Effects of long-term individual housing of middle-aged female Octodon degus on spatial learning and memory in the Barnes maze task.

Introduction: Prolonged social isolation is a form of passive chronic stress that has consequences on human and animal behavior. The present study was undertaken to elucidate whether the long-term isolation would precipitate age-related changes in anxiety and spatial learning and memory in degus. Methods: We investigated the effects of long-term social isolation on anxiety levels in the light-dark test, and spatial orientation abilities in the Barnes maze. Middle-aged female Octodon degus were allocated to either group-housed (3 animals per cage) or individually-housed for 5 months. Results: Under this experimental condition, there were no significant group differences in the anxiety level tested in the light-dark test and in the motivation to escape from the Barnes maze. There were no significant differences in cortisol levels between individually- and group-housed animals. On the last acquisition training day of spatial learning, individually- housed animals had a significantly higher number of correct responses and a smaller number of reference and working memory errors than the group-housed animals. In addition, isolated animals showed a tendency for reference and working memory impairment on the retention trial, while group-housed degus showed improvement in these parameters. Discussion and conclusion: The present study indicates that prolonged social isolation during adulthood in female degus has a dual effect on spatial orientation. Specifically, it results in a significant improvement in acquisition skills but a slight impairment in memory retention. The obtained cognitive changes were not accompanied by modification in anxiety and cortisol levels.

Rats conserve passive avoidance retention level throughout the light phase of diurnal cycle.

Emotions and memory formation are sensible to circadian rhythm. Here we study whether the time of day during the light phase of the diurnal cycle affects emotional memory in male Wistar rats using the passive avoidance (PA) test. Experiments were conducted at the beginning of Zeitgeber time (ZT) (ZT0.5-2), mid-time (ZT5-6.5), and end (ZT10.5-12) of the light period. Our results suggest that time of day has no impact on emotional response during acquisition trials, but slightly influences cognitive response during the 24-hour retention trial. Retention response was highest for ZT5-6.5, followed by ZT0.5-2, and lowest for ZT10.5-12.

Intracranial pressure analysis software: A mapping study and proposal.

Introduction Intracranial pressure (ICP) monitoring and analysis are techniques that are, each year, applied to millions of patients with pathologies with million of patients annually. The detection of the so called A and B-waves, and the analysis of subtle changes in C-waves, which are present in ICP waveform, may indicate decreased intracranial compliance, and may improve the clinical outcome. Despite the advances in the field of computerized data analysis, the visual screening of ICP continues to be the means principally employed to detect these waves. To the best of our knowledge, no review study has addressed automated ICP analysis in sufficient detail and a need to research the state of the art of ICP analysis has, therefore, been identified. Methodology This paper presents a systematic mapping study to provide answers to 7 research questions: publication time, venue and source trends, medical tasks undertaken, research methods used, computational systems developed, validation methodology, tools and systems employed for evaluation and research problems identified. An ICP software prototype is presented and evaluated as a consequence of the results. Results A total of 23 papers, published between 1990 and 2020, were selected from 6 online databases. After analyzing these papers, the following information was obtained: diagnosis and monitoring medical tasks were addressed to the same extent, and the main research method used was evaluation research. Several computational systems were identified in the papers, the main one being image classification, while the main analysis objective was single pulse analysis. Correlation with expert analysis was the most frequent validation method, and few of the papers stated the use of a published dataset. Few authors referred to the tools used to build or evaluate the proposed solutions. The most frequent research problem was the need for new analysis methods. These results have inspired us to propose a software prototype with which provide an automated solution that integrates ICP analysis and monitoring techniques. Conclusions The papers in this study were selected and classified with regard to ICP automated analysis methods. Several research gaps were identified, which the authors of this study have employed as a based on which to recommend future work. Furthermore, this study has identified the need for an empirical comparison between methods, which will require the use and development of certain standard metrics. An in-depth analysis conducted by means of systematic literature review is also required. The software prototype evaluation provided positive results, showing that the prototype may be a reliable system for A-wave detection.

Widespread Doublecortin Expression in the Cerebral Cortex of the Octodon degus.

It has been demonstrated that in adulthood rodents show newly born neurons in the subgranular layer (SGL) of the dentate gyrus (DG), and in the subventricular zone (SVZ). The neurons generated in the SVZ migrate through the rostral migratory stream (RMS) to the olfactory bulb. One of the markers of newly generated neurons is doublecortin (DCX). The degu similarly shows significant numbers of DCX-labeled neurons in the SGL, SVZ, and RMS. Further, most of the nuclei of these DCX-expressing neurons are also labeled by proliferating nuclear antigen (PCNA) and Ki67. Finally, whereas in rats and mice DCX-labeled neurons are predominantly present in the SGL and SVZ, with only a few DCX neurons present in piriform cortex, the degu also shows significant numbers of DCX expressing neurons in areas outside of SVZ, DG, and PC. Many areas of neocortex in degu demonstrate DCX-labeled neurons in layer II, and most of these neurons are found in the limbic cortices. The DCX-labeled cells do not stain with NeuN, indicating they are immature neurons.

Dopaminergic Modulation of Forced Running Performance in Adolescent Rats: Role of Striatal D1 and Extra-striatal D2 Dopamine Receptors.

Improving exercise capacity during adolescence impacts positively on cognitive and motor functions. However, the neural mechanisms contributing to enhance physical performance during this sensitive period remain poorly understood. Such knowledge could help to optimize exercise programs and promote a healthy physical and cognitive development in youth athletes. The central dopamine system is of great interest because of its role in regulating motor behavior through the activation of D1 and D2 receptors. Thus, the aim of the present study is to determine whether D1 or D2 receptor signaling contributes to modulate the exercise capacity during adolescence and if this modulation takes place through the striatum. To test this, we used a rodent model of forced running wheel that we implemented recently to assess the exercise capacity. Briefly, rats were exposed to an 8-day period of habituation in the running wheel before assessing their locomotor performance in response to an incremental exercise test, in which the speed was gradually increased until exhaustion. We found that systemic administration of D1-like (SCH23390) and/or D2-like (raclopride) receptor antagonists prior to the incremental test reduced the duration of forced running in a dose-dependent manner. Similarly, locomotor activity in the open field was decreased by the dopamine antagonists. Interestingly, this was not the case following intrastriatal infusion of an effective dose of SCH23390, which decreased motor performance during the incremental test without disrupting the behavioral response in the open field. Surprisingly, intrastriatal delivery of raclopride failed to impact the duration of forced running. Altogether, these results indicate that the level of locomotor response to incremental loads of forced running in adolescent rats is dopamine dependent and mechanistically linked to the activation of striatal D1 and extra-striatal D2 receptors.

The diurnal variation of open-field habituation in rats.

The present study aimed to establish the effect of time of the day on habituation in the open-field test, one of the most elementary forms of non-associative hippocampal-dependent learning. Open-field test was performed in young adult male Wistar rats at the beginning (08:30-10:00 h; defined as Zeitgeber time (ZT) ZT0.5-2), mid-time (13:00-14:30 h, ZT5-6.5) and at the end (18:30-20:00 h, ZT10.5-12) of the light period. Our results revealed that in the acquisition trial there were no significant differences among the six parameters recorded through tested periods. In contrast, the level of habituation in the ambulation and rearing rose as followed: ZT0.5-2 < ZT10.5-12 < ZT5-6.5. In both trials, the principal component analysis highlights two components: component 1 was mainly loaded by ambulation in the outer and inner area, rearing and freezing behaviors, whereas component 2 was mostly loaded on grooming activity and defecation. The correlation between parameters varied across the period of day and trial. Animals that expressed a higher level of grooming, defecation (ZT5-6.5) and freezing behavior (ZT0.5-2 and ZT5-6.5) at acquisition trial habituated better on those parameters on the retention trial. In conclusion, habituation outcomes to the open-field test and correlation between tested parameters highly depend on daytime.

Hypothalamic Crh/Avp, Plasmatic Glucose and Lactate Remain Unchanged During Habituation to Forced Exercise.

It has been demonstrated that physical activity contributes to a healthier life. However, there is a knowledge gap regarding the neural mechanisms producing these effects. One of the keystones to deal with this problem is to use training programs with equal loads of physical activity. However, irregular motor and stress responses have been found in murine exercise models. Habituation to forced exercise facilitates a complete response to a training program in all rodents, reaching the same load of physical activity among animals. Here, it was evaluated if glucose and lactate - which are stress biomarkers - are increased during the habituation to exercise. Sprague-Dawley rats received an 8-days habituation protocol with progressive increments of time and speed of running. Then, experimental and control (non-habituated) rats were subjected to an incremental test. Blood samples were obtained to determine plasmatic glucose and lactate levels before, immediately after and 30 min after each session of training. Crh and Avp mRNA expression was determined by two-step qPCR. Our results revealed that glucose and lactate levels are not increased during the habituation period and tend to decrease toward the end of the protocol. Also, Crh and Avp were not chronically activated by the habituation program. Lactate and glucose, determined after the incremental test, were higher in control rats without previous contact with the wheel, compared with habituated and wheel control rats. These results suggest that the implementation of an adaptive phase prior to forced exercise programs might avoid non-specific stress responses.

Sex and Time-of-Day Impact on Anxiety and Passive Avoidance Memory Strategies in Mice.

In humans, anxiety and cognitive processes are age, gender, and time of day dependent. The purpose of the present study was to assess whether the time of day and sex have an influence on anxiety and emotional memory in adult mice. Light-dark and passive avoidance (PA) tests were performed at the beginning and at the end of the light cycle, defined as Zeitgeber time (ZT) ZT0-2.5 and ZT9.5-12, respectively. A baseline difference in anxiety was not found, but on the 24 h retention trial of the PA test, females presented longer latencies to enter into the dark compartment at the ZT0-2.5 time point of the day. The data from the second test day (PA reversal trial) indicated that some animals associated the dark compartment with an aversive stimulus (shock), while others associated the aversive stimulus with crossing from one compartment to another. At the ZT9.5-12, female mice mainly related the aversive stimulus to transferring from one compartment to another, while male mice associated darkness with the aversive stimulus. There was a negative correlation between the frequency of light-dark transitions in the light-dark test and the PA latency on the 24 h retention trial in males tested at ZT0-2.5. The PA latency on the reversal and 24 h retention trials negatively correlated with a risk assessment behavior in male mice tested on ZT0-2.5 and ZT9.5-12, respectively. In conclusion, our data reveal that the impact of motor activity and risk assessment behavior on PA memory formation and applied behavioral strategies are time of day and sex dependent.

Verapamil and Alzheimer's Disease: Past, Present, and Future.

Verapamil is a phenylalkylamine class calcium channel blocker that for half a century has been used for the treatment of cardiovascular diseases. Nowadays, verapamil is also considered as a drug option for the treatment of several neurological and psychiatric disorders, such as cluster headache, bipolar disorders, epilepsy, and neurodegenerative diseases. Here, we review insights into the potential preventive and therapeutic role of verapamil on Alzheimer's disease (AD) based on limited experimental and clinical data. Pharmacological studies have shown that verapamil has a wide therapeutic spectrum, including antihypertensive, anti-inflammatory, and antioxidative effects, regulation of the blood-brain barrier function, due to its effect on P-glycoprotein, as well as adjustment of cellular calcium homeostasis, which may result in the delay of AD onset or ameliorate the symptoms of patients. However, the majority of the AD individuals are on polypharmacotherapy, and the interactions between verapamil and other drugs need to be considered. Therefore, for an appropriate and successful AD treatment, a personalized approach is more than necessary. A well-known narrow pharmacological window of verapamil efficacy may hinder this approach. It is therefore important to note that the verapamil efficacy may be conditioned by different factors. The onset, grade, and brain distribution of AD pathological hallmarks, the time-sequential appearances of AD-related cognitive and behavioral dysfunction, the chronobiologic and gender impact on calcium homeostasis and AD pathogenesis may somehow be influencing that success. In the future, such insights will be crucial for testing the validity of verapamil treatment on animal models of AD and clinical approaches.

Time-of-Day and Age Impact on Memory in Elevated Plus-Maze Test in Rats.

The purpose of the present study was to establish the effect of daytime and aging on memory in rats in the Elevated Plus-Maze (EPM) test. Young (2-months) and aged (18-months) male Wistar rats were exposed to the EPM test, at the beginning, mid-time or at the end of the light period. On the acquisition trial, the animals were placed individually at the end of one of the open arms of the EPM and the latency to enter in the enclosed arms was registered (cut-off time 60 s). The test was repeated 24 h later on. A longer latency period to reach the enclosed arm indicated poor retention compared to significantly shorter latencies. There were no significant differences between groups on the acquisition trial. In all tested periods, the latency time on the 24 h retention trial was significantly shorter in the young rats compared to the old ones. Furthermore, in the early and mid-time period of the light period, the young rats showed significantly decreased transfer latency (TL) time on the 24 h retention trial in comparison with the acquisition trial. In the aged rats, the TL time on the 24 h retention trial was significantly longer at the end of the light period, in comparison to the two other testing periods. In conclusion, aging significantly affects memory and the more critical period for memory process in both young and old animals, particularly at the end of the light period of the circadian cycle.

Verapamil Blocks Scopolamine Enhancement Effect on Memory Consolidation in Passive Avoidance Task in Rats.

Our recent data have indicated that scopolamine, a non-selective muscarinic receptor antagonist, improves memory consolidation, in a passive avoidance task, tested in rats. It has been found that verapamil, a phenylalkylamine class of the L-type voltage-dependent calcium channel antagonist, inhibits [3H] N-methyl scopolamine binding to M1 muscarinic receptors. However, there are no data about the effect of verapamil on memory consolidation in the passive avoidance task, in rats. The purpose of the present study was to examine the effects of verapamil (0.5, 1.0, 2.5, 5.0, 10, or 20 mg/kg i.p.) as well as the interaction between scopolamine and verapamil on memory consolidation in the step-through passive avoidance task, in Wistar rats. Our results showed that verapamil (1.0 and 2.5 mg/kg) administered immediately after the acquisition task significantly increased the latency of the passive avoidance response, on the 48 h retested trial, improving memory consolidation. On the other hand, verapamil in a dose of 5 mg/kg, that per se does not affect memory consolidation, significantly reversed the memory consolidation improvement induced by scopolamine (1 mg/kg, i.p., administered immediately after verapamil treatment) but did not change the passive avoidance response in rats treated by an ineffective dose of scopolamine (30 mg/kg). In conclusion, the present data suggest that (1) the post-training administration of verapamil, dose-dependently, improves the passive avoidance response; (2) verapamil, in ineffective dose, abolished the improvement of memory consolidation effect of scopolamine; and (3) exists interaction between cholinergic muscarinic receptors and calcium homeostasis-related mechanisms in the consolidation of emotional memory.

Verapamil Parameter- and Dose-Dependently Impairs Memory Consolidation in Open Field Habituation Task in Rats.

The purpose of the present study was to examine the effects of the phenylalkylamine class of the L-type voltage-dependent calcium channel antagonist, verapamil (1.0, 2.5, 5.0, or 10 mg/kg i.p.), administered immediately after the acquisition task, on memory consolidation of the open field habituation task, in male Wistar rats. On the 48 h retested trial, all tested parameters (ambulation in the side wall and in the central areas, number of rearing, time spent grooming and defecation rate) significantly decreased in the saline treated animals. A significant decrease of rearing was observed in all verapamil treated groups. On the retention day, the ambulation in the side wall and central areas significantly decreased in the animals treated with 1 mg/kg and 10 mg/kg of verapamil, while the time spent grooming and the defecation rate significantly decreased only in the group treated with 1 mg/kg of verapamil. According to the change ratio scores that correct the individual behavioral baseline differences during initial and final sessions, habituation deficit was found in animals treated with verapamil as follows: ambulation along the side wall area (1, 2.5, and 5 mg/kg), number of rearing (all used dose) and time spent grooming (2.5, 5, and 10 mg/kg). In conclusion, the present data suggest that the post-training administration of verapamil, parameter- and dose-dependently, impairs the habituation to a novel environment.

Time course of scopolamine effect on memory consolidation and forgetting in rats.

The effect of scopolamine on the consolidation and forgetting of emotional memory has not been completely elucidated yet. The aim of the present study was to investigate the time course of scopolamine effect on consolidation and forgetting of passive avoidance response. In a first experiment of the present study, we tested the effect of scopolamine (1mg/kg, i.p., immediately after acquisition), on 24h and 48h retention performance of the step-through passive avoidance task, in adult male Wistar rats. On the 24h retested trial, the latency of the passive avoidance response was significantly lower, while on the 48h retested trial it was significantly higher in scopolamine than in the saline-treated group. In a second experiment, we assessed the 24h time course of scopolamine (1mg/kg) effect on memory consolidation in passive avoidance task. We found that scopolamine administration only within the first six and half hours after acquisition improved memory consolidation in 48h retention performance. Finally, a third experiment was performed on the saline- and scopolamine-treated rats (given immediately after acquisition) that on the 48h retention test did not step through into the dark compartment during the cut-off time. These animals were retested weekly for up to first three months, and after that, every three months until the end of experiment (i.e., 15 months after acquisition). The passive avoidance response in the saline treated group lasted up to 6 weeks after acquisition, while in the scopolamine treated group 50% of animals conserved the initial level of passive avoidance response until the experiment end point. In conclusion, the present data suggest that (1) improving or impairment effect of scopolamine given in post-training periods depends on delay of retention trial, (2) memory consolidation process could be modify by scopolamine within first six and half hours after training and (3) scopolamine could delay forgetting of emotional memory.

Post-training scopolamine treatment induced maladaptive behavior in open field habituation task in rats.

The effects of scopolamine on memory consolidation are controversial and depend on several factors (i.e. site of administration, time of administration and testing, dose, cognitive task, experimental protocol, specie, strain, etc.). Generally, the range dose of systemic administered scopolamine, used in memory consolidation studies, has varied from 0.05 to 50 mg/kg. However, according to the literature, the most frequently used doses of scopolamine efficient on memory consolidation, are 1 and 30 mg/kg, low and high doses, respectively. In open field habituation studies only lower doses of scopolamine were used to test memory consolidation. Therefore, in the present study we compared the effects of low (1 mg/kg) and high (30 mg/kg) scopolamine dose, on the open field habituation task, in male Wistar rats. Scopolamine was administered immediately after the acquisition task and animals were retested 48 h later on. On the retested day, the ambulation and rearing in the open field decreased in the same manner in all tested groups. In saline- and 1 mg/kg scopolamine-treated animals, the time spent in grooming significantly decreased in the habituation task, while the same parameter significantly increased in animals treated with 30 mg/kg of scopolamine. The defecation rate significantly decreased (control group), maintained (1 mg/kg of scopolamine treated animals) or significantly increased (30 mg/kg of scopolamine treated group) on retention test. In conclusion, the present data suggest that post-training scopolamine administration does not affect locomotion neither exploration in the habituation to a novel environment, but increases defecation and grooming, two behaviours associated with fearful and stressful situations.

The flavonoid apigenin delays forgetting of passive avoidance conditioning in rats.

The present experiments were performed to study the effect of the flavonoid apigenin (20 mg/kg intraperitoneally (i.p.), 1 h before acquisition), on 24 h retention performance and forgetting of a step-through passive avoidance task, in young male Wistar rats. There were no differences between saline- and apigenin-treated groups in the 24 h retention trial. Furthermore, apigenin did not prevent the amnesia induced by scopolamine (1mg/kg, i.p., 30 min before the acquisition). The saline- and apigenin-treated rats that did not step through into the dark compartment during the cut-off time (540 s) were retested weekly for up to eight weeks. In the saline treated group, the first significant decline in passive avoidance response was observed at four weeks, and complete memory loss was found five weeks after the acquisition of the passive avoidance task. At the end of the experimental period, 60% of the animals treated with apigenin still did not step through. These data suggest that 1) apigenin delays the long-term forgetting but did not modulate the 24 h retention of fear memory and 2) the obtained beneficial effect of apigenin on the passive avoidance conditioning is mediated by mechanisms that do not implicate its action on the muscarinic cholinergic system.

Long-term social isolation in the adulthood results in CA1 shrinkage and cognitive impairment.

Social isolation in adulthood is a psychosocial stressor that can result in endocrinological and behavioral alterations in different species. In rodents, controversial results have been obtained in fear conditioning after social isolation at adulthood, while neural substrates underlying these differences are largely unknown. Neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) are prominent modulators of synaptic plasticity underlying memory processes in many tasks, including fear conditioning. In this study, we used adult female Octodon degus to investigate the effects of long-term social isolation on contextual and cued fear conditioning, and the possible modulation of the synaptic levels of NCAM and PSA-NCAM in the hippocampus. After 6½ months of social isolation, adult female degus showed a normal auditory-cued fear memory, but a deficit in contextual fear memory, a hippocampal dependent task. Subsequently, we observed reduced hippocampal synaptic levels of PSA-NCAM in isolated compared to grouped-housed female degus. No significant differences were found between experimental groups in hippocampal levels of the three main isoforms of NCAM (NCAM180, NCAM140 and NCAM120). Interestingly, social isolation reduced the volume of the hippocampal CA1 subfield, without affecting the volume of the CA3 subregion or the total hippocampus. Moreover, attenuated body weight gain and reduced number of granulocytes were detected in isolated animals. Our findings indicate for the first time, that long-term social isolation of adult female animals induces a specific shrinkage of CA1 and a decrease in synaptic levels of PSA-NCAM in the hippocampus. These effects may be related to the deficit in contextual fear memory observed in isolated female degus.

Circadian system functionality, hippocampal oxidative stress, and spatial memory in the APPswe/PS1dE9 transgenic model of Alzheimer disease: effects of melatonin or ramelteon.

Alzheimer disease (AD) is a neurodegenerative disorder that primarily causes ß-amyloid accumulation in the brain, resulting in cognitive and behavioral deficits. AD patients, however, also suffer from severe circadian rhythm disruptions, and the underlying causes are still not fully known. Patients with AD show reduced systemic melatonin levels. This may contribute to their symptoms, since melatonin is an effective chronobiotic and antioxidant with neuroprotective properties. Here, the authors critically assessed the effects of long-term melatonin treatment on circadian system function, hippocampal oxidative stress, and spatial memory performance in the APPswe/PS1 double transgenic (Tg) mouse model of AD. To test if melatonin MT1/MT2 receptor activation, alone, was involved, the authors chronically treated some mice with the selective MT1/MT2 receptor agonist ramelteon. The results indicate that many of the circadian and behavioral parameters measured, including oxidative stress markers, were not significantly affected in these AD mice. During the day, though, Tg controls (Tg-CON) showed significantly higher mean activity and body temperature (BT) than wild-type (WT) mice. Overall, BT rhythm amplitude was significantly lower in Tg than in WT mice. Although melatonin treatment had no effect, ramelteon significantly reduced the amplitude of the BT rhythm in Tg mice. Towards the end of the experiment, Tg mice treated with ramelteon (Tg-RAM) showed significantly higher circadian rhythm fragmentation than Tg-CON and reduced circadian BT rhythm strength. The free-running period (τ) for the BT and locomotor activity (LA) rhythms of Tg-CON was <24 h. Whereas melatonin maintained τ at 24 h for BT and LA in both genotypes, ramelteon treatment had no effect. In the behavioral tests, the number of approaches and time spent exploring novel objects were significantly higher in Tg-CON than WT controls. Brain tissue analysis revealed significant reduction in hippocampal protein oxidation in Tg-MEL and Tg-RAM compared with Tg-CON animals. These results suggest that not all aspects of the circadian system are affected in the APPswe/PS1 mice. Therefore, care should be taken when extending the results obtained in Tg mice to develop new therapies in humans. This study also revealed the complexity in the therapeutic actions of melatonin and ramelteon in this mouse model of AD.

Age-related brain pathology in Octodon degu: blood vessel, white matter and Alzheimer-like pathology.

Recently it has been shown that over 3-year-old wild-type South American rodents, Octodon degus, the "common degu" or degu, of their own accord develop Alzheimer's disease neuropathological hallmarks: amyloid-ß-peptide depositions and accumulation of tau-protein. Here we analyzed brains of 1-, 3- and 6-year-old degu's, bred in standard animal facilities. Significant amounts of Aß and tau deposits are present in the hippocampal formation of 6-year-old O. degus, primarily in the white matter, but these hippocampal Aß and tau deposits are not present in younger ones. In contrast, significant Aß deposits in blood vessel walls are already found in 3-year-old animals. The tau deposits in the hippocampal formation coincide with a significant decrease in staining for myelin in the same areas, indicating hippocampal disconnection and, likely, dysfunction. Our findings indicate that (1) cerebral amyloid angiopathy precedes brain parenchyma pathology in aged degu's and (2) the onset of disease seems to be delayed in the laboratory vs. wild-type degu's.

Barnes maze performance of Octodon degus is gender dependent.

Gender differences in spatial navigation have been widely reported in nocturnal rodent species. Here, for the first time we report gender differences in spatial learning and memory of Octodon degus, a long-lived diurnal hystricomorph rodent. In the present study, 16 months old male and female O. degus were tested in the 18-holes Barnes circular maze. The acquisition session consisted of four daily 4 min trials, during 10 days. Seven days later, the retention test was performed. To avoid the effect of hormonal fluctuation on spatial navigation, both the acquisition and the retention tests, were performed in 21-day regular cycling females in a period that corresponds to the diestrus phase of the estrus cycle. At the beginning of the acquisition, female degus were significantly slower than males to find the escape hole, but the situation reversed afterwards. Moreover, during the course of acquisition, females made significantly less reference memory errors, working memory errors as well as omission errors, than males. In both sexes, motivation and learning ceiling effects were reached at days 5-6 of the training. During the acquisition, females used more frequently a spatial strategy, while males preferably applied either serial, random or opposite strategies. The observed cognitive differences between male and female O. degus existed only during the acquisition period but not during the retention, indicating that acquisition and consolidation are differently influenced by gender.

Aging and time-of-day effects on anxiety in female Octodon degus.

Animal models of anxiety have usually employed nocturnal species (e.g. rats and mice), and the tests used have been almost exclusively performed during the diurnal phase (lights on). Here, for the first time, we tested anxiety in a diurnal rodent, Octodon degus, according to its age (23 versus 40 months of age) and the time of the day. We employed three anxiety tests: object recognition, open field and light-dark tests, which were applied in the morning, at mid-day and in the late afternoon, respectively. Adult animals spent more time exploring a new object than aged animals. Nevertheless, there were no differences in the frequency of object exploration or in the latency to the first object approach between the groups. In the open field test, adult animals spent more time exploring (ambulation and rearing) than aged ones. Although both groups exhibited similar frequencies in transition from the dark to the light box in the light-dark test, adult animals spent significantly more time in the light, and expressed less anxiety when making the decision to cross over from the dark into the light area. In conclusion, there were no differences in anxiety between adult and aged animals in the morning session, although adult animals were more attentive when exploring a new object. However, in the mid-day and afternoon testing sessions, aged animals were more anxious than adults.