Extinction of consummatory behavior in rats

Two experiments with rats studied the relationship between reinforcer magnitude and frequency, and extinction rate in a consummatory situation with rats. In Experiment 1, groups received access to either a 2% or a 32% sucrose solution during twenty 5-min sessions and were subsequently shifted to extinction (access to an empty sipper tube). Goal tracking time (time spent near the sipper tube) was the dependent measure. Extinction was faster after training with 2% solution than with 32% solution. In Experiment 2, extinction was faster after training with 50% partial reinforcement than with continuous reinforcement. In both experiments, extinction was gradual and rats exhibited spontaneous recovery of goal-tracking behavior. Results are discussed in the context of evidence pointing to a dissociation of consummatory and instrumental behavior.Fil: Mustaca, Alba Elisabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Freidin, Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Papini, Mauricio Roberto. Texas Christian University; Estados Unido

Consummatory successive negative contrast in young and middle-aged rats

Contraste negative sucesivo consumatorio en ratas jovenes y maduras. Se evaluaron las respuestas de ratas maduras (14 meses) y jóvenes (3 meses) en una situación de contraste sucesivo negativo consumatorio (cSNC). Los animales experimentales tuvieron acceso a una solución azucarada al 32% (Fase de pre-cambio) durante 10 ensayos diarios de 5 min. seguidos de 5 ensayos de acceso a la misma solución con una concentración al 4% (Fase de post-cambio). Los animales del grupo control recibieron la solución al 4% durante los 15 ensayos. El intervalo de retención entre el último día de pre-cambio y el primero de post-cambio fue de a 1 o 5 días. El cSNC fue similar entre las ratas maduras y jóvenes en la condición de un día de retención. En cambio, las ratas maduras se recuperaron más rápido del cSNC cuando el intervalo de retención fue de 5 días. Estos resultados se discuten en relación con los cambios emocionales y mnésicos de las ratas maduras en comparación con las jóvenes.The performance of middle-aged (14-month old) and young (3-month old) rats was assessed in the consummatory successive negative contrast (cSNC) situation. Rats received 10 daily preshift trials of access to a 32% sucrose solution followed by 5 postshift trials of access to 4% sucrose solution. Unshifted controls had access to the 4% solution in every trial. The retention interval between the last preshift trial and the first postshift trial was either 1 day or 5 days in different groups. cSNC was generally similar in middle-age and young rats in the 1-day retention interval condition. However, middle-age rats recovered faster than young rats from cSNC when a 5-day retention interval was used. This finding is discussed in relation to age-related changes in memory and emotion.Fil: Bentosela, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: D'Ambros, Maria de los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Mustaca, Alba Elisabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Papini, Mauricio Roberto. Texas Christian University; Estados Unido

Administration of corticosterone after the first downshift trial enhances consummatory successive negative contrast

Rats given access to a 32% sucrose solution and then downshifted to a 4% solution exhibit less contact with the sipper tube than unshifted controls always given access to 4% solution. This phenomenon, called consummatory successive negative contrast, was facilitated in Experiment 1 by a post-trial injection of corticosterone (3 mg/kg) administered immediately after the first downshift trial. Experiment 2 demonstrated that this facilitatory effect of post-trial corticosterone does not occur when administered 3 hr after the first downshift trial. These results support the hypothesis that corticosterone strengthens an aversive emotional component elicited by the surprising downshift in reward magnitude during the initial downshift trial.Fil: Bentosela, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Universidad de Buenos Aires. Facultad de Psicología; ArgentinaFil: Muzio, Ruben Nestor. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Psicología; ArgentinaFil: Ruetti, Eliana Martha. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Psicología; ArgentinaFil: Mustaca, Alba Elisabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina. Universidad de Buenos Aires. Facultad de Psicología; ArgentinaFil: Papini, Mauricio Roberto. Texas Christian University; Estados Unido

Retenção e extinção diferida de uma resposta instrumental no sapo Rhinella arenarum: efeitos do overtraining

Amphibians and mammals share common basic mechanisms for associative learning. However, it has been observed that certain reinforcement paradigms produce opposite results. For example, increasing the number of reinforced trials during acquisition (Overtraining) improves mammals’ extinction and impairs amphibians’. The present study evaluates in toads, the effect of overtraining on response retention after 8 days without training. Two groups of animals were trained in a runway receiving 5 or 15 acquisition trials respectively. After acquisition ended, each group remained 8 days without training and then received 8 extinction trials. Differences were not observed in the spontaneous decay rate. Since it had previously observed that using the same parameters in the acquisition leads to a faster extinction in the 5 days group, it is consider the idea that mechanisms underlying extinction and spontaneous decay differs.Los anfibios y los mamíferos comparten mecanismos básicos comunes para el aprendizaje asociativo. Sin embargo, se observa que algunos paradigmas de refuerzo producen resultados opuestos. Por ejemplo, el aumento del número de ensayos reforzados durante la adquisición (sobreentrenamiento) acelera la extinción en mamíferos, pero la retarda en anfibios. Este estudio evalúa en sapos los efectos del sobreentrenamiento sobre la retención de una respuesta luego de 8 días sin entrenamiento y la subsecuente extinción diferida. Se entrenaron dos grupos de animales en un corredor recto durante 5 o 15 ensayos de adquisición, un ensayo por día. La adquisición fue seguida por un intervalo de retención de 8 días sin entrenamiento, y luego por 8 ensayos de extinción. No se observaron diferencias en la tasa de decaimiento durante el primer ensayo de extinción oen la tasa de extinción diferida. Dado que los mismos parámetros de entrenamiento habían permitido observar un claro efecto de sobreentrenamiento en la extincióninmediata, se propone que los mecanismos que regulan la extinción instrumental son diferentes de los que actúan en el decaimiento espontáneo de la respuesta.Palabras clave: aprendizaje instrumental, anfibios, sobreentrenamiento, extinción.Os anfíbios e os mamíferos compartilham mecanismos básicos comuns para a aprendizagem associativa. No entanto, observa-se que alguns paradigmas de reforço produzem resultados opostos. Por exemplo, o aumento do número de ensaios reforçados durante a aquisição (overtraining) acelera a extinção em mamíferos, mas a retarda em anfíbios. Este estudo avalia em sapos os efeitos do overtraining sobre a retenção de uma resposta após 8 dias sem treinamento e a subsequente extinção diferida. Treinaram-se dois grupos de animais em umcorredor reto durante 5 ou 15 ensaios de aquisição, um ensaio por dia. A aquisição foi seguida por um intervalo de retenção de 8 dias sem treinamento, e depois por 8  ensaios de extinção. Não se observaram diferenças na taxa de decaimento durante o primeiro ensaio de extinção ou na taxa de extinção diferida. Devido a que os mesmos parâmetros de treinamento tinham permitido observar um claro efeito de overtraining na extinção imediata, se propõe que os mecanismos que regulam a extinção instrumental são  diferentes dos que atuam no decaimento espontâneo da resposta.Palavras-chave: aprendizagem instrumental, anfibios, overtraining, extinção

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Colamus humanitatem: Nurturing human nature

En un ensayo sobre la ira, el antiguo filósofo Séneca advierte lo inútil que es albergar emociones negativas, dada la inminencia de la muerte, condición que, en últimas, nos hace iguales como humanos. Los antiguos filósofos, creían que las emociones estaban basadas en cogniciones y que por eso eran modificables a través de ejercicios espirituales. Las investigaciones actuales demuestran que los aspectos cognitivos y emocionales de la  sicología humana son maleables (crianza), pero que también requieren expresión genética (naturaleza). Un paralelo entre el comportamiento individual y las fuerzas sociopolíticas sugiere un marco para la crisis ambiental actual, otro “ecualizador” humano. Dos preguntas críticas surgen: ¿Es suficiente la experiencia acumulada de los dos últimos siglos para conseguir medidas correctivas que puedan impedir la degradación ambiental? o ¿es necesario que ocurra un evento catastrófico de degradación ambiental significativa a largo plazo para que las medidas correctivas puedan alcanzar consenso en el nivel socio-político?In an essay on anger, the ancient philosopher Seneca warns of the futility of harboring negative emotions given the imminence of death—the ultimate human equalizer. Ancient philosophers like Seneca believed that emotions are based on cognitions (beliefs) and are therefore modifiable through spiritual exercises. Modern research shows that the emotional and cognitive aspects of human psychology are malleable (nurture), but also require gene expression (nature). A parallel between individual behavior and socio-political forces suggests a framework for the current environmental crisis— another human equalizer. Two critical questions are suggested: Is the amassed experience of the last few centuries sufficient to lead to corrective measures that would avoid environmental degradation? Or would a catastrophic event with significant longterm environmental degradation have to occur before corrective measures reach consensus at the socio-political level?

Scaling relative incentive value in anticipatory behavior

Papini and Pellegrini (Papini, M. R., & Pellegrini, S. Scaling relative incentive value in consummatory behavior. Learning and Motivation, in press) observed that, within limits, the level of consummatory responding of rats exposed to incentive downshifts in the concentration of sucrose solutions was similar when the ratio of test/training solutions was the same. For example,32 fi 4% and 16 fi 2% downshifts (1:8 test/training ratios) lead to similar levels of consummatorybehavior, despite differences in the absolute concentrations of the solutions involved in the downshift. This suggests the applicability of Weber’s law to spaced-trial, incentive-downshift situations. Experiment 1 extended these results to runway performance using food pellets as reward, and Experiment 2 to lever pressing performance, using an autoshaping procedure and sucrose solutions as rewards. The results conform well to the test/training ratio suggesting that Weber’s law is applicable to anticipatory behavior. A simple mathematical rule that can be easily incorporated into models based on linear operators describes the results of consummatory and anticipatory behavior experiments.Fil: Pellegrini, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Papini, Mauricio Roberto. Texas Christian University; Estados Unido

Scaling relative incentive value in consummatory behavior

Surprising downshifts from more preferred (training incentive) to less preferred incentives (test incentive) are usually accompanied by emotional activation and suppression of conditioned behavior in rats. Two experiments were designed to determine whether consummatory behavior is similarly affected by downshifts of equal proportions. Within limits, the degree of consummatory responding during incentive downshift was similar with equal ratios of test concentration to training concentration. Thus, 32% to 4% and 16% to 2% downshifts (1:8 test/training ratios) caused similar levels of consummatory behavior, despite differences in the absolute concentrations of the solutions involved in the downshift. An interpretation based on sensory contrast was discarded because of the long intervals between training and test solutions (40 min and 24 h in Experiments 1 and 2, respectively). It is suggested that Weber’s law regulates behavioral suppression after reward downshifts. A theoretical framework for the interpretation of these data is presented.Fil: Papini, Mauricio Roberto. Texas Christian University; Estados UnidosFil: Pellegrini, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin

Evolución biológica: traducción de Florencia Daneri y Rubén Muzio

La evolución puede ser definida como un fenómeno que resulta de la interacción de procesos evolutivos, tales como selección natural y deriva génica, y patrones evolutivos, tales como las restricciones impuestas por la historia filogenética. Los procesos pueden ser vistos como “fuerzas innovadoras” que ocasionan novedad y cambio, mientras que los patrones filogenéticos como “fuerzas conservadoras” que proveen el material crudo para el cambio. Por ejemplo, en la evolución de los vertebrados terrestres, incluyendo anfibios, reptiles, aves y mamíferos, una variedad impresionante de formas ha evolucionado, adaptándose a vivir bajo un amplio rango de condiciones ambientales.Fil: Papini, Mauricio Roberto. Texas Christian University; Estados UnidosFil: Daneri, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Muzio, Ruben Nestor. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin