pruebas de extinción y recaída. Se procedió a medir las masas cerebrales del núcleo accumbens para la extracción total de proteína. Se realizó una electroforesis bidimensional para determinar manchas proteicas diferenciales. Estas proteínas diferenciales fueron entonces sometidas a enzimólisis e identificadas mediante espectrografía de masa. RESULTADOS: Las proteínas fueron clasificadas como proteína de unión a ácidos grasos, isoforma beta de la subunidad catalítica serinatreonina proteína fosfatasa 2A, isoforma alfa de la subunidad catalítica serinatreonina proteína fosfatasa 2A, subunidad gamma subunidad B" de la serinatreonina proteína fosfatasa 2A, o la proteína CDC37 cochaperona 90 de choque térmico. CONCLUSIÓN: Se detectaron cambios significativos en cinco proteínas entre la extinción y la recaída. Estas proteínas están correlacionadas con la fosforilación y el ciclo del ácido tricarboxílico.

Asociaciones excitatorias entre el contexto y la consecuencia en la reinstalación de respuestas extinguidas en el aprendizaje causal humano / Excitatory context-consequence associations in the reinstatement of extinguished responses in human causal learning

En dos experimentos, estudiantes universitarios aprendieron una relación predictiva entre un evento y una consecuencia, la que posteriormente fue extinguida presentando el evento sin la consecuencia. En el Experimento 1, se presentó la consecuencia por sí sola después de la extinción, ocasionando la reaparición de la relación predictiva aprendida originalmente, asemejándose al fenómeno del condicionamiento Pavloviano conocido como "reinstalación". Este experimento demostró además, que no es necesario apelar a asociaciones inhibitorias para explicar la reinstalación, sino que solamente a asociaciones excitatorias entre el contexto y la consecuencia. El Experimento 2 confirmó la generalidad de estos hallazgos utilizando otro procedimiento de aprendizaje causal. Se discuten estos hallazgos en términos de las diferencias entre el aprendizaje causal y el condicionamiento Pavloviano y de la posible existencia de dos mecanismos alternativos de extinción: desaprendizaje para extinguir asociaciones no consolidadas e inhibición para las consolidadas.

In two experiments, undergraduates learned a predictive relationship between an event and a consequence, which was subsequently extinguished by presenting the event without the consequence. In Experiment 1, participants were exposed to the consequence by itself after extinction, occasioning the reappearance of the originally learned predictive relationship, resembling a phenomenon known as Reinstatement in the field of Pavlovian conditioning. This experiment further demonstrated that reinstatement can be explained without appealing to inhibitory associations, but only by mean of excitatory associations between the context and the consequence. Experiment 2 confirmed the generality of these findings using a different procedure of causal learning. The findings are discussed in terms of differences between Pavlovian conditioning and causal learning and of the possible existence of two mechanisms of extinction: unlearning to extinguish non consolidated associations and inhibition for the consolidated associations.

Integración familiar de jóvenes con discapacidad intelectual moderada, pertenecientes a un hogar de menores / Reinstating youngsters with moderate mental disability from a group home for minors back to their families

El trabajo que se informa presenta una descripción y evaluación de un estudio de casos de reintegración familiar de tres jóvenes con discapacidad intelectual moderada pertenecientes a un hogar de menores, desarrollado durante tres años. La metodología utilizada estuvo centrada principalmente en el enfoque biográfico, con la técnica de relatos de vida. Además de presentar las características de sus familias, específicamente de sus madres, los resultados aportan antecedentes claves para poder potenciar el sistema de integración familiar actual que existe para la atención de niños, niñas y jóvenes con necesidades educativas especiales. De los tres casos, sólo uno concretó la reintegración familiar de la joven discapacitada, el segundo está en proceso de finalizar la integración y en el tercero, la madre desertó. Se observa que es compleja la integración en las familias de los menores que asisten a centros de protección. Como factores claves para el éxito de la intervención, se reconocen las redes de apoyo sociales y familiares, las estrategias individuales para revincularse con la hija y resignificar su discapacidad, el apoyo de la institución y el trabajo multidisciplinario. Finalmente se concluye a partir de estos casos, cuáles serían los aspectos esenciales que permiten realmente que los menores crezcan y vivan en familia como seres íntegros y plenos. Para ello se requiere contar con un plan de intervención y un seguimiento constante del proceso, en el que se trabaje no sólo con la madre o tutor principal del menor, sino que también se incorpore a toda la familia en el proceso.

The article presents a description and evaluation of a three year case study of three youngsters with moderate mental disability from a group home for minors. We used a biography approach, and a life story technique. Through this technique, the person articulates his or her past, present and future in an interview or an open interaction. Our goal was to understand and face the mothers' life experiences in order to create an intervention method based on their own reality and perspective. Apart from presenting the children's family characteristics, particularly that of their mothers, the results bring out key information that strengthen and promote the current system of family integration for children and youngsters with special educational needs. Out of the three cases, only one family achieved the reinstatement of their child with a disability; the second family is in the process of finishing the reinstatement, and in a third case, the mother abandoned the process. Based on these experiences, reinstating a child who was looked after by a child care and protection center back to his or her family, is a complex issue. The family plays a fundamental role in the process of bringing their child back into their homes, and is a key factor for a successful intervention. Families who have a support network, both at an individual and social level, have better possibilities of reinstating their child back into the family. Another important point to consider is individual strategies mothers use to renew the bond with their child, which are influenced by the stages they are going through regarding the adaptation process and acceptance of the disability. Other aspects that influence whether families abandon the reinstatement process or not are the type of disability, the cause of transfer to the care and protection center, the stage that each mother is going through regarding their child's disability linked to their vital cycle, the mothers' age and their constant denial in coping with disability and their maternal roles. The family reinstatement program is recognized as a good system which allows children with disabilities to achieve better growth and development with their families, while acknowledging at the same time, that adoption is practically nonexistent. This system requires constant interventions and follow-ups, not only with the tutor, but also including the whole family in the process. Moreover, multi-disciplinary work at home, in community institutions and in other social levels that bring support to the family's readjustment of their internal bonds and structure, should be considered key interventions. Strengthening parental figures helps parents change their perspective regarding their child's disability, and is crucial in accomplishing true social integration, as well as allowing children to grow and live in a family as wholesome and complete beings.