Stress effects on spatial memory retrieval and brain c-Fos expression pattern in adults are modulated by early nicotine exposure.

The cognitive effects of nicotine are linked to persistent modifications in extended neural systems that regulate cognitive and emotional processes, and these changes occur during development. Additionally, acute stress has modulatory effects on cognition that involve broad neural systems and can be influenced by prior environmental challenges. The effects of nicotine and stress may be interconnected, leading to modifications in a network of shared brain substrates. Here, we explored the interaction between nicotine and stress by evaluating the effects of acute stress exposure in spatial memory retrieval for animals pretreated with nicotine during adolescence or adulthood. Adolescent (35 days old) and adult (70 days old) male Wistar rats were treated for 21 days with one daily subcutaneous injection of nicotine 0.14 mg/ml (free base). 30 days after the last injection, rats were trained in the Barnes maze and tested 24 h later, half the rats were tested under regular conditions, and half of them were exposed to 1 h of restraining stress before the retrieval test, and brain samples were collected and c-Fos immunopositive cells were stained. Prolonged nicotine withdrawal or acute stress improved spatial memory retrieval. Acute stress in nicotine pretreated adults impaired spatial memory retrieval. Nicotine exposure during early adulthood resulted in long-lasting brain adaptations that amplified emotional responses to acute stress after prolonged drug withdrawal.

Interaction of nicotine and social reward in group-reared male adolescent rats.

Adolescents exhibit great sensitivity to nicotine and social interaction; accordingly, when both stimuli are presented together, they interact to enhance the incentive value of the context in which they occur. Noteworthy, most studies assessing the interaction between nicotine and social reward have used isolated-reared rats. Adolescent isolation is an adverse condition that impacts brain development and behavior, so it is not known if the interaction also occurs in rats without social deprivation. The present study used a conditioned place preference model (CPP) to examine the interaction between nicotine and social reward in group-reared male adolescent rats. At weaning, Wistar rats were randomly assigned to four groups: vehicle, vehicle and a social partner, nicotine (0.1 mg/Kg s.c.), and nicotine and a social partner. Conditioning trials occurred on eight consecutive days followed by a test session in which the preference change was assessed. Besides the establishment of CPP, we examined the effects of nicotine on (1) social behaviors during CPP trials and (2) tyrosine hydroxylase (TH) and oxytocin (OT) as markers of changes in the neuronal mechanisms for reward and social affiliation. Similar to previous results, the joint presentation of nicotine and social reward induced CPP, whereas either nicotine or social interaction presented alone did not. This finding coincided with an increase in TH levels observed after nicotine administration only in socially conditioned rats. The interaction between nicotine and social reward is not related to the effects of nicotine on social investigation or social play.

Hemispheric asymmetry in the processing of an emotional working memory task.

Emotion and working memory are key components in daily life experiences. Previous research has already established a connection between these processes but the neural substrates of this relationship remain an open discussion. The present study aimed to investigate the effects of the use of pictures with emotional valence on the performance of a working memory task as well as the neuronal response during the task. For this purpose, 32 participants performed a 2-back task with negative, positive, and neutral images selected from the International Affective Pictures System (IAPS). No significant difference was found in the performance or in the response time related to the valence of the images. Repeated-measures ANOVA with hemisphere and valence as factors revealed an increase of the activity in the right hemisphere for the amplitude of the ERP P3 component and for the time-locked theta power for all the images. The P3 component in the right hemisphere additionally showed greater mean amplitude for the negative images as compared to the neutral and positive ones. Together, these results suggest a predominant role of the right hemisphere for the processing of both working memory and emotional information, as well as a higher neuronal resource allocation to the processing of negative valence images which enabled a proper performance of the working memory task for the negative images.

Post-weaning social isolation increases the incentive value of nicotine-related contexts and decreases the accumulation of ΔFosB in nucleus accumbens in adolescent rats.

Adolescent social conditions profoundly affect vulnerability to drug abuse. Preclinical studies have shown that preventing social interactions during adolescence increases the rewarding effects of drugs like alcohol, cocaine, or amphetamines, however, little data exist regarding the impact of social isolation on nicotine effects. The current study evaluated the effects of differential rearing conditions during adolescence (isolation or group rearing) on (1) conditioned place preference induced by low nicotine doses (0.1 or 0.3 mg/kg) and (2) sensitization to the locomotor effects of nicotine after sub-chronic administration (3) and accumulation of ΔFosB in nucleus accumbens (NAc). Results showed that nicotine induced place preference in isolated and grouped rats, but the effect was more persistent for the rats reared in isolation. Isolated reared rats also exhibited lower levels of ΔFosB accumulation in NAc. No differences were found in the behavioral sensitization to nicotine effects between rearing conditions. The results suggest that isolation engenders a more robust incentive value of nicotine-related contexts. This effect could be related to the basal expression of ΔFosB: lower levels of this transcription factor seem to impair the motivation of isolated reared rats and increase their vulnerability to the effects of drugs like nicotine.

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.

Overtraining modifies spatial memory susceptibility to corticosterone administration.

Even though the effects of overtraining and glucocorticoids on different phases of spatial memory are known, the interaction between these factors on the retrieval and extinction of spatial memory has not yet been described. Adult male Wistar rats received eight training trials per day in the Barnes maze for either one or two days. Twenty-four hours after the last training trial they were randomly assigned for receiving an intraperitoneal vehicle or corticosterone injection (0.125 or 0.5 mg/kg) and ten minutes later they were given a memory test, followed by seven extinction trials. Extinction retention was evaluated twenty-four hours after extinction. The second training session did not provoke significant changes regarding escape latency nor weighted errors, thereby showing that overtraining had been obtained. The overtrained animals performed better than the trained ones during the retrieval test. Corticosterone administration did not affect the overtrained animals' performance; by contrast, only the lower dose impaired trained animals' retrieval. Overtrained subjects acquired extinction more rapidly than those which received just one session, but corticosterone did not significantly modify extinction. However, whilst the spatial task remained extinguished in trained animals during the extinction retrieval test, spontaneous recovery occurred in overtrained animals. Such training intensity effects on extinction retrieval were reverted by corticosterone. Overall, these results suggested that overtraining modified the susceptibility of spatial memory's trace to the effects of corticosterone on retrieval and extinction.

Vibrissal paralysis produces increased corticosterone levels and impairment of spatial memory retrieval.

This research was aimed at establishing how the absence of active whisking in rats affects acquisition and recovery of spatial memory. The mystacial vibrissae were irreversibly paralyzed by cutting the facial nerve's mandibular and buccal branches bilaterally in the facial nerve lesion group (N=14); control animals were submitted to sham-surgery (N=15). Sham-operated (N=11) and facial nerve-lesioned (N=10) animals were trained (one session, eight acquisition trials) and tested 24h later in a circular Barnes maze. It was found that facial nerve lesioned-animals adequately acquired the spatial task, but had impaired recovery of it when tested 24h after training as compared to control ones. Plasma corticosterone levels were measured after memory testing in four randomly chosen animals of each trained group and after a single training trial in the maze in additional facial nerve-lesioned (N=4) and sham-operated animals (N=4). Significant differences respecting the elevation of corticosterone concentration after either a single training trial or memory testing indicated that stress response was enhanced in facial nerve-lesioned animals as compared to control ones. Increased corticosterone levels during training and testing might have elicited the observed whisker paralysis-induced spatial memory retrieval impairment.

Efectos de la inactivación sistémica de los receptores GR y MR sobre el daño rápido en la recuperación de la memoria espacial inducido por corticosterona / Systemic Inactivation of GR and MR Receptors on Corticosterone-induced rapid damage in Spatial Memory Recovery

Estudios previos de nuestro laboratorio han mostrado que diez minutos después de la administración sistémica de corticosterona se dificulta la recuperación de la memoria espacial en el laberinto de Barnes, sin embargo se desconocen los mecanismos que subyacen a este efecto. Dado que los glucocorticoides ejercen sus acciones a través de los receptores de tipo GR y MR, en el presente estudio se evaluó la participación de estos receptores en el efecto perjudicial rápido de la corticosterona sobre la memoria espacial. Para ello 37 ratas Wistar macho fueron entrenadas en la tarea y 24h después recibieron una inyección subcutánea de antagonista GR, antagonista MR o vehículo. 50min después los animales fueron inyectados con corticosterona o vehículo por vía intraperitoneal y 10min después se evaluó la recuperación de la memoria espacial. Los resultados mostraron que la corticosterona perjudicó rápidamente la recuperación de la memoria espacial a largo plazo, pues los animales inyectados con esta hormona presentaron mayores latencias de escape, mayor número de errores, mayor número de exploraciones y mayor distancia recorrida hasta alcanzar la meta; un efecto revertido solamente con la administración del antagonista MR. Este hallazgo concuerda con estudios in vitro donde se muestra que los efectos rápidos de la corticosterona sobre la trasmisión glutamatérgica en el hipocampo están mediados por los receptores MR.

Previous studies of our laboratory have shown that it is difficult to recover the spatial memory in the Barnes maze ten minutes after a systemic administration of corticosterone; however the mechanisms that underlie this effect are unknown. Considering glucocorticoids exert their actions through GR and MR type receptors, the present study evaluated the participation of these receptors in the rapid damaging effect of corticosterone on spatial memory. For this, 37 male Wistar rats were trained on the task and 24 h afterwards they received a subcutaneous injection of GR antagonist, MR antagonist or vehicle. 50 min later the animals were injected with corticosterone or vehicle intraperitoneally and 10 min later, the spatial memory recovery was evaluated. The results indicated that corticosterone rapidly impaired spatial long-term memory recovery, as animals injected with this hormone presented higher escape latencies, more errors, higher exploration and greater traveled distance to reach the goal; an effect reverted only with the administration of the MR antagonist. This finding agrees with in vitro studies showing that the rapid effects of corticosterone on glutamatergic transmission in the hippocampus are mediated by MR receptors.

Histone deacetylase inhibition abolishes stress-induced spatial memory impairment.

Acute stress induced before spatial training impairs memory consolidation. Although non-epigenetic underpinning of such effect has been described, the epigenetic mechanisms involved have not yet been studied. Since spatial training and intense stress have opposite effects on histone acetylation balance, it is conceivable that disruption of such balance may underlie acute stress-induced spatial memory consolidation impairment and that inhibiting histone deacetylases prevents such effect. Trichostatin-A (TSA, a histone deacetylase inhibitor) was used to test its effectiveness in preventing stress' deleterious effect on memory. Male Wistar rats were trained in a spatial task in the Barnes maze; 1-h movement restraint was applied to half of them before training. Immediately after training, stressed and non-stressed animals were randomly assigned to receive either TSA (1mg/kg) or vehicle intraperitoneal injection. Twenty-four hours after training, long-term spatial memory was tested; plasma and brain tissue were collected immediately after the memory test to evaluate corticosterone levels and histone H3 acetylation in several brain areas. Stressed animals receiving vehicle displayed memory impairment, increased plasma corticosterone levels and markedly reduced histone H3 acetylation in prelimbic cortex and hippocampus. Such effects did not occur in stressed animals treated with TSA. The aforementioned results support the hypothesis that acute stress induced-memory impairment is related to histone deacetylation.

Acute restraint stress and corticosterone transiently disrupts novelty preference in an object recognition task.

The object recognition task is a procedure based on rodents' natural tendency to explore novel objects which is frequently used for memory testing. However, in some instances novelty preference is replaced by familiarity preference, raising questions regarding the validity of novelty preference as a pure recognition memory index. Acute stress- and corticosterone administration-induced novel object preference disruption has been frequently interpreted as memory impairment; however, it is still not clear whether such effect can be actually attributed to either mnemonic disruption or altered novelty seeking. Seventy-five adult male Wistar rats were trained in an object recognition task and subjected to either acute stress or corticosterone administration to evaluate the effect of stress or corticosterone on an object recognition task. Acute stress was induced by restraining movement for 1 or 4h, ending 30 min before the sample trial. Corticosterone was injected intraperitoneally 10 min before the test trial which was performed either 1 or 24h after the sample trial. Four-hour, but not 1-h, stress induced familiar object preference during the test trial performed 1h after the sample trial; however, acute stress had no effects on the test when performed 24h after sample trial. Systemic administration of corticosterone before the test trial performed either 1 or 24h after the sample trial also resulted in familiar object preference. However, neither acute stress nor corticosterone induced changes in locomotor behaviour. Taken together, such results suggested that acute stress probably does not induce memory retrieval impairment but, instead, induces an emotional arousing state which motivates novelty avoidance.

Efecto de la exposición a un protocolo de estrés social agudo sobre los niveles sistémicos de cortisol y la ejecución de una tarea de atención sostenida y dividida / Efeito da exposição a um protocolo de estresse social agudo sobre os níveis sistêmicos de cortisol e a execução de uma tarefa de atenção sustentada e dividida / Effects of exposure to an acute social stress protocol on systemic levels of cortisol and on the execution of a sustained and divided attention task

La presente investigación tuvo como objetivo determinar los efectos del estrés social agudo inducido experimentalmente con una versión modificada del TSST (Trier Social Stress Test), en los niveles sistémicos de la hormona cortisol y en la ejecución de una tarea de atención sostenida y dividida, en estudiantes universitarios de ambos sexos. Los resultados mostraron que el protocolo modificado del TSST produjo incrementos en los niveles sistémicos de cortisol en los participantes de sexo masculino, pero no afectó la ejecución en la prueba PASAT (Paced Auditory Serial Addition Task). Se discuten estos resultados a la luz de trabajos previos en los que se observan diferencias por género en los efectos del estrés.

A presente pesquisa teve como objetivo determinar os efeitos do estresse social agudo induzido experimentalmente com uma versão modificada do TSST (Trier Social Stress Test), nos níveis sistêmicos do hormônio cortisol e na execução de uma tarefa de atenção sustentada e dividida, em estudantes universitários de ambos os sexos. Os resultados mostraram que o protocolo modificado do TSST produziu aumento nos níveis sistêmicos de cortisol nos participantes de sexo masculino, mas não afetou a execução na prova PASAT (Paced Auditory Serial Addition Task). Discutem-se esses resultados à luz de trabalhos prévios nos quais se observam diferenças por gênero nos efeitos do estresse.

This research project examined the effects of acute social stress induced experimentally with a modified version of TSST (Trier Social Stress Test) on the systemic levels of the cortisol hormone and on the execution of a sustained and divided attention task, in male and female university students. Results showed that the modified TSST protocol caused increases in the systemic levels of cortisol in male participants, but did not affect the execution of the PASAT (Paced Auditory Serial Addition Task). The results are discussed in the light of previous studies in which gender differences in the effects of stress are observed.

Divergent short- and long-term effects of acute stress in object recognition memory are mediated by endogenous opioid system activation.

Acute stress induces short-term object recognition memory impairment and elicits endogenous opioid system activation. The aim of this study was thus to evaluate whether opiate system activation mediates the acute stress-induced object recognition memory changes. Adult male Wistar rats were trained in an object recognition task designed to test both short- and long-term memory. Subjects were randomly assigned to receive an intraperitoneal injection of saline, 1 mg/kg naltrexone or 3 mg/kg naltrexone, four and a half hours before the sample trial. Five minutes after the injection, half the subjects were submitted to movement restraint during four hours while the other half remained in their home cages. Non-stressed subjects receiving saline (control) performed adequately during the short-term memory test, while stressed subjects receiving saline displayed impaired performance. Naltrexone prevented such deleterious effect, in spite of the fact that it had no intrinsic effect on short-term object recognition memory. Stressed subjects receiving saline and non-stressed subjects receiving naltrexone performed adequately during the long-term memory test; however, control subjects as well as stressed subjects receiving a high dose of naltrexone performed poorly. Control subjects' dissociated performance during both memory tests suggests that the short-term memory test induced a retroactive interference effect mediated through light opioid system activation; such effect was prevented either by low dose naltrexone administration or by strongly activating the opioid system through acute stress. Both short-term memory retrieval impairment and long-term memory improvement observed in stressed subjects may have been mediated through strong opioid system activation, since they were prevented by high dose naltrexone administration. Therefore, the activation of the opioid system plays a dual modulating role in object recognition memory.

Characterizing spatial extinction in an abbreviated version of the Barnes maze.

Adult male Wistar rats were trained to find an escape box in the Barnes maze in order to characterize the extinction process of a learned spatial preference. To do so, once they had fully acquired the spatial task, they were repeatedly exposed to the maze without the escape box. Multiple behavioral measurements (grouped into motor skill and spatial preference indicators) were followed up throughout the complete training process. Animals gained efficiency in finding the escape box during acquisition, as indicated by the reduction in the time spent escaping from the maze, the number of errors, the length of the traveled path, and by the increase in exploration accuracy and execution speed. When their retention and preference were tested 24h later, all the subjects retained their enhanced performance efficiency and accuracy and displayed a clear-cut preference for the escape hole and its adjacent holes. Almost all motor skill indicators followed an inverse, though not monotonic, pattern during the extinction training, returning to basal levels after three trials without escape box, displaying a transient relapse during the fifth extinction trial. Preference indicators also followed a reverse pattern; however, it took seven trials for them to return to basal levels, relapsing during the eighth extinction trial. The abbreviated Barnes maze acquisition, evaluation, and extinction procedures described herein are useful tools for evaluating the effects of behavioral and/or pharmacological treatment on different stages of spatial memory, and could also be used for studying the neurophysiological and neurobiological underpinnings of this kind of memory.

El estrés agudoiinterfiere con la evocación y pomueve la extinción de la memorria espacial en el laberinto de barnes / High stress interfers with evocation and promotes extintion of spatial memory in the Barnes maze

Para evaluar los efectos del estrés agudo sobre la recuperación y la extinción de la memoria espacial, se utilizaron ratas entrenadas en el laberinto circular de Barnes. El entrenamiento consistió de 8 ensayos de adquisición (intervalo entre ensayos, IEE, de 5 min) en donde los animales debían aprender a encontrar una caja meta ubicada en uno de los 18 agujeros del laberinto. Todos los animales adquirieron el aprendizaje espacial, ya que invirtieron menos tiempo en encontrar la caja meta y cometieron menos errores a medida que se sucedían los ensayos de entrenamiento. Veinticuatro horas después del entrenamiento se evaluó la retención y extinción del aprendizaje espacial mediante una prueba con caja meta (PCC) seguida de siete pruebas sin caja (PSC), con un IEE de 5 min. Una hora y media antes de la sesión de evaluación de la memoria un grupo de animales fue sometido a estrés por restricción de movimientos durante una hora, permitiéndoles un período de recuperación de 30 min y otro grupo permaneció en su caja hogar sin manipulación (control). Los resultados indican que el estrés deteriora el proceso de evocación de la memoria espacial, ya que los animales estresados cometieron un mayor número de errores y demoraron más tiempo en encontrar la caja meta durante la PCC , respecto de los controles. Además, el estrés facilita el proceso de extinción, ya que, durante las PSCs los animales estresados no mostraron una persistencia en la exploración del agujero que, en el entrenamiento, conducía a la caja meta.

To evaluate the effects of acute stress on evocation and extinction of a spatial memory task, we used rats trained in the Barnes circular maze. The training protocol consisted of eight acquisition trials (intertrial interval, ITI; 5 min) where animals must learn to find an escape box placed under one of these eighteen holes of the maze. All animals learned the spatial memory task as indicated by diminished escape latency and weighted errors along the eight acquisition trials. Twenty four hours after training spatial memory evocation and extinction were tested (one trial with escape box, and seven consecutive trials without escape box, ITI: 5 min). One hour and a half before memory evaluation session half of the animals underwent movement restriction during one hour (one hour stress, 1H) and were allowed 30 min to recover, while the other half stayed in their home cage without manipulation (control, C). Stressed animals displayed a significant increase both in escape latency and in weighted errors during the trial with scape box. These results indicate that movement restriction-induced stress deteriorates the spatial memory evocation. Moreover, movement restriction-induced stress during one hour facilitates extinction, showed by the non-persistence in the exploration of the escape hole during the trials without escape box.

Vibrissal paralysis unveils a preference for textural rather than positional novelty in the one-trial object recognition task in rats.

In order to explore the role of active whisking in object novelty detection, the performance of rats having bilateral vibrissal paralysis was compared to that of non-lesioned animals in three modified versions of the one-trial object recognition task performed in the dark. Vibrissal paralysis was induced by crushing the buccal and mandibular branches of the facial nerve. Lesioned animals were not different from non-lesioned ones in terms of weight-gain, locomotive activity, motivation to explore, and ability to become habituated to a given environment. Only lesioned animals were unable to discriminate a change in object texture as novelty cue in the first task, designed to test textural novelty detection. In the second task, designed to test positional novelty detection, both lesioned and non-lesioned subjects were able to discriminate a change in object position as novelty cue. In the third task, designed to force the subjects to choose between two conflicting novelty cues (texture and position), non-lesioned subjects displayed a clear-cut preference for textural novelty while subjects having bilateral vibrissal paralysis preferred positional novelty. According to these results, active whisking is necessary for textural, but not for positional novelty detection. Moreover, these results indicate that textural novelty in non-lesioned animals seems to overcome positional novelty if these are in competition in an object recognition memory task.

Effects of reversible inactivation of the medial septum on rat exploratory behavior in the elevated plus-maze using a test-retest paradigm.

The effect of intraseptal injections of lidocaine before a first or a second session in the elevated plus-maze, in a test-retest paradigm, was investigated. In addition to gross session analyses, a minute-by-minute analysis of the sessions was used to evaluate both anxiety and memory. Lidocaine injections before the test session produced increases in the frequency of entries, time spent and distance run in the open arms without affecting activity occurring in the closed arms. During the retest session, saline- and lidocaine-treated rats exhibited increased indices of anxiety and lidocaine-treated rats exhibited decreased closed-arm entries. The minute-by-minute analysis showed a faster decrease in anxiety-related behaviors during the test session by saline- than by lidocaine-treated rats and a significant decrease in closed-arm exploration by saline-treated rats, but not by lidocaine-treated ones. Lidocaine injection before the retest session produced increases in the frequency of entries, time spent and distance run in the open arms in the second session when compared with saline-treated rats. Minute-by-minute analysis showed an increase in the time spent in the open arms by lidocaine animals at the beginning of the retest session in comparison to saline animals and a significant decrease in closed-arm exploration by both groups. These results suggest that inactivation of the medial septum by lidocaine affects the expression of unconditioned and conditioned forms of anxiety in the elevated plus-maze and, in a lesser way, the acquisition and retention of spatial information.

Efecto de la restricción calórica en el aprendizaje y la recuperación de una tarea espacial en ratas expuestas a estrés agudo / Effects of caloric restriction on learning and recovery of a spatial task in rats exposed to acute stress

En el presente estudio son descritos los efectos de la restricción calórica en el aprendizaje y larecuperación de una tarea espacial en animales estresados antes de la recuperación de una tareade aprendizaje espacial en el laberinto circular de Barnes. Para esto, ratas Wistar macho fueronsometidas a las condiciones: Ad libitum (AL) o Ayuno Intermitente (AI) durante un periodo de dosmeses, luego del cual, ambos grupos fueron expuestos a una forma experimental de estrés agudo através de la técnica de restricción de movimientos durante cuatro horas. Los sujetos AI mejoraron enlas medidas de aprendizaje durante los primeros ensayos de la adquisición de la tarea, mientrasque en la fase de evaluación, luego de aplicado el estresor, necesitaron más tiempo para realizar latarea. Estos resultados son discutidos a la luz de los resultados descritos anteriormente en laliteratura enfatizando las diferencias existentes entre los instrumentos utilizados para la evaluacióndel aprendizaje espacial y su posible interacción con el estrés inducido experimentalmente.

The purpose of the present study was to describe the effects of caloric restriction on spatial learningand recovery in the Barnes maze in animals experimentally stressed before recovery of the spatial task. Male Wistar rats were exposed for two months to one of two conditions: ad libitum (AL) orintermittent fasting (IF). Both groups were exposed then to an experimental form of acute stress,induced by movement restriction for 4 hours. IF subjects had better performance in learning tasksduring the acquisition trials but required more time to complete the task after the stressor wasapplied. These results are discussed in light of previous data reported in the literature emphasizingdifferences in the instruments used to evaluate spatial learning and its interaction with experimentallyinduced stress.

The role of vision and proprioception in the aversion of rats to the open arms of an elevated plus-maze.

The elevated plus-maze test is usually run with a short edge surrounding the open arms in order to prevent the rats from falling. The present experiment investigated the role of transparent edges differing in heights: 1 (used as control), 5, 10, 20 and 40 cm, the latter the same height as the closed arm walls. Additionally, this 40-cm high transparent edge was also studied covered by white translucent or black opaque paper. The data show that the time spent in the open arms was significantly greater when the edge height was 5, 10 or 40 cm covered by the white or black paper. However, there were no differences from the 1-cm control edge when the height was 40 cm transparent. A similar effect was observed when entries in the open arms and total entries were analyzed. The facts that there were no differences when the open arms were surrounded by 1- or 40-cm transparent edges (which allow thigmotaxis) and that the same 40-cm edge caused increases in exploratory behavior when covered by papers indicate that vision triggers aversion to open spaces.

The distribution of fos immunoreactivity in rat brain following freezing and escape responses elicited by electrical stimulation of the inferior colliculus.

Several sources of evidence indicate that the inferior colliculus also integrates acoustic information of an aversive nature besides its well-known role as a relay station for auditory pathways. Gradual increases of the electrical stimulation of this structure cause in a hierarchical manner alertness, freezing and escape behaviors. Independent groups of animals implanted with bipolar electrodes into the inferior colliculus received electrical stimulation at one of these aversive thresholds. Control animals were submitted to the same procedure but no current was applied. Next, analysis of Fos protein expression was used to map brain areas activated by the inferior colliculus stimulation at each aversive threshold and in the controls. Whereas alertness elicited by stimulation of the inferior colliculus did not cause any significant labeling in any structure studied in relation to the respective control, electrical stimulation applied at the freezing threshold increased Fos-like immunoreactivity in the central amygdaloid nucleus and entorhinal cortex. In contrast, escape response enhanced Fos-like immunoreactivity in the nucleus cuneiform and the dorsal periaqueductal gray matter of the mesencephalon. This evidence supports the notion that freezing and escape behaviors induced by electrical stimulation of the inferior colliculus activate different neural circuitries in the brain. Both defensive behaviors caused significant expression of c-fos in the frontal cortex, hippocampus and basolateral amygdaloid nucleus. This indistinct pattern of c-fos distribution may indicate a more general role for these structures in the modulation of fear-related behaviors. Therefore, the present data bring support to the notion that amygdala, dorsal hippocampus, entorhinal cortex, frontal cortex, dorsal periaqueductal gray matter and cuneiform nucleus altogether play a role in the integration of aversive states generated at the level of the inferior colliculus.