Open-field Session Research Articles

Alteration of Lateral Habenula Function Prevents the Proper Exploration of a Novel Environment

The lateral habenula (LHb) is an epithalamic brain region viewed as a converging hub, integrating information from a large connectome and then projecting to few critical midbrain monoaminergic systems. Numerous studies have explored the roles of the LHb, notably in aversion and avoidance. An important recurring finding when manipulating the LHb is the induction of anxiety-related behaviours. However, its exact role in such behaviours remains poorly understood. In the present study, we used two pharmacological approaches altering LHb activity, intra-LHb infusion of either the GABA-A receptor agonist, Muscimol, or the glutamatergic AMPA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and exposed rats to three consecutive open field (OF) sessions. We found that both pharmacological treatments prevented rats to explore the centre of the OF, considered as the most anxiogenic part of the apparatus, across the three OF sessions. In addition, during the first, but not the two consecutive sessions, both treatments prevented a thorough exploration of the OF. Altogether, these results confirm the crucial role played by the LHb in anxiety-related behaviours and further suggest its implication in the exploration of new anxiogenic environments.

Forced swimming stress increases natatory activity of lead-exposed mice.

Recent evidence points to the relationship between lead toxicity and the function of the hypothalamic-pituitary-adrenal axis, which suggests that lead exposure could influence how an individual cope with stress. Here we test this hypothesis by investigating the behavioral effects of lead exposure in mice during the forced swimming test (FST), a parading in which animals are exposed to a stressful situation and environment. Swiss mice received either 180ppm or 540ppm of lead acetate (Pb) in their ad-lib water supply for 60-90days, starting at postnatal day 30. Control (Ctrl) mice drank tap water. At the end of the exposure period, mice were submitted to a 5-min session of FST or to an open-field session of the same duration. Data from naïve animals showed that corticosterone levels were higher for animals tested in the FST compared to animals tested in the open-field. Blood-lead levels (BLL) in Pb-exposed mice ranged from 14.3 to 106.9µg/dL. No differences were observed in spontaneous locomotion between Ctrl and Pb-exposed groups in the open-field. However, in the FST, Pb-treated mice displayed higher swimming activity than Ctrl ones and this effect was observed even for animals with BLL higher than 20µg/dL. Furthermore, significant differences in brain glutathione levels, used as an indicator of led toxicity, were only observed for BLL higher than 40µg/dL. Overall, these findings suggest that swimming activity in the FST is a good indicator of lead toxicity and confirm our prediction that lead toxicity influences behavioral responses associated to stress.

Voluntary exercise ameliorates anxiogenic effects of acute methamphetamine exposure in Swiss-Webster mice.

The present experiment examined the ability of voluntary exercise (i.e., home-cage wheel running; HCWR) to ameliorate anxiety-like behavior associated with acute methamphetamine exposure in male, Swiss-Webster mice. Mice were permitted access to home-cage running wheels (Exercise), locked home-cage running wheels or no home-cage running wheels (Sedentary) for 6 weeks and then exposed to different methamphetamine doses (vehicle, 0.25, 0.5, or 1.0 mg/kg) once weekly during an 8 h open-field session for 4 weeks. Group differences in hypothalamic-pituitary-adrenal (HPA) activity also were assessed by weighing adrenal glands. It was found that HCWR ameliorated anxiety-like behavior after an injection of either the 0.5 or 1.0 mg/kg methamphetamine dose. Adrenal weights did not differ between Exercise and Sedentary mice. Taken together, these results suggest that voluntary exercise ameliorates the anxiogenic effects of methamphetamine depending on the dose, perhaps via a non-HPA mechanism.

Consistency of Spatial Representations in Rat Entorhinal Cortex Predicts Performance in a Reorientation Task

Goal-directed behavior can be affected by environmental geometry. A classic example is the rectangular arena reorientation task, where subjects commonly confuse opposite but geometrically identical corners [1]. Until recently, little was known about how environmental geometry shapes spatial representations in a neurobehavioral context [2] (although see [3]). In the present study, we asked: Under what circumstances does the internal cognitive map predict behavior? And when does it fail to do so? To this end, we developed a variant of the classical reorientation task that allows for investigation of temporal dynamics of reorientation. We recorded head-direction (HD) cells and grid cells in the medial entorhinal cortex (MEC) of rats before, during, and after performing the task. MEC cells showed a bimodal response of being either aligned or rotated, relative to the free-foraging open-field sessions. Alignment was remarkably stable between disorientations andindicative of corner choice as a function of current and past alignment of spatial representations. Accordingly, when the cells showed consistent andproperly aligned readout across multiple trials, behavioral choices were better predicted by HD and grid cell readout, with a probability of more than 70%. This was not the case when the cells did not show a stable consistent readout. Our findings indicate that entorhinal spatial representations predict corner choice, contingent on the stability and reliability of their readout. This work sets the stage for further studies on the link between the reliability of the neuronal signal and behavior, with implications for many brain systems in many organisms.

Amnesia of inhibitory avoidance by scopolamine is overcome by previous open-field exposure.

The muscarinic cholinergic receptor (MAChR) blockade with scopolamine either extended or restricted to the hippocampus, before or after training in inhibitory avoidance (IA) caused anterograde or retrograde amnesia, respectively, in the rat, because there was no long-term memory (LTM) expression. Adult Wistar rats previously exposed to one or two open-field (OF) sessions of 3 min each (habituated), behaved as control animals after a weak though over-threshold training in IA. However, after OF exposure, IA LTM was formed and expressed in spite of an extensive or restricted to the hippocampus MAChR blockade. It was reported that during and after OF exposure and reexposure there was an increase in both hippocampal and cortical ACh release that would contribute to “prime the substrate,” e.g., by lowering the synaptic threshold for plasticity, leading to LTM consolidation. In the frame of the “synaptic tagging and capture” hypothesis, plasticity-related proteins synthesized during/after the previous OF could facilitate synaptic plasticity for IA in the same structure. However, IA anterograde amnesia by hippocampal protein synthesis inhibition with anisomycin was also prevented by two OF exposures, strongly suggesting that there would be alternative interpretations for the role of protein synthesis in memory formation and that another structure could also be involved in this “OF effect.”

Hippocampus lipid peroxidation induced by residual oil fly ash intranasal instillation versus habituation to the open field

Epidemiological studies have demonstrated the adverse effects of particulate matter (PM) inhalation on the respiratory and cardiovascular systems. It has been reported that air pollution may affect the central nervous system and decrease cognitive function. In rats, residual oil fly ash (ROFA) instillation causes decreased motor activity and increased lipid peroxidation in the striatum and the cerebellum. Our objective was to determine whether chronic instillation of particles induces changes in learning and memory in rats and whether oxidants in the hippocampus may contribute to these adverse effects. Forty-five-day-old male Wistar rats were exposed to ROFA by intranasal instillation and were treated with N-acetylcysteine (NAC) at 150 mg/kg i.p. for 30 days. Control groups were exposed to ROFA, NAC, or neither. On days 1, 8, and 30 of the protocol, rats were submitted to the open field test to evaluate habituation. After the last open field session, the rats were killed by decapitation. The hippocampus was used to determine lipid peroxidation (LP) by the thiobarbituric acid-reactive substances test. ROFA instillation induced an increase in LP in the hippocampus compared to all treatment groups (p = .012). NAC treatment blocked these changes. All of the treatment groups presented a decrease in the frequency of peripheral walking (p = .001), rearing (p = .001), and exploration (p = .001) over time. Our study demonstrates that exposure to particles for 30 days and/or NAC treatment do not modify habituation to an open field, a simple form of learning and memory in rats, and that oxidative damage induced by ROFA does not modulate these processes.

High and low rearing subgroups of rats selected in the open field differ in the activity of K +-stimulated p-nitrophenylphosphatase in the hippocampus

Na +/K +-adenosinetriphosphatase (Na +/K +-ATPase) is of paramount importance for the proper functioning of the organism. The enzyme is involved in several aspects of brain function, such as the repolarization of the neuronal membranes and neurotransmitters uptake/release. Therefore, individual differences in the activity of brain Na +/K +-ATPase may result in differences in the functioning of the brain, which, in consequence, could lead to behavioral divergences. Individual differences in rearing, an exploratory behavior, have been shown to be genetically determined. In rats, the inhibition of the activity of Na +/K +-ATPase was reported to induce changes in the exploratory behavior. The aim of this work was to verify if subgroups of rats selected according to the number of rearings (high and low rearing subgroups) in the open field test differ in the activity of Na +/K +-ATPase in brain regions. Adult, male outbred Wistar rats were selected in the open field test according to the number of rearings in subgroups of high (HR) and low (LR) rearing responders. After a rest of about 20 days after the open field session, HR and LR rats were sacrificed. In the first experiment, frontal cortex, striatum, brainstem, hippocampus and the amygdala (including the overlying limbic cortex) were dissected. The reaction of dephosphorylation of Na +/K +-ATPase (K + stimulated p-nitrophenylphosphatase) was assayed in homogenates rich in synaptosomes. The results obtained showed a statistically significant higher activity of K + p-nitrophenylphosphatase only in the hippocampus of HR subgroup of rats. This result was replicated in two other subsequent experiments with different HR and LR subgroups of rats selected at different times of the year. Our data suggest that the difference in the activity of Na +/K +-ATPase in the hippocampus is innate and is involved in the expression of the rearing behavior.

Ontogenesis of within-session locomotor habituation in the open field

Habituation signifies a decreased response to a constant or repeated stimulus or environment. Although habituation is a fundamental form of nonassociative learning, little is known about its ontogenesis. Here, locomotor activity of postnatal ferrets within individual open field sessions was quantitatively analysed. The patterns of activity revealed a gradual shift across developmental time between relative increment and decrement of activity within sessions. The increment-to-decrement turning point was around postnatal day 48. These novel findings indicate that systematic changes in the interplay between mechanisms that drive exploratory behaviour and those that inhibit it shape the ontogenesis of open field habituation. The remarkable robustness of the data underscores the suitability of the ferret as an experimental animal for investigating ontogenesis of habituation.

Mechanism of the effect of postresuscitation changes in the brain on the dynamics of extinction of orientation and exploratory response in rats

The type of open-field behavior (determined in preliminary tests) was preserved after 10-min circulatory arrest. Postresuscitation changes in the bran modified orientation and exploratory activity under conditions of its partial extinction before clinical death. High behavioral activity of rats in the first open-field session after resuscitation was related to the impairment of memory traces, while that in the follow-up period was associated with the formation of a pathological self-maintaining system between components of orientation and exploratory behavior.

Detection of novelty, but not memory of spatial habituation, is associated with an increase in phosphorylated cAMP response element-binding protein levels in the hippocampus.

There is a growing body of evidence showing that the formation of associative memories is associated with an increase in phosphorylated cAMP response element-binding protein (pCREB) levels. We recently reported increased pCREB levels in the rat hippocampus after an exploration to a novel environment. In the present work, we studied whether this increment in CREB activation is associated with the formation of memory of habituation to a novel environment or with the detection of novelty. Rats were submitted to consecutive open field sessions at 3-h intervals. Measurement of the hippocampal pCREB level, carried out 1 h after each training session, showed that (1) it did not increase when rats explored a familiar environment; (2) it did not increase after a reexposure that improves the memory of habituation; (3) it increased after a brief novel exploration unable to form memory of habituation; and (4) it increased in amnesic rats for spatial habituation. Taken as a whole, our results suggest that the elevated pCREB level after a single open field exploration is not associated with the memory formation of habituation. It is indeed associated with the detection of a novel environment.

Behavioural changes after an acute stress: stressor and test types influences

Behavioural consequences of different acute stressors (30 min of restraint, 20 min of forced swim stress, 15 min of inescapable footshocks) applied at the beginning of the active period were assessed in using two behavioural tests: a 20 min light extinction test 24 h after the stressor exposure in order to explore the psychomotor ability and a 10 min open field session within the dark period 48 h after the stressor exposure to estimate the emotional status and the locomotor activity of the rat. Different behavioural responses were observed depending on the nature of the applied stressor. In the light extinction test, the footshock-stressed rats developed a very low activity independent on light conditions whereas the rats submitted to forced swim and restraint exhibited an activity level depending on the strain. Moreover, restrained rats had a higher transient activity than forced swim rats under light condition. In the open field test, none of the stressed rats did develop differences in behaviour. The efficacy of a 24 h recovery period on the behavioural response to an acute stressor exposure depends on the intensity of the applied stressor and the behavioural demands.

EFFECTS OF SCORPION Tityus serrulatus VENOM TOXIN TS-8F ON RAT LEARNING AND MEMORY

Scorpion venom neurotoxins are responsible for toxicity and pharmacological effects. They are active in sodium and potassium channels leading to an increase in the release of neurotransmitters, such as glutamate. Glutamate is found in large quantities in the hippocampus (HPC) and is involved in the long-term potentiation (LTP) induction. The HPC is known to be related to certain kinds of memory. The aim of this study is to evaluate the effects of Tityus serrulatus TS-8F toxin on rat behavior with emphasis on learning and memory. We analyzed the effects of different doses of TS-8F on rat behavior in home cages, open-field (habituation), inhibitory avoidance, T-maze, and hippocampus morphology. In the first two experiments, 0.05µg/animal dose of TS-8F did not cause convulsion but led to a decrease in locomotion (LO) frequency in the open-field first session. During the second session, rats receiving 0.03µg/animal TS-8F showed a decrease in LO and rearing frequency (RE); controls only showed decreased LO; and those receiving 0.05µg/animal showed no significant changes. In inhibitory avoidance, T-maze, and HPC morphology experiments no significant differences were observed. It is concluded that TS-8F may exert some influence in rat learning and memory and seems to be useful as a pharmacological tool. Further research is required to elucidate all possible uses of this toxin.

Social attraction between rats in open field: long-term consequences of kindled seizures

Kindling of the amygdaloid complex in rats results in an enhanced emotionality frequently expressed by an elevated anxiety and defensive attitude toward other animals. Defensive attitude may have important consequences in social context and if tested in a large space it may eventually lead to social withdrawal. To test this hypothesis, rats were subjected to daily kindling sessions and their behavior was compared to implanted-sham and intact rats. Blood was collected after selected kindling trials for assessment of corticosterone response. Behavioral tests started 1 month after the last kindling trial and consisted of two open field sessions. A solitary rat was tested in the 1st session and pair of rats was tested simultaneously in the second session. Results showed that kindling changed the balance between exploration and occupation of a home base (HB) in the open field, in favor of higher preference of the home base occupancy. These results were apparent only during the social session leading to the conclusion that rats preferred to stay in the home base to maximize the proximity to a partner rat. This was supported by the observation that by increasing the occupancy of the HB, the kindled rats accomplished the longest concurrent presence with the partner rat in the common HB. We discuss the level of inter-rats aggression as a factor defining whether the anxious kindled rats will respond with increased or decreased social attraction in the open field test.

Pituitary–adrenal axis and behavioural responses of maternally deprived juvenile rats to the open field

Adult rats submitted to maternal deprivation (DEP) on post-natal day (pnd) 11 show smaller corticosterone (CORT) response to a saline injection than non-deprived (NDEP) rats, mainly at 30 days of age. In the present study we sought to investigate the pituitary–adrenal axis response of 30-day-old DEP rats to a 5-min open-field session, with lights and sound on. Hormone levels were assessed immediately or 20 min after the end of the stress, and were compared to basal levels. The immediate ACTH response of DEP females was the highest; this difference was no longer observed at 20 min, but hormone levels were still higher than basal. Both males and females showed an augmented CORT secretion immediately after the open field session, although only the response of NDEP females was higher than that of male counterparts. Moreover, DEP females showed a lower CORT response than their NDEP counterparts immediately after the stress. The CORT stress response remained equally elevated in males and females at the 20-min time point. Finally, DEP animals, regardless of the gender, ambulated more in the centre of the open field and displayed less grooming behaviour than NDEP pups, suggesting that DEP rats are less emotional than NDEP animals.

Characterization of postischemic behavioral deficits in gerbils with and without hypothermic neuroprotection

Five minutes of global ischemia in gerbil results in delayed hippocampal CA1 neuronal degeneration, which is accompanied by working memory impairments and hyperactivity in novel environments. In this study, postischemic activity was characterized in familiar and in novel environments to determine whether hyperactivity was due to impaired spatial habituation or another form of motor hyperactivity. This study also determined whether 6-h delayed hypothermia, which reduces CA1 neuronal injury, would attenuate functional impairments. Gerbils were subjected to 5 min of normothermic ischemia or sham operation 2 days following implantation of brain temperature probes. One of two ischemic groups was cooled (>48 h) starting at 6-h postischemia. Locomotor activity in a familiar cage was measured for 6 days while activity in three novel environments was intermittently measured on days 4, 5 and 6. Open field behavior and working memory in a T-maze were also assessed. Untreated ischemia caused marked hyperactivity in the familiar cage on day 1, which reverted to near-normal by day 2. Nonetheless, these gerbils showed hyperactivity during novel environment sessions on days 4–6. This maze behavior, which predicted hippocampal CA1 injury, was not due to different habituation rates nor baseline hyperactivity. Conversely, open field sessions on day 8 revealed ischemic habituation rate deficits. Ischemia also impaired working memory in the T-maze. Delayed hypothermia, which reduced neuronal loss in the CA1 sector to 12% from 81%, reduced all functional impairments. Ischemic gerbils quickly developed spontaneous locomotion hyperactivity that returned to near-normal after 1 day. This motor hyperactivity did not explain the elevated activity found with delayed testing in novel environments. Regardless, only the open field test on day 8 revealed a habituation-like deficit.

Locomotor activity and defecation of rats observed alone and in pairs in repeated open-field sessions.

Several experiments with independent groups have shown social effects on open-field defecation and locomotor activity in male rats. In this experiment these social effects were studied with a different methodological approach, namely, with repeated measurements. One group of 8 animals was tested always alone in an open field over 10 trials on successive days. The second group of 16 animals was also tested alone on Days 1 to 4 and on Day 9, while they were placed in the open field with a conspecific on Days 5 to 8 and again on Day 10. There was markedly reduced defecation and enhanced locomotion with the conspecific present, while with the absence of the conspecific on Day 9 the scores again reached the level of the rats always tested alone. Therefore, the social effects on defecation and locomotion are very robust phenomena which can also be shown with dependent measurements.

Within‐session behavioral decrement of atypical antipsychotics: Role of novelty

In order to gain a better understanding of the characteristics of antipsychotic-induced within-session decrements in unconditioned behavioral responses of mice, and whether they are sensitive to novel environmental stimuli, we studied the acute effects of haloperidol and atypical antipsychotic drugs (sulpiride, thioridazine, clozapine, and remoxipride) in familiar and novel open-field conditions in mice. The results show that familiarized controls and antipsychotic-treated groups had a progressive reduction in ambulation and rearing during the 10-minute open-field session. By manipulating the configuration of the open-field situation, familiarized controls as well as mice treated with typical or atypical antipsychotic drugs were able to exhibit an enhanced response to the presentation of novel stimuli. It may be noted that both the maintenance and the initiation of ambulation were affected by antipsychotic treatment. Furthermore, when comparing novel versus familiar groups during the 10-minute session, the increase in ambulation induced by atypical antipsychotic treatment was maintained longer (6–8 minutes) than that induced by haloperidol (4 minutes). In summary, these findings show that an important feature in the reinstatement of both typical and atypical antipsychotic-induced behavioral decrement may be a change in the stimulus conditions. Drug Dev. Res. 42:71–75, 1997. © 1997 Wiley-Liss, Inc.

Within-session behavioral decrement of atypical antipsychotics: Role of novelty

In order to gain a better understanding of the characteristics of antipsychotic-induced within-session decrements in unconditioned behavioral responses of mice, and whether they are sensitive to novel environmental stimuli, we studied the acute effects of haloperidol and atypical antipsychotic drugs (sulpiride, thioridazine, clozapine, and remoxipride) in familiar and novel open-field conditions in mice. The results show that familiarized controls and antipsychotic-treated groups had a progressive reduction in ambulation and rearing during the 10-minute open-field session. By manipulating the configuration of the open-field situation, familiarized controls as well as mice treated with typical or atypical antipsychotic drugs were able to exhibit an enhanced response to the presentation of novel stimuli. It may be noted that both the maintenance and the initiation of ambulation were affected by antipsychotic treatment. Furthermore, when comparing novel versus familiar groups during the 10-minute session, the increase in ambulation induced by atypical antipsychotic treatment was maintained longer (6-8 minutes) than that induced by haloperidol (4 minutes). In summary, these findings show that an important feature in the reinstatement of both typical and atypical antipsychotic-induced behavioral decrement may be a change in the stimulus conditions.

Effects of Postnatal Handling of Rats on Emotional, HPA-Axis, and Prolactin Reactivity to Novelty and Conflict

The present studies evaluated whether or not postnatal handling (PH) (administered during the first 21 days of life) could enduringly improve coping behavior with novel and/or conflict situations. To this purpose, different groups of naive male rats (control and PH-treated) were submitted in separate experiments to 1 of the 3 following situations: an emotional reactivity test (in 4-month-old animals), an open-field session followed by endocrine measurements (in 7-month-old animals) and a punished drinking test (in 11-month-old animals). PH effects were significant in the 3 situations: handled animals were less resistant to capture or to the handling manouvers involved in the emotional reactivity test; the hormonal responses (corticosterone, prolactin, and ACTH changes) during and after an open-field stress were less intense, and PH effects lasted up to 11 months in the punished drinking test, as measured by a higher number of punished responses and less time spent freezing by handled animals during the punished period. The results are discussed in relation to previous evidence showing a long-lasting reduction of fearfulness in rats due to postnatal handling.

Behavioural effects of chronic administration of nimodipine in grouped or individually housed rats

1. 1. Behavioural experiments were carried out on grouped or individually housed rats, which assumed a daily dose of nimodipine (around 30 mg/kg/day). 2. 2. Two operant tests plus an open field session were made. In the “periodic conditioning” test, the schedule of reinforcement was changed from a fixed ratio to a fixed interval schedule. In the “reversal” test the contingency for food delivery was switched four times from one lever to the other in a two lever Skinner box. 3. 3. In the “periodic conditioning” test, nimodipine treatment did not cause significant modifications in grouped rats. Isolated controls showed a depressed performance, which was overcome by nimodipine treatment. 4. 4. In the “reversal” test nimodipine treatment seemed to improve the cognitive performances of grouped and isolated rats. No differences were found between experimental groups in “open field” test.