Effects of early-life stress followed by access to stevia or sucralose during adolescence on weight gain, glycemia, and anxiety-related behaviors in male and female rats.

Early-life stress and subsequent high-calorie diets during adolescence are known to be risk factors for developing metabolic and psychological disorders. Although non-nutritive sweeteners such as stevia and sucralose have been a useful alternative to reduce sugar consumption, the effects of prolonged consumption of these sweeteners on metabolism and behavior in adolescents remain unclear. Here, we evaluated the effects of early-stress followed by access to stevia or sucralose during adolescence on weight gain, glycemia, and anxiety-related behaviors in male and female rats. During postnatal days (PNDs) 1-21, pups were separated twice a day, for 180 min each time, from their dam nest while non-separated pups served as controls. The pups were weaned, separated by sex and randomly distributed into the stevia, sucralose and water conditions. During PNDs 26-50, two bottles containing water and stevia or sucralose were placed in the animal home-cages, and body weight and blood glucose measures were scored. On PNDs 50 and 51, behavioral measures were obtained in the open-field test. Results showed that male rats consuming stevia reduced body weight gain, blood glucose and increased locomotion. Early-stress led to low blood glucose and alterations in anxiety and locomotion-related behaviors in a sex-dependent manner. Moreover, sucralose access during adolescence reversed the effects of early-stress on anxiety-related behaviors in female rats. The results suggest that the consumption of stevia and sucralose could be an alternative for the replacement of sugar-sweetened beverages, especially in adolescents who have had adverse early-life experiences.

Diazepam Reduces Escape and Increases Closed-Arms Exploration in Gerbils After 5 min in the Elevated Plus-Maze.

Despite the wide implementation of the elevated plus-maze (EPM) test to assess anxiety-related behaviors in rodents, the interpretation of these measures in gerbils has received limited attention. Here, male gerbils were treated with vehicle or diazepam, followed by a 20-min EPM session. EPM data were subjected to minute-by-minute, 5-min bins and factor analyses. During the first 5-min, gerbils avoided the closed arms in favor of the open arms and diazepam increased open-arms entries; furthermore, a single factor (escape behavior) explained all the analyzed measures. Only after 5-min, gerbils reduced open-arms exploration and three independent factors emerged for each subsequent 5-min bin. These findings suggest that EPM data from gerbils should be analyzed in at least two 5-min bins. Measures from the standard 5-min session seem to be related to an escape response from the EPM through the open arms. Once habituated, measures from the second 5-min bin seem to be related to a conflictive situation: keep trying to escape unsuccessfully (due to open-arms height) or seek protection in the closed arms (unsafe places). Diazepam seems to reduce this conflict by mitigating the escape response (Factor 1 - Anxiety) and increasing closed-arms approach (Factor 2) and risk assessment (Factor 3). Unlike mice and rats, a decrease in open-arms exploration and an increase in risk assessment could be interpreted as an anxiolytic-like effect in gerbils.

Gerbils exhibit stable open-arms exploration across repeated testing on the elevated plus-maze.

Repeated testing on the elevated plus-maze (EPM) leads rats and mice to avoid the open-arms of the apparatus. The effect of multiple exposures to the EPM on the behavioral profile of gerbils is unknown. In this study, young and middle-aged gerbils were exposed to the EPM and four retests were carried out 24, 48, 72 and 96h after the first trial in order to determine whether animals exhibited open-arms avoidance. In addition, groups of young and middle-aged gerbils were exposed to the EPM for 20-min followed by a 5-min retest trial 24h apart to analyze the effect of a prolonged exposure to the EPM on open-arms exploration during first trial and retest. Gerbils exhibited high exploration of open-arms during the first trial and progressive locomotor decrease across repeated testing. Unlike previous reports for rats and mice, young gerbils showed a stable open-arms exploration both across multiple exposures and during a prolonged exposure to EPM. Middle-aged gerbils also exhibited a stable open-arms exploration during retest prior to the 20-min test. Results suggest a reliable repeated test paradigm for the EPM using our proposed methodology for gerbils.

Ethopharmacological analysis of the open elevated plus-maze in mice.

Exposure of rodents to an open elevated plus-maze (oEPM) elicits antinociception and increases plasma corticosterone levels. However, no studies have yet assessed the defensive behaviour repertoire of animals in this modified test. In Experiment 1, factor analysis was employed to characterise the behavioural profile of mice exposed to the oEPM. Experiments 2 and 3 assessed the effects of acute alprazolam (0.5-1.5mg/kg; diazepam 0.5-1.5mg/kg), pentylenetetrazole (10.0-30.0mg/kg), yohimbine (2.0-6.0mg/kg), mCPP (0.3-3.0mg/kg), and acute and chronic fluoxetine (10.0-30.0mg/kg) and imipramine (1.0-15.0mg/kg) on behaviours identified in Experiment 1. The factor analyses revealed that behaviour in the oEPM can largely (77% total variance) be accounted for in terms of 3 factors: factor 1 ('depth exploration'; e.g. head-dipping on the arms), factor 2 ('cautious exploration of arms'; e.g. flatback approach), and factor 3 ('risk assessment'; stretched attend postures - SAP). Experiments 2 and 3 showed that, over the dose range used, alprazolam selectively attenuated all measures of defensiveness. Similar, though more modest, effects were seen with diazepam. Confirming the intensity of the emotional response to the oEPM (nociceptive, endocrine and behavioural), relatively few significant behavioural changes were seen in response to the anxiogenic compounds tested. Although acute fluoxetine or imipramine treatment failed to modify behaviour in the oEPM, chronic fluoxetine (but not chronic imipramine) attenuated total flat back approach and increased head dipping outside the central square. Together, the results indicate that the oEPM induces behavioural defensive responses that are sensitive to alprazolam and chronic fluoxetine.

Ethopharmacological evaluation of the rat exposure test: a prey-predator interaction test.

The rat exposure test (RET) is a prey (mouse)-predator (rat) situation that activates brain defensive areas and elicits hormonal and defensive behavior in the mouse. Here, we investigated possible correlations between the spatiotemporal [time spent in protected (home chamber and tunnel) and unprotected (surface) compartments and frequency of entries into the three compartments] and ethological [e.g., duration of protected and unprotected stretched-attend postures (SAP), duration of contact with the rat's compartment] measures (Experiment 1). Secondly, we investigated the effects of systemic treatment with pro- or anti-aversive drugs on the behavior that emerged from the factor analysis (Experiment 2). The effects of chronic (21 days) imipramine and fluoxetine on defensive behavior were also investigated (Experiment 3). Exp. 1 revealed that the time in the protected compartment, protected SAP and rat contacts loaded on factor 1 (defensive behavior), while the total entries and unprotected SAP loaded on factor 2 (locomotor activity). Exp. 2 showed that alprazolam (but not diazepam) selectively changed the defensive factor. Caffeine produced a mild proaversive-like effect, whereas yohimbine only decreased locomotor activity (total entries). Fluoxetine (but not imipramine) produced a weak proaversive-like effect. 5-HT(1A)/5-HT(2) receptor ligands did not change any behavioral measure. In Exp. 3, chronic fluoxetine (but not imipramine) attenuated the defensive behavior factor without changing locomotion. Given that the defensive factor was sensitive to drugs known to attenuate (alprazolam and chronic fluoxetine) and induce (caffeine) panic attack, we suggest the RET as a useful test to assess the effects of panicolytic and panicogenic drugs.

Neonatal exposure to LPS leads to heightened exploratory activity in adolescent rats.

Although several reports have demonstrated physiological and behavioral changes in adult rats due to neonatal immune challenges, little is known about their effects in adolescence. Since neonatal exposure to lipopolysaccharide (LPS) alters the neural substrates involved in cognitive disorders, we tested the hypothesis that it may also alter the response to novel environments in adolescent rats. At 3 and 5 days of age, male Wistar rats received intraperitoneal injections of either vehicle solution or E. coli LPS (0.05mg/kg) or were left undisturbed. In the mid-adolescent period, between 40 and 46 days of age, the rats were exposed to the following behavioral tests: elevated plus-maze, open-field, novel-object exploration task, hole-board and the modified Porsolt forced swim test. The results showed that, in comparison with control animals, LPS-treated rats exhibited (1) less anxiety-related behaviors and enhanced patterns of locomotion and rearing in the plus-maze and the open-field tests, (2) high levels of exploration of both objects in the novel-object task and of corner and central holes in hole-board test, and (3) more time spent diving, an active behavior in the forced swim test. The present findings suggest that neonatal LPS exposure has long-lasting effects on the behavior profile adolescent rats exhibit in response to novelty. This behavioral pattern, characterized by heightened exploratory activity in novel environments, also suggests that early immune stimulation may contribute to the development of impulsive behavior in adolescent rats.

Ansiedad y mied:: su valor adaptativoy maladaptacioess / Fear and nxiety:: adaptive value and maladaptations

The set of answers emitted by the organisms in response to a real or potential danger is called the Anxiety State. This state, of evolutionary importance, appears when a strong danger or risk is detected, and in response to ambiguous threat stimuli that could be of innate or learned nature. A low level of anxiety is beneficial for the animals as a fundamental resource of protection of the individual against physical and social dangers. The neural basis responsible by such states would be the oldest cerebral areas, preserved in many species, that are crucial for the control of the emotions, and whosemalfunctions lead to mood disorders. Many experimental models have been developed to help the study of behaviors and neural basis of the anxiety state, providing tools that collaborate not only to the therapeutics of pathologies, but also to the better understanding of the world of the emotions.

El conjunto de respuestas emitidas por diferentes especies frente a un peligro real o potencial se conoce como Estado de Ansiedad. Este estado, de importancia evolutiva para las especies, aparece cuando se detecta un peligro o amenaza o ante la presencia de estímulos ambiguos, innatos o aprendidos, que indican una amenaza. Así, un determinado nivel de ansiedad es benéfico para los animales, siendo un recurso fundamental de protección contra peligros físicos y sociales. Los substratos neurales responsables por tales estados, corresponden a áreas cerebrales antiguas, preservadas en muchas especies y críticas para el control de las emociones que al sufrir alteraciones en su funcionamiento producen disturbios del comportamiento. Diversos modelos experimentales se han desarrollado para estudiar los componentes conductuales y sustratos neurales implicados en el estado de ansiedad y su utilización ya está suministrando herramientas para complementar la comprensión de diversas patologías y conocimiento del mundo de las emociones.