El Enriquecimiento ambiental en ratas : efectos diferenciales en función del sexo /

Consultable des del TDXTítol obtingut de la portada digitalitzadaEl tratamiento de Enriquecimiento Ambiental (EA) incrementa la estimulación y proporciona oportunidades más ricas y variadas de interacción con el entorno social y físico y ha demostrado ejercer una gran variedad de efectos a largo plazo a nivel neuroanatómico, neuroquímico y conductual en varias especies animales. El EA aumenta el tamaño de la corteza cerebral, incrementa las ramificaciones dendríticas y la neurogénesis hipocampal y mejora las capacidades cognitivas en una variedad de tareas. No obstante, aunque algunas investigaciones han descrito efectos diferenciales del EA en función del sexo, la gran mayoría de estudios que han evaluado los efectos del EA se han realizado con sujetos macho. Además, en humanos existen importantes diferencias de sexo en un gran número de psicopatologías, como la depresión, la esquizofrenia o la adicción a drogas, lo cual evidencia la necesidad de incluir a las hembras en los diseños experimentales. La presente tesis se propone estudiar los efectos del EA en ratas Sprague-Dawley de ambos sexos en pruebas que evalúan exploración y memoria social, reactividad emocional, mecanismos atencionales, aprendizaje y adicción a drogas a lo largo de dos bloques experimentales. El tratamiento se inició después del destete colocando a los animales en grupos de 9-12 individuos en jaulas de enriquecimiento durante 8 o 12 semanas, donde se cambiaban la configuración espacial y los objetos. Las ratas control se estabularon en grupos (2-3 individuos) en jaulas estándar. En el primer bloque experimental se realizaron dos estudios con el propósito de evaluar los efectos del EA en exploración social mediante la prueba de Discriminación Social; en reactividad emocional, mediante el Laberinto elevado en cruz, la respuesta de sobresalto ante un estímulo acústico y la respuesta del eje Hipotálamo-Pituitario-Adrenal en condiciones basales y en respuesta a la exposición a la prueba de la Tabla de agujeros; en mecanismos atencionales, mediante el paradigma de inhibición prepulso; y en aprendizaje espacial, mediante el laberinto Hebb-Williams. Los resultados de este primer bloque mostraron que el EA disminuyó la emotividad en machos y hembras como se observó por la mayor conducta en los brazos abiertos del laberinto elevado en cruz, la mayor exploración en la tabla de agujeros y la menor reactividad del eje HPA en comparación con los animales control. De manera inesperada, el EA disminuyó el porcentaje de inhibición prepulso en machos y hembras, resultado que contrastó con el efecto de mejora en la ejecución del laberinto Hebb-Williams que produjo el tratamiento en los mismos sujetos experimentales. En las pruebas de exploración y reconocimiento social, el EA mostró un efecto diferencial en función del sexo ya que aumentó la exploración y el reconocimiento social en los machos pero los disminuyó en las hembras. El segundo bloque experimental constituyó el tercer estudio, donde se evaluaron los efectos del EA en el consumo de cocaína mediante el paradigma de autoadministración intravenosa. Los resultados mostraron efectos de sexo y de tratamiento, de forma que las hembras se autoadministraron más cocaína que los machos, y el EA aumentó la autoadministración en machos y hembras de forma diferencial. Así, el EA afectó predominantemente a las hembras, quienes aumentaron la conducta de búsqueda de cocaína realizando un número mayor de respuestas en la palanca asociada a la droga. En conjunto, los resultados del presente trabajo indican que el tratamiento de EA produce efectos diferenciales en machos y hembras en función de las tareas evaluadas.Environmental Enrichment (EE) increases stimulation and provides richer sensory, cognitive and motor stimulation through the interaction with the social and fisical environment and produces a wide range of neuroanatomical, neurochemical and behavioral effects in several animal species. Various studies have shown that EE increases brain weight and thickness, dendritic branching and length and also increases hippocampal neurogenesis and survival of newly generated neurons. With regard to cognitive function, it has been consistently shown that EE improved spatial learning in several tasks. But the results obtained from the experiments measuring the effects of EE treatment have been done mainly with male rats, though some results clearly showed sex differences in response to EE. Furthermore, a surge of findings from animals and humans have shown sex differences in several psychopathologies, as depression, esquizofrenia and drug addiction. The aim of the present thesis was to study sex differential effects of EE in Sprague-Dawley rats in tasks that measure social exploration and memory, emotional reactivity, sensoriomotor gating, spatial learning and drug addiction. The work has been divided in 2 experimental blocks: after weaning, rats were housed in groups of 9 -12 in enriched cages during 8 or 12 weeks, were the spatial configuration and objects were changed frequently. Control rats were housed in groups (2-3 animals) in standard cages. In the first experimental work we did two studies, where we studied social exploration in the Social discrimination test; emotional reactivity in the Elevated plus maze, Acoustic startle response and responsiveness of the hypothalamic-pituitay-adrenal (HPA) axis in response to the Hole board test; we measured attentional mechanisms through the prepulse inhibition paradigm; and spatial learning in the Hebb-Williams maze. The main results indicated that enriched animals appeared less emotional since they increase open arm activity, they showed more exploratory behavior in the hole board and less HPA reactivity than controls. EE showed a significant reduction of prepulse inhibition compared to control rats, in contrast with the improvement showed by the enriched rats in the Hebb-Williams maze. Furthermore, the EE effects in the patterns of social investigation were sex dependent, and EE treatment increased exploratory behavior and social discrimination in males and decreased social discrimination in females. In the second experimental block we performed the third study, where we evaluated the effects of EE on cocaine consumption by means of the intravenous self-administration paradigm. The results showed sex and treatment effects, females were more sensitivity to cocaine as shown by the greater amount of cocaine intake. EE increased self- administration in both male and female rats, but females were more affected than males as showed by the higher levels of infusions and the increase in the responses in the active lever. The results of the present thesis indicate that EE treatment produce differential effects in male and female rats in a task dependent manner

Les persones impulsives podrien ser més propenses a desenvolupar addiccions

Un estudi, fet públic per la revista Science, mostra que les rates més impulsives tenen un nombre menor de receptors de dopamina D2/3 al nucli accumbens, una regió del cervell relacionada amb el plaer, i són més propenses a desenvolupar addiccions. Aquesta recerca obre una via per predir la vulnerabilitat addictiva en les persones que tenen una alta impulsivitat. Yolanda Peña, investigadora de la Unitat de Psicologia Mèdica, del Departament de Psiquiatria i de Medicina Legal de la UAB, ha participat en aquest treball, dut a terme a la Universitat de Cambridge.Un estudio hecho público por la revista Science muestra que las ratasmás impulsivas tienen un número menor de receptores de dopaminaD2/3 en el núcleo accumbens, una región del cerebro relacionada con elplacer, y son más propensas a desarrollar adicciones. Esta investigaciónabre una vía para predecir la vulnerabilidad adictiva en las personas quetienen una alta impulsividad. Yolanda Peña, investigadora de la Unidadde Psicología Médica, del Departamento de Psiquiatría y Medicina Legalde la UAB, ha participado en este trabajo, llevado a cabo en laUniversidad de Cambridge

Alcohol-Preferring Rats Show Goal Oriented Behaviour to Food Incentives but Are Neither Sign-Trackers Nor Impulsive.

Drug addiction is often associated with impulsivity and altered behavioural responses to both primary and conditioned rewards. Here we investigated whether selectively bred alcohol-preferring (P) and alcohol-nonpreferring (NP) rats show differential levels of impulsivity and conditioned behavioural responses to food incentives. P and NP rats were assessed for impulsivity in the 5-choice serial reaction time task (5-CSRTT), a widely used translational task in humans and other animals, as well as Pavlovian conditioned approach to measure sign- and goal-tracking behaviour. Drug-naïve P and NP rats showed similar levels of impulsivity on the 5-CSRTT, assessed by the number of premature, anticipatory responses, even when the waiting interval to respond was increased. However, unlike NP rats, P rats were faster to enter the food magazine and spent more time in this area. In addition, P rats showed higher levels of goal-tracking responses than NP rats, as measured by the number of magazine nose-pokes during the presentation of a food conditioned stimulus. By contrast, NP showed higher levels of sign-tracking behaviour than P rats. Following a 4-week exposure to intermittent alcohol we confirmed that P rats had a marked preference for, and consumed more alcohol than, NP rats, but were not more impulsive when re-tested in the 5-CSRTT. These findings indicate that high alcohol preferring and drinking P rats are neither intrinsically impulsive nor do they exhibit impulsivity after exposure to alcohol. However, P rats do show increased goal-directed behaviour to food incentives and this may be associated with their strong preference for alcohol.There are errors in the Funding section. The correct funding information is as follows: The present study was funded by the Wellcome Trust and the Medical Research Council Programme (MRC Ref: G1002231 awarded to BJE, JWD, TWR, Wellcome Trust Ref: 093875/Z/10/Z), and the R24 Alcohol Research Resource Award grant (R24 AA015512) from NIAAA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version of the article. It first appeared from PLoS via http://dx.doi.org/10.1371/journal.pone.013101

Evidence for a Long-Lasting Compulsive Alcohol Seeking Phenotype in Rats

Excessive drinking to intoxication is the major behavioral characteristic of those addicted to alcohol but it is not the only one. Indeed, individuals addicted to alcohol also crave alcoholic beverages and spend time and put much effort into compulsively seeking alcohol, before eventually drinking large amounts. Unlike this excessive drinking, for which treatments exist, compulsive alcohol seeking is therefore another key feature of the persistence of alcohol addiction since it leads to relapse and for which there are few effective treatments. Here we provide novel evidence for the existence in rats of an individual vulnerability to switch from controlled to compulsive, punishment-resistant alcohol seeking. Alcohol-preferring rats given access to alcohol under an intermittent 2-bottle choice procedure to establish their alcohol-preferring phenotype were subsequently trained instrumentally to seek and take alcohol on a chained schedule of reinforcement. When stable seeking-taking performance had been established, completion of cycles of seeking responses resulted unpredictably either in punishment (0.45 mA foot-shock) or the opportunity to make a taking response for access to alcohol. Compulsive alcohol seeking, maintained in the face of the risk of punishment, emerged in only a subset of rats with a predisposition to prefer and drink alcohol, and was maintained for almost a year. We show further that a selective and potent μ-opioid receptor antagonist (GSK1521498) reduced both alcohol seeking and alcohol intake in compulsive and non-compulsive rats, indicating its therapeutic potential to promote abstinence and prevent relapse in individuals addicted to alcohol

Performance deficits of NK1 receptor knockout mice in the 5 choice serial reaction time task: effects of d Amphetamine, stress and time of day.

Background The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon. Methods and Results The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning. Conclusion In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

European journalism observatory: An international consolidated platform for training and professional networks in the Faculty of Information Sciences

El objetivo principal de este proyecto Innova-Docenia era ampliar y consolidar una plataforma de formación internacional y consolidada, para alumnos y alumnas de la Facultad de Ciencias de la Información, como parte del European Journalism Observatory (EJO), fundado por el Instituto Reuters de la Universidad de Oxford. Se trataba de afianzar EJO Spain como plataforma de formación y escaparate de las acciones implementadas en España, donde la Universidad Complutense de Madrid se convertía en el socio español principal. El Observatorio Europeo de Periodismo (EJO), una red de instituciones independientes y sin ánimo de lucro del campo de la comunicación de 14 países, tiene como objetivo tender puentes entre la investigación y la práctica del periodismo en Europa y fomentar el profesionalismo y la libertad de prensa. Promueve el diálogo entre investigadores y profesionales de los medios. Acerca los resultados de la investigación a las personas que trabajan en los medios. Su objetivo es mejorar la calidad del periodismo, contribuir a una mejor comprensión de los medios y fomentar la libertad de prensa y la responsabilidad de los medios. Nació en 2004, como una red de varios socios europeos, coordinados por la Universidad de Lugano y la Universidad de Oxford. Fue diseñado para observar las tendencias en el periodismo y en los medios de comunicación, desde una perspectiva ética y deontológica muy amplia. Desde entonces, sus artículos, investigaciones y editoriales son publicados en las distintas páginas web de cada socio: https://es.ejo-online.eu/red-ej

Ethanol effects on impulsivity in two mouse strains: similarities to diazepam and ketamine

Rationale: The effects of ethanol on attention and impulsivity have been contradictory. Objectives: The aim of the present investigation is to study the effects of acute ethanol administration in measures of attention and response control in the five-choice serial reaction time task (5-CSRTT) in two strains of mice, C57BL/6JOlaHsd and CD1.Materials and methods: Mice were trained in the 5-CSRTT and then were injected intraperitoneally (i.p.) with 0, 0.5, 1 and 2 g/kg ethanol before testing under standard parameters and in a long inter-trial interval (ITI) session, which promotes the emergence of premature responses, a measure of poor inhibitory control. To examine if the effects of ethanol in the 5-CSRTT were due to its actions at GABAA receptors or at NMDA receptors, the GABAA receptor agonist diazepam (1 and 2 mg/kg, i.p.) and the non-competitive NMDA antagonist ketamine (10 and 20 mg/kg, i.p.) were tested in long ITI sessions.Results: Ethanol did not affect attention or impulsivity in the standard procedure, but increased premature responding in long ITI sessions. The effects of ethanol were mimicked by diazepam in both strains of mice, whereas ketamine increased premature responding only in the CD1 strain.Conclusions: Ethanol's ability to increase impulsivity in the 5-CSRTT is mediated by both common and different neurotransmitter systems in the two strains of mice and is dependent on the task's parameters. Furthermore, ethanol did not decrease response accuracy, suggesting that attentional mechanisms are preserved after acute ethanol in mice and that the increases in impulsive behaviour are independent of attentional performance

Les persones impulsives podrien ser més propenses a desenvolupar addiccions

Un estudi, fet públic per la revista Science, mostra que les rates més impulsives tenen un nombre menor de receptors de dopamina D2/3 al nucli accumbens, una regió del cervell relacionada amb el plaer, i són més propenses a desenvolupar addiccions. Aquesta recerca obre una via per predir la vulnerabilitat addictiva en les persones que tenen una alta impulsivitat. Yolanda Peña, investigadora de la Unitat de Psicologia Mèdica, del Departament de Psiquiatria i de Medicina Legal de la UAB, ha participat en aquest treball, dut a terme a la Universitat de Cambridge.Un estudio hecho público por la revista Science muestra que las ratasmás impulsivas tienen un número menor de receptores de dopaminaD2/3 en el núcleo accumbens, una región del cerebro relacionada con elplacer, y son más propensas a desarrollar adicciones. Esta investigaciónabre una vía para predecir la vulnerabilidad adictiva en las personas quetienen una alta impulsividad. Yolanda Peña, investigadora de la Unidadde Psicología Médica, del Departamento de Psiquiatría y Medicina Legalde la UAB, ha participado en este trabajo, llevado a cabo en laUniversidad de Cambridge

Negative Urgency Exacerbates Relapse to Cocaine Seeking After Abstinence.

BACKGROUND: The mechanisms through which drug-cue-induced negative affective states are involved in relapse have not been defined. We tested the hypothesis that in individuals having developed a dorsolateral striatum (DLS)-dependent cue-controlled cocaine-seeking habit, the loss of the opportunity to enact the drug-seeking response during abstinence results in an urge to act that exacerbates relapse severity mediated by negative urgency. METHODS: Eighty-seven male Sprague Dawley rats were trained to seek cocaine under the influence of the conditioned reinforcing properties of drug-paired cues or not. We investigated whether the tendency to relapse depended on the aversive state of withdrawal or instead on the loss of opportunity to perform the ingrained drug-seeking response after periods of abstinence. The striatal locus of control over cocaine seeking at baseline and relapse was investigated using in situ hybridization of the cellular activity marker C-fos and assessment of the sensitivity of instrumental drug seeking to dopamine receptor blockade in the dorsomedial striatum-dependent goal-directed and DLS-dependent habit systems. RESULTS: The development of a DLS-dependent cue-controlled cocaine-seeking habit prior to abstinence resulted in a marked increase in drug seeking at relapse, which was not motivated by a cocaine withdrawal state and was no longer dependent on the DLS habit system. Instead, it reflected the emergence of negative urgency caused by the prevention of the performance of the habit during abstinence and underpinned by transient engagement of the goal-directed system. CONCLUSIONS: These results show that ingrained cue-controlled drug-seeking habits increase the pressure to relapse.Leverhulme Trus