Cognitive and noncognitive processes involved in selective object exploration: comparison between young adult and old rats.

The age effects on locomotor activity, object-oriented exploration, habituation, and response to a spatial change were studied in young adult and old rats using an object exploration test. In this test the spatial response was evaluated by the renewal of exploration of a familiar object after its repositioning. The specificity of the spatial response was determined by comparison with control animals not submitted to a spatial change. Male Wistar rats 6 and 24 months old were used. Results showed a significant decrement in locomotor activity, object exploration, and spatial reactivity in old rats. The habituation curve and the reactivity to a new object were preserved. Detail analyses suggest that the spatial deficit of old rats is due to an incapacity to detect the spatial change and not to their poor locomotor or exploratory activity. These results corroborate those obtained in spatial orientation tasks and support the idea that the lack of spatial response observed in old animals is more related to cognitive impairments than to other factors such as sensory, motor, or motivational differences.     

Long-term object location memory in rats: Effects of sample phase and delay length in spontaneous place recognition test

This study investigates the effects of sample phase and delay length on discrimination performance in the spontaneous place recognition (SPR) test in rats. Rats were allowed to explore an arena where two identical objects were presented for 5–20 min (sample phase). After a delay interval, rats were placed again in the same arena but one of the two objects was moved to a novel place (test phase). Results showed that when the sample phase was as long as 20 min, rats preferentially explored the moved object during the test phase even after a 6–24 h delay was interposed. Further sequential and cumulative analyses of the test phase revealed that the preference for the object in a novel place was evident in the first and 2nd min of the test phase in rats with a longer sample phase duration. Correlation analysis showed that locomotor activity and object exploration in the sample phase were not decisive factors in spatial memory performance. The present results demonstrate the importance of the sample phase exposure time and the test phase length.     

Ontogeny of spatial discrimination in mice: a longitudinal analysis in the modified open-field with objects

The present longitudinal study investigated the emergence of spatial discrimination and reaction to novelty in CD-1 mice, using a modified open-field test with four objects, a test in which responses to both spatial rearrangement of familiar objects and object novelty are assessed. Male and female mice were tested on postnatal days (pnd) 18, 28, 46 and 90. Locomotor activity was highest on pnd 90, whereas time spent on objects before rearrangement was highest on pnd 46. Eighteen-day old mice were unable to detect both object rearrangement and object novelty, suggesting immaturity in processing spatial information. On days 28 and 46 mice showed a clear response to object novelty, actively exploring the unfamiliar object placed in the arena, while at these ages object displacement elicited a generalized increase of exploration, not directed towards the displaced objects. A clear and selective response to object displacement emerged only at adulthood (day 90).     

Pattern separation deficits may contribute to age-associated recognition impairments

Normal aging is associated with impairments in stimulus recognition. In the current investigation, object recognition was tested in adult and aged rats with the standard spontaneous object recognition (SOR) task or two variants of this task. On the standard SOR task, adult rats showed an exploratory preference for the novel object over delays up to 24 h, whereas the aged rats only showed significant novelty discrimination at the 2-min delay. This age difference appeared to be because of the old rats behaving as if the novel object was familiar. To test this hypothesis directly, rats participated in a variant of the SOR task that allowed the exploration times between the object familiarization and the test phases to be compared, and this experiment confirmed that aged rats falsely "recognize" the novel object. A final control examined whether or not aged rats exhibited reduced motivation to explore objects. In this experiment, when the environmental context changed between familiarization and test, young and old rats failed to show an exploratory preference because both age groups spent more time exploring the familiar object. Together these findings support the view that age-related impairments in object recognition arise from old animals behaving as if novel objects are familiar, which is reminiscent of behavioral impairments in young rats with perirhinal cortical lesions. The current experiments thus suggest that alterations in the perirhinal cortex may be responsible for reducing aged animals' ability to distinguish new stimuli from ones that have been encountered previously.     

Similarities and differences in spatial learning and object recognition between young male C57Bl/6J mice and Sprague-Dawley rats

Mice and rats are often used interchangeably in neuroscience research. However, species differences in brain structure and connectivity exist within the medial temporal lobe circuits that contribute to learning and memory. The hippocampus in particular contributes to both spatial learning and recognition memory, but the extent to which rats and mice are comparable in these two cognitive domains remains unclear. To evaluate potential species differences in spatial memory and object recognition, young adult male Sprague-Dawley rats and male C57Bl/6J mice were tested in the water maze and novel object recognition tasks. Following six days of training, with four trials per day, there was no difference in the ability of rats and mice to learn the location of a hidden platform. However, rats performed better than mice on the probe trial, indicative of superior retention. In the novel object preference test, no species differences in recognition memory were detected, although rats spent more time exploring the arena and took longer to approach the objects. These observations suggest that while species differences in spatial memory retention are present, they do not correlate with differences in object recognition memory.     

Short-term memory, exploration and locomotor activity in aged rats

Behavioral profiles of young (3-6 months) and aged (24-27 months) rats were compared in three respects: (1) short-term memory, (2) exploration and (3) locomotor activity. Compared to young rats, aged rats were impaired in the 8-arm radial maze acquisition, but not in the delayed reinforced alternation acquisition. They had lower scores of spontaneous alternation, of exploration of a novel object and of a novel environment. Their exploratory activity was lower in a simple environment but similar in a complex environment. Their spontaneous locomotor activity was lower during the dark part of the cycle (8 p.m.-8 a.m.) but not different during the light part of the cycle (8 a.m.-8 p.m.). These results suggest that with respect to short-term memory and exploration, differences between aged and young rats may be influenced by a "complexity" factor and may be secondary to differences in motivation and reactions to novelty.     

Ontogeny of Rat Recognition Memory measured by the novel object recognition task

Detection of novelty is an essential component of recognition memory, which develops throughout cerebral maturation. To better understand the developmental aspects of this memory system, the novel object recognition task (NOR) was used with the immature rat and ontogenically profiled. It was hypothesized that object recognition would vary across development and be inferior to adult performance. The NOR design was made age‐appropriate by downsizing the testing objects and arena. Weanling (P20–23), juvenile (P29–40), and adult (P50+) rats were tested after 0.25, 1, 24, and 48 hr delays. Weanlings exhibited novel object recognition at 0.25 and 1 hr, while older animals showed a preference for the novel object out to 24 hr. These findings are consistent with previous research performed in humans and monkeys, as well as to studies using the NOR after medial temporal lobe damage in adult rats. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 672–678, 2009     

Excitotoxic lesions of the pre- and parasubiculum disrupt object recognition and spatial memory processes

Rats with bilateral ibotenic acid lesions centered on the pre- and parasubiculum and control rats were tested in a series of spatial memory and object recognition memory tasks. Lesioned rats were severely impaired relative to controls in both the reference and working memory versions of the water maze task and displayed a delay-dependent deficit in a delayed nonmatch to place procedure conducted in the T-maze. Lesioned rats also displayed reduced exploration in a novel environment, and performance was altered in an object recognition procedure as compared with the control group. These findings indicate that the pre- and parasubiculum plays an important role in the processing of both object recognition and spatial memory.     

Age-associated deficits in pattern separation functions of the perirhinal cortex: a cross-species consensus

Normal aging causes a decline in object recognition. Importantly, lesions of the perirhinal cortex produce similar deficits and also lead to object discrimination impairments when the test objects share common features, suggesting that the perirhinal cortex participates in perceptual discrimination. The current experiments investigated the ability of young and aged animals to distinguish between objects that shared features with tasks with limited mnemonic demands. In the first experiment, young and old rats performed a variant of the spontaneous object recognition task in which there was a minimal delay between the sample and the test phase. When the test objects did not share any features ("Easy" perceptual discrimination) both young and aged rats correctly identified the novel object. When the test objects contained overlapping features, however, only the young rats showed an exploratory preference for the novel object. In Experiment 2, young and aged monkeys were tested on an object discrimination task. When the object pairs were dissimilar, both the young and aged monkeys learned to select the rewarded object quickly. In contrast, when LEGOs? were used to create object pairs with overlapping features, the aged monkeys took significantly longer than did the young animals to learn to discriminate between the rewarded and the unrewarded object. Together, these data indicate that behaviors requiring the perirhinal cortex are disrupted in advanced age, and suggest that at least some of these impairments may be explained by changes in high-level perceptual processing in advanced age.     

Apoptosis and reduced microvascular density of the lamina propria during tooth eruption in rats

During tooth eruption, structural and functional changes must occur in the lamina propria to establish the eruptive pathway. In this study, we evaluate the structural changes that occur during lamina propria degradation and focus these efforts on apoptosis and microvascular density. Fragments of maxilla containing the first molars from 9‐, 11‐, 13‐ and 16‐day‐old rats were fixed, decalcified and embedded in paraffin. The immunohistochemical detection of vascular endothelial growth factor (VEGF), caspase‐3 and MAC387 (macrophage marker), and the TUNEL method were applied to the histological molar sections. The numerical density of TUNEL‐positive cells and VEGF‐positive blood vessel profiles were also obtained. Data were statistically evaluated using a one‐way anova with the post‐hoc Kruskal–Wallis or Tukey test and a significance level of P ≤ 0.05. Fragments of maxilla were embedded in Araldite for analysis under transmission electron microscopy (TEM). TUNEL‐positive structures, fibroblasts with strongly basophilic nuclei and macrophages were observed in the lamina propria at all ages. Using TEM, we identified processes of fibroblasts or macrophages surrounding partially apoptotic cells. We found a high number of apoptotic cells in 11‐, 13‐ and 16‐day‐old rats. We observed VEGF‐positive blood vessel profiles at all ages, but a significant decrease in the numerical density was found in 13‐ and 16‐day‐old rats compared with 9‐day‐old rats. Therefore, the establishment of the eruptive pathway during the mucosal penetration stage depends on cell death by apoptosis, the phagocytic activity of fibroblasts and macrophages, and a decrease in the microvasculature due to vascular cell death. These data point to the importance of vascular rearrangement and vascular neoformation during tooth eruption and the development of oral mucosa.     

Neural mechanisms of shifts of spatial attention induced by object words with spatial associations: an ERP study

We examined the effects of hippocampal (HPC) damage on odour recognition memory, using a novel odour recognition task that was adapted from the more common novel object recognition task. Three separate experiments were conducted. In Experiment 1, we tested rats in novel odour recognition across different retention intervals (i.e. 15 min, 24 h, 1 week, 5 weeks). Given a single acquisition session, rats’ performance deteriorated after 24 h, but given multiple acquisition sessions (i.e. four sessions over 2 days), rats were able to perform well after retention intervals up to 5 weeks. In Experiment 2, we examined the possible anterograde amnesic effects of HPC damage on novel odour recognition, finding that pre-training damage to the entire HPC failed to cause amnesia for retention delays extending up to 5 weeks. In Experiment 3, we examined whether post-training HPC damage would cause retrograde amnesia, but failed to find any evidence of an impairment. The combined results suggest that the neural network supporting odour recognition is independent of the HPC.     

High ethanol dose during early adolescence induces locomotor activation and increases subsequent ethanol intake during late adolescence

Adolescent initiation of ethanol consumption is associated with subsequent heightened probability of ethanol use disorders. The present study examined the relationship between motivational sensitivity to ethanol initiation in adolescent rats and later ethanol intake. Experiment 1 determined that ethanol induces locomotor activation shortly after administration but not if tested at a later post‐administration interval. In Experiment 2, adolescent rats were assessed for ethanol‐induced locomotor activation on postnatal Day 28. These animals were then evaluated for ethanol‐mediated conditioned taste aversion and underwent a 16‐day‐long ethanol intake protocol. Ethanol‐mediated aversive effects were unrelated to ethanol locomotor stimulation or subsequent ethanol consumption patterns. Ethanol intake during late adolescence was greatest in animals initiated to ethanol earliest at postnatal Day 28. Females that were more sensitive to ethanol's locomotor‐activating effects showed a transient increase in ethanol self‐administration. Blood ethanol concentrations during initiation were not related to ethanol‐induced locomotor activation. Adolescent rats appeared sensitive to the locomotor‐stimulatory effects of ethanol. Even brief ethanol exposure during adolescence may promote later ethanol intake. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 424–440, 2010.     

Age, sex and strain differences in activity and habituation in SHR and WKY rats

The highly inbred strain of Wistar-Kyoto spontaneously hypertensive rat (SHR) and its normotensive, genetic control (WKY) were examined with respect to strain differences in spontaneous activity scores in a novel environment (small activity cage) and in ability to habituate to that environment. These behaviors were examined in experimentally naive rats, 197 SHR and WKY, males and females, at varying ages from 4 to 56 weeks, in order to determine whether there are sex and age differences in addition to the well-known strain differences in these behaviors. Total activity scores, determined in a 15 min test in the activity cage, were higher in SHR than WKY rats; females were significantly more active than males in either strain, and activity scores varied significantly with age both within strains and between strains. Ability to habituate to the test cage was determined by repeating the 15 min activity test at hourly intervals for three additional trials on the same day. The results indicate that the SHR, males and females and at all ages tested, habituate poorly if at all to the test cage as compared with WKY rats. Moreover, despite the variability of baseline activity scores (first trial) observed across ages, sexes and strains, the habituation patterns of either strain remained relatively fixed throughout the first year of life.     

A behavioral characterization of the effects of food deprivation on food and nonfood object interaction: an investigation of the information-gathering functions of exploratory behavior

Previous research has shown that exploratory behavior serves not only to procure food, but also as a means of general information gathering. The purpose of this experiment was to investigate the function of exploratory behavior in rats by measuring behavior as they interacted with food and nonfood stimuli under different levels of food deprivation. Rats were food-deprived (0, 24, and 48 h), given free access to an open-field arena, and videotaped for a 20-min test session. The rats' behavior was assessed in a manner that isolated locomotor-, object-, and nonobject-related components. Deprivation did not affect locomotor activity levels; however, a decrease in rearing and propping against the test arena was shown. Rats distinguished between the food and nonfood objects because they attempted to ingest the food but not the nonfood object. Deprivation did result in increased contact with food objects; however, nonfood object interactions were maintained throughout the test session. These results suggest that exploratory behavior is separable from food seeking and functions in acquisition of information relating to multiple aspects of the environment.     

Effect of age on object exploration, habituation, and response to spatial and nonspatial change

To measure their ability to detect novel arrangements in a given environment, young (6 months old) and senescent (22-24 months old) male F344 rats were repeatedly exposed to a given spatial configuration of objects contained in an open field. After the rats were habituated to the novel environment (1 trial with no objects, followed by 3 trials with 5 salient objects), the spatial arrangement of the objects was modified (2 trials), and object novelty was tested (2 trials) by substituting a familiar object with a new one at the same location (nonspatial change). The results indicated that the senescent rats explored old objects less than young rats, particularly on Trial 2. On the 1st trial with displaced objects (Trial 5), the senescent rats explored the displaced objects less than the young rats. However, when a new object was placed in the field (Trials 7-8), there were no age differences in new object exploration. These results suggest that senescent rats have decrements in the ability to build spatial representations of the environment and to use this information to detect such changes, even though object recognition is not impaired with age.     

Emergence of the exploratory motive in rats

As infant rats approach weaning, they must overcome their infantile attraction to the home nest and prepare to leave its safety to forage for food. Although nutritive needs may help to motivate pups to make this bold move, a newly emerging exploratory motive also may play a role. Three experiments are reported here which examine age-related changes in the exploratory motive. In the first experiment, preferences for a novel side over a familiar side of a two-sided testing chamber were examined in postnatal Days 15 (P15), 17 (P17), 19 (P19), and 21 (P21) rat pups. Subjects did not prefer to explore the novel side until P19. In the same test, no preference for a novel object was observed at any of the ages tested, suggesting that this preference, which is expressed in adulthood, does not emerge until a later age; however, additional studies are needed to verify this. In the second experiment, P15 subjects demonstrated their ability to discriminate the two sides of the testing chamber in a novelty-induced locomotion test. In the third experiment, the presence of a home-nest-associated object was shown to inhibit exploration of novel context in P15, but not P21, subjects. These data suggest that home nest egression may be more the consequence of the declining attractiveness of the home nest than of a growing exploratory motive.     

Tyrosine administration to pregnant rats induces persistent behavioral modifications in the male offspring

Pregnant rats were given, by stomach intubation, 1-tyrosine (20 or 500 mg/kg), beginning on day 11 post-coitus. Tyrosine or saline solution administrations were continued on a once-daily basis until day 20 of gestation. When male offspring were seventy days old, the spontaneous locomotor activity, open field test, swim test and motor ability test were performed. The offspring treated with large tyrosine doses showed a marked increase in both spontaneous locomotor activity and open field locomotion as adults. However, activity in the swim test decreased. The number of defecation boluses produced in the open field test and the motor ability in the rotating rod test diminished. The behavior of the rats treated with small doses of tyrosine was similar, in all tests performed, to that of rats treated with saline solution. These findings strongly suggest that a large increase in diet tyrosine during pregnancy modifies the behavior of male offspring.     

Neonatal Exposure of Rats to Antidepressants Affects Behavioral Reactions to Novelty and Social Interactions in a Manner Analogous to Autistic Spectrum Disorders

We have demonstrated that neonatal exposure to selective serotonin reuptake inhibitors has lasting effects on behavior and serotonergic neurons in Long Evans rats. Hyperserotoninemia and altered sensory processing are reported in autistic spectrum disorders (ASD). We hypothesized that early life exposure to SSRIs alters sensory processing, disrupts responses to novelty, and impairs social interactions in a manner similar to that observed in ASD. Male and female Long‐Evans rat pups were administered citalopram, buproprion, fluoxetine, or saline from postnatal day (P) 8–21. Rats were tested for response to a novel tone before weaning (P25). Later, rats were tested 2× for response to a novel object (P39), and to a novel conspecific (P78, P101). In addition, rats were assessed for juvenile play behaviors (P32–P34) and later, we assessed sexual response to an estrus female in male rats (P153–184). Antidepressant exposure increased freezing after tone, diminished novel object exploration, and reduced conspecific interaction up to 3× compared to saline exposed rats. Juvenile play was profoundly reduced in antidepressant‐exposed males when compared to saline exposed groups. Exposure to the SSRIs, but not bupropion disrupted male sexual behaviors. Moreover, specific male responses to female proceptive behaviors were disrupted in SSRI, but not bupropion exposed rats. We conclude that neonatal exposure to antidepressants in rats results in sensory and social abnormalities that parallel many of those reported in ASD. Anat Rec,, 2011. © 2011 Wiley‐Liss, Inc.     

Cholecystokinin receptor antagonists increase the rat pup's preference toward maternal-odor and rug texture

The role of the cholecystokinin (CCK) system in mediating the infant's natural preferences toward maternal-related stimuli was examined by peripheral administration of selective CCK(A) and CCK(B) receptor antagonists (Devazepide and L-365,260, respectively) to 11-12-day-old rats and presenting them with a 3-minute preference test. In Experiment 1, the choice was between two floor textures, rug and plywood; the time spent on the relatively preferred side (rug) was measured. In Experiment 2, the odor of maternal faces emanated from one end of the test arena; time spent near that end was measured. These sensory stimuli were chosen as they represent olfactory and tactile aspects of the dam and nest. Compared to controls, both CCK receptor antagonists selectively increased the time spent on the preferred side, in both experiments, without affecting axillary temperature or locomotor activity. The results suggest that CCK may mediate and attenuate the infant's attraction toward naturally preferred stimuli.     

Differential novelty detection in rats selectively bred for novelty-seeking behavior

“Novelty-seeking” behavior describes the variability of rats’ locomotor response, namely high and low responders (HR and LR respectively), when exposed to a novel environment. Novelty-seeking in the rat is considered to model “sensation-seeking” in humans, a personality trait related to substance abuse. It is assumed that HR rats and LR rats differ in their emotional reactivity because of the disparate incentive value of contextual stimulus, thus differentially interacting with their environment. However, little is known about how HR and LR rats recognize novelty arising from the environment. The present study evaluates whether phenotype may affect spontaneous, non-spatial novelty discrimination. Selectively bred HR and LR rats were submitted to the novel-object recognition test. The task involved a delay of 3 h after a first encounter with an object (“old”), which had to be discriminated from a second object (“new”). Object discrimination was assessed minute-by-minute during a 3-min choice session. Amnesic effects of scopolamine (0.5 mg/kg, intraperitoneal) were also analyzed. HR-bred rats showed sustained novel-object recognition throughout the 3-min choice session, whereas LR-bred rats began to discriminate between objects only in the last minute. Surprisingly, level of discrimination in scopolamine-treated HR-bred rats was significant during the first minute of the choice test and diminished thereafter, presumably because both objects became equally familiar as they were explored. Additionally, scopolamine induced changes in muscarine M₂ receptor gene expression in a phenotype-dependent manner. Because consistent object discrimination mainly arises during the first minute, these findings may reflect differential novelty detection in HR-bred respect to LR-bred rats.