Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Hemizygous Le-Cre Transgenic Mice Have Severe Eye Abnormalities on Some Genetic Backgrounds in the Absence of LoxP Sites

Eye phenotypes were investigated in Le-Cre(Tg/-); Pax6(fl/+) mice, which were expected to show tissue-specific reduction of Pax6 in surface ectoderm derivatives. To provide a better comparison with our previous studies of Pax6(+/-) eye phenotypes, hemizygous Le-Cre(Tg/-) and heterozygous Pax6(fl/+)mice were crossed onto the CBA/Ca genetic background. After the Le-Cre transgene had been backcrossed to CBA/Ca for seven generations, significant eye abnormalities occurred in some hemizygous Le-Cre(Tg/-); Pax6(+/+) controls (without a floxed Pax6(fl) allele) as well as experimental Le-Cre(Tg/-); Pax6(fl/+) mice. However, no abnormalities were seen in Le-Cre(-/-); Pax6(fl/+) or Le-Cre(-/-); Pax6(+/+) controls (without the Le-Cre transgene). The severity and frequency of the eye abnormalities in Le-Cre(Tg/-); Pax6(+/+) control mice diminished after backcrossing Le-Cre(Tg/-) mice to the original FVB/N strain for two generations, showing that the effect was reversible. This genetic background effect suggests that the eye abnormalities are a consequence of an interaction between the Le-Cre transgene and alleles of unknown modifier genes present in certain genetic backgrounds. The abnormalities were also ameliorated by introducing additional Pax6 gene copies on a CBA/Ca background, suggesting involvement of Pax6 depletion in Le-Cre(Tg/-); Pax6(+/+) mice rather than direct action of Cre recombinase on cryptic pseudo-loxP sites. One possibility is that expression of Cre recombinase from the Pax6-Le regulatory sequences in the Le-Cre transgene depletes cofactors required for endogenous Pax6 gene expression. Our observation that eye abnormalities can occur in hemizygous Le-Cre(Tg/-); Pax6(+/+) mice, in the absence of a floxed allele, demonstrates the importance of including all the relevant genetic controls in Cre-loxP experiments

Mejora de los conocimientos, procedimientos y actitudes del alumnado de secundaria tras un programa de intervención en educación física para la salud

La scarce amount of works in Spain about the promotion of healthy physical education in teenagers from the educational scope provoked an intervention program, from Physical Education, to improve the conceptual, procedural and attitudinal scopes in secondary students. The intervention program (with the duration of a term) was characterised mainly by the use of a methodology in which the implication of the students, in an active and eminently reflexive way, had priority in class, under an integrative view of P.E. curriculum. In order to do so, the teaching performance made use of a series of resources such as the use of leaflets, a logbook (diary�]like) or the creation of forums by means of e�]mail groups in Internet. The results of the investigation reveal a highly meaningful increase (p.0.001), in the experimental group, in the conceptual, procedural and attitudinal sections of the curriculum around the practice of health�]related physical activity, with regard to a control group. Therefore, it can be concluded highlighting the suitability of the intervention program designed to the improvement of learning in every one of the mentioned scopes in secondary students.La escasez de trabajos en Espana sobre la promocion de actividad fisica saludable en adolescentes, desde el ambito educativo, propicio un programa de intervencion desde la E.F. para mejorar en el alumnado de E.S.O. los ambitos conceptual, procedimental y actitudinal. El programa de intervencion (con una duracion de un trimestre) se caracterizo principalmente por la utilizacion de una metodologia en la que primo la implicacion de los alumnos en las clases de una forma activa y eminentemente reflexiva, bajo una perspectiva integradora del curriculum de E.F. Para ello, la actuacion docente se valio de una serie de recursos didacticos tales como el uso de tripticos, un cuaderno de bitacora (a modo de diario) o la creacion de foros de debate mediante grupos de correo electronico en Internet. Los resultados de la investigacion revelan un aumento altamente significativo (p. 0.001), en el grupo experimental, en los apartados conceptual, procedimental y actitudinal del curriculum en torno a la practica de actividad fisica relacionada con la salud, con respecto a un grupo control. Por tanto, se puede concluir destacando la idoneidad del programa de intervencion disenado para la mejora del aprendizaje en cada uno de los ambitos mencionados en alumnos de secundaria

Depressive symptoms and perception of quality of life in Parkinson's disease Sintomas depressivos e percepção da qualidade de vida na doença de Parkinson

BACKGROUND: Depression has been proposed as a major contributor to poor quality of life (QoL) in Parkinson's disease (PD). OBJECTIVE: To evaluate the relationship between depressive symptoms and QoL in subjects with PD. METHOD: Beck Depression Inventary (BDI) was used to evaluate depressive symptoms and Parkinson's Disease Quality of Life Questionnaire (PDQ-39) to assess the perception of the QoL. RESULTS: Thirty seven patients (19 male/ 18 female) with a typical onset PD and mean disease duration of 7.7 years were studied. Higher scores on BDI correlated with poorer perception of the QoL. This association occurred at the expense of the following PDQ39 domains: mobility, activities of daily living, social support, cognition and emotional well-being dimensions. PD severity also correlated with QoL. CONCLUSION: Our study corroborates the assumption that depressive symptoms contributed significantly to QoL in PD.<br>Introdução: Depressão tem sido proposta como um importante fator para a piora da qualidade de vida (QV) na doença de Parkinson (DP). OBJETIVO: Avaliar a relação entre sintomas depressivos e a QV em indivíduos com DP. MÉTODO: Foi utilizado o Inventário de Depressão de Beck (IDB) para avaliar depressão e o Questionário de Qualidade de Vida na Doença de Parkinson (PDQ-39) para investigar a percepção da QV. RESULTADOS: Trinta e sete pacientes (19 homens e 18 mulheres) com idade de início típica da DP e duração média da doença de 7,7 anos foram estudados. Maiores escores no IDB correlacionaram-se com pior percepção da QV. Essa associação ocorreu em virtude da pior percepção das dimensões de mobilidade, atividades da vida diária, apoio social, cognição e bem-estar emocional do PDQ-39. A gravidade da DP também se correlacionou com a QV. CONCLUSÃO: Nosso estudo corrobora o conceito de que os sintomas depressivos contribuem significativamente para a QV em indivíduos com DP