Spontaneous Object Recognition Test Research Articles

Votucalis, a Novel Centrally Sparing Histamine-Binding Protein, Attenuates Histaminergic Itch and Neuropathic Pain in Mice.

Votucalis is a biologically active protein in tick (R. appendiculatus) saliva, which specifically binds histamine with high affinity and, therefore, has the potential to inhibit the host’s immunological responses at the feeding site. We hypothesized that scavenging of peripherally released endogenous histamine by Votucalis results in both anti-itch and anti-nociceptive effects. To test this hypothesis, adult male mice were subjected to histaminergic itch, as well as peripheral nerve injury that resulted in neuropathic pain. Thus, we selected models where peripherally released histamine was shown to be a key regulator. In these models, the animals received systemic (intraperitoneal, i.p.) or peripheral transdermal (subcutaneous, s.c. or intraplantar, i.pl.) administrations of Votucalis and itch behavior, as well as mechanical and thermal hypersensitivity, were evaluated. Selective histamine receptor antagonists were used to determine the involvement of histamine receptors in the effects produced by Votucalis. We also used the spontaneous object recognition test to confirm the centrally sparing properties of Votucalis. Our main finding shows that in histamine-dependent itch and neuropathic pain models peripheral (s.c. or i.pl.) administration of Votucalis displayed a longer duration of action for a lower dose range, when compared with Votucalis systemic (i.p.) effects. Stronger anti-itch effect was observed after co-administration of Votucalis (s.c.) and antagonists that inhibited peripheral histamine H1 and H2 receptors as well as central histamine H4 receptors indicating the importance of these histamine receptors in itch. In neuropathic mice, Votucalis produced a potent and complete anti-nociceptive effect on mechanical hypersensitivity, while thermal (heat) hypersensitivity was largely unaffected. Overall, our findings further emphasize the key role for histamine in the regulation of histaminergic itch and chronic neuropathic pain. Given the effectiveness of Votucalis after peripheral transdermal administration, with a lack of central effects, we provide here the first evidence that scavenging of peripherally released histamine by Votucalis may represent a novel therapeutically effective and safe long-term strategy for the management of these refractory health conditions.

Oral treatment of 4-methylumbelliferone reduced perineuronal nets and improved recognition memory in mice

Hyaluronan (HA) is a core constituent of perineuronal nets (PNNs) that surround subpopulations of neurones. The PNNs control synaptic stabilization in both the developing and adult central nervous system, and disruption of PNNs has shown to reactivate neuroplasticity. We investigated the possibility of memory prolongation by attenuating PNN formation using 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis. Adult C57BL/6 mice were fed with chow containing 5% (w/w) 4-MU for 6 months, at a dose ~6.7 mg/g/day. The oral administration of 4-MU reduced the glycosaminoglycan level in the brain to 72% and the spinal cord to 50% when compared to the controls. Spontaneous object recognition test (SOR) performed at 2, 3, 6 and 7 months showed a significant increase in SOR score in the 6-months treatment group 24 h after object presentation. The effect however did not persist in the washout group (1-month post treatment). Immunohistochemistry confirmed a reduction of PNNs, with shorter and less arborization of aggrecan staining around dendrites in hippocampus after 6 months of 4-MU treatment. Histopathological examination revealed mild atrophy in articular cartilage but it did not affect the motor performance as demonstrated in rotarod test. In conclusion, systemic oral administration of 4-MU for 6 months reduced PNN formation around neurons and enhanced memory retention in mice. However, the memory enhancement was not sustained despite the reduction of PNNs, possibly due to the lack of memory enhancement training during the washout period. Our results suggest that 4-MU treatment might offer a strategy for PNN modulation in memory enhancement.

Retrieval-Induced Forgetting in a Pentylenetetrazole-Induced Epilepsy Model in the Rat.

The selective retrieval of some information may lead to the forgetting of related, but non-retrieved information. This memory phenomenon is termed retrieval-induced forgetting (RIF). Active inhibition is thought to function to resolve interference from competing information during retrieval, which results in forgetting. Epilepsy is associated with impaired inhibitory control that contributes to executive dysfunction. The purpose of this study is to investigate whether rats in a kindling model of epilepsy demonstrate normal levels of RIF. Rats were divided into two groups: saline and kindling. Pentylenetetrazole was injected intraperitoneally until the rats kindled. RIF was tested using a modified version of the spontaneous object recognition test, consisting of a sample phase, retrieval or interference phase, and a test phase. Exploration time for each object was analyzed. RIF was demonstrated in the saline group when rats subjected to the retrieval phase failed to discriminate between the familiar object and the novel object later in the test phase. Kindled rats, on the other hand, did not suffer forgetting even when they were subjected to the retrieval phase, as they spent significantly longer times exploring the novel rather than the familiar object in the test phase. Therefore, RIF was not observed in the kindling group. These findings indicate impaired retrieval-induced forgetting in kindled rats, which may be suggestive of a deficit in the inhibitory control of memory.

The effect of Wi-Fi electromagnetic waves in unimodal and multimodal object recognition tasks in male rats.

Wireless internet (Wi-Fi) electromagnetic waves (2.45GHz) have widespread usage almost everywhere, especially in our homes. Considering the recent reports about some hazardous effects of Wi-Fi signals on the nervous system, this study aimed to investigate the effect of 2.4GHz Wi-Fi radiation on multisensory integration in rats. This experimental study was done on 80 male Wistar rats that were allocated into exposure and sham groups. Wi-Fi exposure to 2.4GHz microwaves [in Service Set Identifier mode (23.6dBm and 3% for power and duty cycle, respectively)] was done for 30days (12h/day). Cross-modal visual-tactile object recognition (CMOR) task was performed by four variations of spontaneous object recognition (SOR) test including standard SOR, tactile SOR, visual SOR, and CMOR tests. A discrimination ratio was calculated to assess the preference of animal to the novel object. The expression levels of M1 and GAT1 mRNA in the hippocampus were assessed by quantitative real-time RT-PCR. Results demonstrated that rats in Wi-Fi exposure groups could not discriminate significantly between the novel and familiar objects in any of the standard SOR, tactile SOR, visual SOR, and CMOR tests. The expression of M1 receptors increased following Wi-Fi exposure. In conclusion, results of this study showed that chronic exposure to Wi-Fi electromagnetic waves might impair both unimodal and cross-modal encoding of information.

The role of transient receptor potential vanilloid type 1 in unimodal and multimodal object recognition task in rats.

The role of transient receptor potential vanilloid type 1 (TRPV1) channels in learning and memory processes has recently been recognized. In the present study, the role of this receptor in the multisensory integration process was investigated. This study was done using 96 male Wistar rats, which were kept in a reverse 12-12h dark/light cycle. Unimodal and multimodal object recognition task was performed by four variations of the spontaneous object recognition (SOR) test including standard SOR, tactile SOR, visual SOR, and cross-modal visual-tactile SOR (CMOR). AMG9810 (selective TRPV1 antagonist) was injected into the right lateral cerebral ventricle prior to sample and choice phases of SOR. A discrimination ratio was calculated to assess the preference of the animal for the novel object. Results demonstrated that administration of AMG9810 prior to the sample phase, as encoding phase, and prior to the choice phase, as retrieval phase, impaired discrimination between the novel and the familiar objects in all standard SOR, tactile SOR, visual SOR, and CMOR tasks (all p<0.05). The results of this study showed that TRPV1 receptors might be implicated in both unimodal and cross-modal encoding of information in rats.

Viral-mediated Zif268 expression in the prefrontal cortex protects against gonadectomy-induced working memory, long-term memory, and social interaction deficits in male rats

In humans, some males experience reductions in testosterone levels, as a natural consequence of aging or in the clinical condition termed hypogonadism, which are associated with impaired cognitive performance and mood disorder(s). Some of these behavioral deficits can be reversed by testosterone treatment. Our previous work in rats reported that sex differences in the expression of the transcription factor Zif268, a downstream target of testosterone, within the medial prefrontal cortex (mPFC) mediates sex differences in social interaction. In the present study, we aimed to examine the effects of gonadectomy (GNX) in male rats on mPFC Zif268 expression, mood and cognitive behaviors. We also examined whether reinstitution of Zif268 in GNX rats will correct some of the behavioral deficits observed following GNX. Our results show that GNX induced a downregulation of Zif268 protein in the mPFC, which was concomitant with impaired memory in the y-maze and spontaneous object recognition test, reduced social interaction time, and depression-like behaviors in the forced swim test. Reinstitution of mPFC Zif268, using a novel adeno-associated-viral (AAV) construct, abrogated GNX-induced working memory and long-term memory impairments, and reductions in social interaction time, but not GNX-induced depression-like behaviors. These findings suggest that mPFC Zif268 exerts beneficial effects on memory and social interaction, and could be a potential target for novel treatments for behavioral impairments observed in hypogonadal and aged men with declining levels of gonadal hormones.

Finding and Not Finding Rat Perirhinal Neuronal Responses to Novelty.

ABSTRACTThere is much evidence that the perirhinal cortex of both rats and monkeys is important for judging the relative familiarity of visual stimuli. In monkeys many studies have found that a proportion of perirhinal neurons respond more to novel than familiar stimuli. There are fewer studies of perirhinal neuronal responses in rats, and those studies based on exploration of objects, have raised into question the encoding of stimulus familiarity by rat perirhinal neurons. For this reason, recordings of single neuronal activity were made from the perirhinal cortex of rats so as to compare responsiveness to novel and familiar stimuli in two different behavioral situations. The first situation was based upon that used in “paired viewing” experiments that have established rat perirhinal differences in immediate early gene expression for novel and familiar visual stimuli displayed on computer monitors. The second situation was similar to that used in the spontaneous object recognition test that has been widely used to establish the involvement of rat perirhinal cortex in familiarity discrimination. In the first condition 30 (25%) of 120 perirhinal neurons were visually responsive; of these responsive neurons 19 (63%) responded significantly differently to novel and familiar stimuli. In the second condition eight (53%) of 15 perirhinal neurons changed activity significantly in the vicinity of objects (had “object fields”); however, for none (0%) of these was there a significant activity change related to the familiarity of an object, an incidence significantly lower than for the first condition. Possible reasons for the difference are discussed. It is argued that the failure to find recognition‐related neuronal responses while exploring objects is related to its detectability by the measures used, rather than the absence of all such signals in perirhinal cortex. Indeed, as shown by the results, such signals are found when a different methodology is used. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

Involvement of hippocampal NMDA receptors in retrieval of spontaneous object recognition memory in rats

The involvement of hippocampal N-methyl-d-aspartate (NMDA) receptors in the retrieval process of spontaneous object recognition memory was investigated. The spontaneous object recognition test consisted of three phases. In the sample phase, rats were exposed to two identical objects several (2–5) times in the arena. After the sample phase, various lengths of delay intervals (24h-6 weeks) were inserted (delay phase). In the test phase in which both the familiar and the novel objects were placed in the arena, rats’ novel object exploration behavior under the hippocampal treatment of NMDA receptor antagonist, AP5, or vehicle was observed. With 5 exposure sessions in the sample phase (experiment 1), AP5 treatment in the test phase significantly decreased discrimination ratio when the delay was 3 weeks but not when it was one week. On the other hand, with 2 exposure sessions in the sample phase (experiment 2) in which even vehicle-injected control animals could not discriminate the novel object from the familiar one with a 3 week delay, AP5 treatment significantly decreased discrimination ratio when the delay was one week, but not when it was 24h. Additional experiment (experiment 3) showed that the hippocampal treatment of an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, NBQX, decreased discrimination ratio with all delay intervals tested (24h-3 weeks). Results suggest that hippocampal NMDA receptors play an important role in the retrieval of spontaneous object recognition memory especially when the memory trace weakens.

Spontaneous object recognition: a promising approach to the comparative study of memory.

Spontaneous recognition of a novel object is a popular measure of exploratory behavior, perception and recognition memory in rodent models. Because of its relative simplicity and speed of testing, the variety of stimuli that can be used, and its ecological validity across species, it is also an attractive task for comparative research. To date, variants of this test have been used with vertebrate and invertebrate species, but the methods have seldom been sufficiently standardized to allow cross-species comparison. Here, we review the methods necessary for the study of novel object recognition in mammalian and non-mammalian models, as well as the results of these experiments. Critical to the use of this test is an understanding of the organism’s initial response to a novel object, the modulation of exploration by context, and species differences in object perception and exploratory behaviors. We argue that with appropriate consideration of species differences in perception, object affordances, and natural exploratory behaviors, the spontaneous object recognition test can be a valid and versatile tool for translational research with non-mammalian models.

Chronic transcranial focal stimulation from tripolar concentric ring electrodes does not disrupt memory formation in rats.

Non-invasive electrical brain stimulation has shown potential utility as a treatment for seizures in epilepsy patients. Transcranial focal stimulation (TFS) via tripolar concentric ring electrodes (TCREs) has been effective in reducing seizure severity in acute rodent models, but it has yet to be determined whether or not it will serve as a viable long-term treatment strategy. Prior experiments indicate that a single dose of TFS via TCRE does not impact short- or long-term memory formation. The present study investigated if five daily doses of TFS via a TCRE on the scalp affected the memory. The spontaneous object recognition (SOR) test was used to evaluate the memory. Sham and TFS-treated groups were evaluated and both showed comparable levels of preference for novel objects, indicating successful memory formation. More work on repeated dosage strategies is important for establishing the safety and efficacy of TFS as a putative treatment.

Retrieval-induced forgetting in rats.

"Retrieval-induced forgetting" in rats was evaluated using a modified spontaneous object recognition test. The test consisted of a sample phase, retrieval or interference phase, and a test phase with 60-min delay period inserted between the phases. Rats were randomly assigned to one of three groups (control, retrieval and interference) and allowed to explore the field in which two different objects (A, B) were placed in the sample phase. In the retrieval phase, two identical objects (B, B), which were the same as one of the objects presented in the sample phase, were placed again. In the interference phase, two identical objects (C, C), which were novel for animals, were placed. In the test phase, two different objects (A, D), one of which was identical to that presented in sample phase (familiar object) and the other was novel, were placed and the time spent exploring each object was analyzed. While the exploration of the novel object was significantly longer than that of the familiar object in rats subjected to the interference phase, rats subjected to the retrieval phase could not discriminate between the familiar and the novel objects at the test phase. These results demonstrate the "retrieval-induced forgetting" phenomenon in a spontaneous object recognition test in rats.

NCS-1 deficiency causes anxiety and depressive-like behavior with impaired non-aversive memory in mice

Sensing and regulating intracellular levels of calcium are essential for proper cellular function. In neurons, calcium sensing plays important roles in neuronal plasticity, neurotransmitter release, long-term synapse modification and ion channel activity. Neuronal calcium sensor-1 (NCS-1) is a member of the highly conserved neuronal calcium sensor family. Although NCS-1 has been associated with psychiatric conditions including autism, bipolar disorder and schizophrenia, it is unclear which role NCS-1 plays in behavior. To understand the involvement of NCS-1 in psychiatric conditions, we provided a comprehensive behavioral characterization of NCS-1 knockout (KO) mice. These mice grow and develop normally without apparent abnormalities in comparison to wild type littermates. However, open field showed that NCS-1 deficiency impairs novelty-induced exploratory activity in both KO and heterozygote (HT) mice. Moreover, NCS-1-deficiency also resulted in anxiety- and depressive-like behaviors as demonstrated by elevated plus maze, large open field, forced swim and tail suspension tasks. Furthermore, based on spontaneous object recognition test, non-aversive long-term memory was impaired in NCS-1 KO mice. In contrast, neither social behavior nor a kind of aversive memory was affected under NCS-1 deficiency. These data implicate NCS-1 in exploratory activity, memory and mood-related behaviors, suggesting that NCS-1 gene ablation may result in phenotypic abnormalities associated with neuropsychiatric disorders.

Effect of genetic homogeneity on behavioural variability in an object recognition test in cloned Göttingen minipigs

The number of animals used in research should be limited as much as possible. Among cloned animals, genetic variation is minimal and to the extent that behaviour is genetically determined inter-individual variability is expected to be higher among naturally bred animals. However, the cloning procedure per se might affect the resultant phenotype leading to phenotypic variations independent of the genetic background. Recently, cloned Göttingen minipigs carrying a mutation for Alzheimer's disease have been produced. In order to document the development of Alzheimer's disease symptoms, these pigs were subjected to a behavioural test of memory, the spontaneous object recognition test, from an early age. At ages 1 and 2 years no evidence of memory decline was found, yet the data showed striking behavioural variability among the cloned groups. The aim of the present study was to investigate effects of genetic homogeneity on variability of cloned minipigs compared with non-cloned controls regarding behavioural variables in a cognitive test, namely the spontaneous object recognition test.Significant differences in the variability between the cloned and control pigs were found in five out of 24 behavioural variables. The clones showed lower variability for four of the measures, whereas the variability was increased for one variable. No significant difference between the cloned and the control group was found for the remaining 19 variables (79%). In 14 of these, the standard deviation was numerically greater for the control group compared to the cloned group, indicating that variation may be less in cloned animals, but not demonstrable with the small group size of the present study (n=6 for each of the two groups tested).Overall, this study failed to show unambiguously that variability in these behavioural variables in cloned minipigs is less than in naturally bred control subjects and therefore does not directly support the hypothesis that cloning may be used to replicate animals in order to reduce group size in experimentation animals.

Object recognition as a measure of memory in 1–2 years old transgenic minipigs carrying the APPsw mutation for Alzheimer’s disease

Alzheimer's disease (AD) is a disabling, fatal disease, where animal models potentially can enable investigation of aetiology and treatment. The first litter of Göttingen minipigs carrying a mutation for human AD was born in 2007, showing transgene expression. In human AD patients, memory impairment is the most striking and consistent feature. The aim of the present study was to examine effects of the APPsw transgene on memory of AD minipigs compared with non-transgenic controls at two ages (1-2 years) using the spontaneous object recognition test (SORT), which is based on behavioural discrimination of familiar and novel objects. No significant difference between AD minipigs and controls was found when comparing object recognition as a measure of memory. The minipigs did explore the novel object significantly more than the familiar, indicating the expected recognition of the familiar object. Two different inter-phase intervals were used (IPI: 10-40 min). For both ages, object recognition was evident using 10 min IPI. When using 40 min IPI, object recognition was evident only at age 1 year. Comparing memory of a relatively small group of AD minipigs and controls at two rather young ages using the SORT, we were not able to show memory impairment in APPsw carrying minipigs. Being an age-dependent disease, the transgene is expected to cause AD-like symptoms in this porcine model, and the SORT should be repeated at older ages.

Dissociable anterograde amnesic effects of retrosplenial cortex and hippocampal lesions on spontaneous object recognition memory in rats

The amnesic effects of excitotoxic lesions of the rat retrosplenial cortex (RS) and hippocampus (HPC) in the spontaneous object recognition (SOR) performance were investigated. The SOR test consisted of the sample-exposure session(s) and a test session. First, to test retrograde amnesia, rats received four sample-exposure sessions within a day at 4 weeks and 1 day before the surgery, respectively. In the test sessions conducted 1 week after the surgery, both lesion groups showed a temporally ungraded retrograde amnesia. Second, to test anterograde amnesia, 1- and 4-week retention intervals were inserted between the four sample-exposure sessions and the test session. The RS-lesioned rats showed a retention interval-dependent impairment in the test sessions, while the HPC-lesioned rats showed an impairment regardless of the retention interval. Finally, to test short-term recognition memory, 5- or 30-min delay was interposed between the single sample-exposure session and the test session. Both lesion groups performed normally irrespective of the delay length. These results suggest that both the RS and HPC are important for long-term object recognition memory, but these areas have different roles in it.

Pre and post-natal exposure to ambient level of air pollution impairs memory of rats: the role of oxidative stress

The aims of this study were to evaluate whether air pollution during pre-natal and post-natal phases change habituation and short-term discriminative memories and if oxidants are involved in this process. As secondary objectives, it was to evaluate if the change of filtered to nonfiltered environment could protect the cortex of rats against oxidative stress as well as to modify the behavior of these animals. Wistar, male rats were divided into four groups (n = 12/group): pre and post-natal exposure until adulthood to filtered air (FA); pre-natal period to nonfiltered air (NFA-FA); until (21st post-natal day) and post-natal to filtered air until adulthood (PND21); pre-natal to filtered air until PND21 and post-natal to nonfiltered air until adulthood (FA-NFA); pre and post-natal to nonfiltered air (NFA). After 150 days of air pollution exposure, animals were tested in the spontaneous object recognition test to evaluate short-term discriminative and habituation memories. Rats were euthanized; blood was collected for metal determination; cortex dissected for oxidative stress evaluation. There was a significant increase in malondialdehyde (MDA) levels in the NFA group when compared to other groups (FA: 1.730 ± 0.217; NFA-FA: 1.101 ± 0.217; FA-NFA: 1.014 ± 0.300; NFA: 5.978 ± 1.920 nmol MDA/mg total proteins; p = 0.007). NFA group presented a significant decrease in short-term discriminative (FA: 0.603 ± 0.106; NFA-FA: 0.669 ± 0.0666; FA-NFA: 0.374 ± 0.178; NFA: −0.00631 ± 0.106 sec; p = 0.006) and an improvement in habituation memories when compared to other groups. Therefore, exposure to air pollution during both those periods impairs short-term discriminative memory and cortical oxidative stress may mediate this process.

The effect of the inter-phase delay interval in the spontaneous object recognition test for pigs

In the neuroscience community interest for using the pig is growing. Several disease models have been developed creating a need for validation of behavioural paradigms in these animals. Here, we report the effect of different inter-phase delay intervals on the performance of Göttingen minipigs in the spontaneous object recognition test. The test consisted of a sample and a test phase. First, the pigs explored two similar objects. After a 10-min, 1-h, or 24-h delay two different objects were presented; one familiar from the sample phase and one novel. An exploration-time difference between the novel and the familiar object was interpreted as recognition of the familiar object. We scored the exploration times both manually and automatically, and compared the methods. A strong discrimination between novel and familiar objects after a 10-min inter-phase delay interval and no discrimination after 24 h were found in our set-up of the spontaneous object recognition test. After a 1-h delay, the pigs still showed a significant habituation to the familiar object, but no discrimination was observed. Discrimination between the two objects was mainly confined to the first half of the test phase, and we observed a high between-subject variation. Furthermore, automatic tracking was valid for determination of habituation and discrimination parameters but lead to an overestimation of individual measurements. We conclude that the spontaneous object recognition test for pigs is sensitive to increasing inter-phase delay intervals, and that automatic data acquisition can be applied.

Objects as enrichment: Effects of object exposure time and delay interval on object recognition memory of the domestic pig

A modified spontaneous object recognition test was used to examine object recognition memory in the domestic pig. This test uses preference for a novel object over a previously encountered sample object as indicating recognition of the sample object, and no preference as indicating no recognition. Two factors hypothesized to affect object recognition are duration of exposure to the sample stimulus and delay interval before re-exposure. Both of these factors could be manipulated in a rotational object enrichment program for pigs. Reducing exposure time and increasing the delay interval before re-exposure should decrease object recognition and prolong novelty-induced object exploration. We exposed 5-week-old pigs to different sample objects in their home pens for 10 min and 2 days, respectively. We tested for object recognition memory at various delay intervals after initial exposure by placing littermate pairs in a test pen for 10 min and recording snout contact with a sample object and a completely novel object. At a 1-h delay, half the pairs were tested with the 2-day sample object; the other half received the 10-min sample object. At a 3-h delay, pairs were tested with the opposite sample object. Pairs were also tested with the 2-day sample at a 5-day delay and the 10-min sample at a 6-day delay. We predicted that pigs would show a preference for the novel versus the 2-day sample object at all three delays, but would only prefer the novel object over the 10-min sample object at the 1-h and 3-h delays. Pigs did not show novelty preference in the presence of the 10-min sample object at any delay. Novelty preference in the presence of the 2-day sample object occurred at the 3-h ( P < 0.05) and 5-day delays ( P < 0.001), but not the 1-h delay. The lack of novelty preference when pigs were tested with the 10-min sample object may have been due to failure to habituate to the sample object. Testing in a different location from the initial sample object exposure and retroactive interference from exposure to the 10-min sample object may have contributed to a temporary lack of novelty preference when pigs were tested with the 2-day sample object at the 1-h delay. The finding that pigs retained a memory for the 2-day sample object for at least 5 days suggests that restricting object exposure to less than 2 days may help to preserve the exploratory value of objects rotated among pens.

The effect of chronic peripubertal cannabinoid treatment on deficient object recognition memory in rats after neonatal mPFC lesion

We here report on behavioral effects of neonatal medial prefrontal cortex (mpfc) lesions in rats, followed by chronic peripubertal treatment with the cannabinoid full agonist WIN 55,212-2 (WIN). Rat pups received excitotoxic lesions of the mpfc on postnatal day (pd) 7. Chronic WIN (1.2 mg/kg) treatment was extended throughout the rats' puberty (pd 40–65). All animals were tested as juveniles and adults for short-term memory functioning using the spontaneous object recognition test, and for locomotor activity in an open field. Lesioned rats showed impairments in recognition memory when tested prepubertally. Postpubertal testing of lesioned animals revealed a persisting recognition memory impairment that was intensified by pubertal WIN treatment. Chronic WIN treatment during puberty also affected recognition memory in sham-lesioned rats and controls. No effects on locomotor activity of either neonatal lesion or pubertal cannabinoid treatment were found. This study shows that behavioral deviations induced by neonatal mPFC lesions can be exacerbated by pubertal chronic cannabinoid treatment, leading to long-lasting impairments of mnemonic short-term information processing.

Hippocampal lesions that abolish spatial maze performance spare object recognition memory at delays of up to 48 hours

The hippocampus is widely considered to be a critical component of a medial temporal lobe memory system, necessary for normal performance on tests of declarative memory. Object recognition memory is thought to be a classic test of declarative memory function. However, previous tests of the effects of hippocampal lesions on object recognition memory have not always supported this view. One possible reason for this inconsistency is that previously reported effects of hippocampal lesions on object recognition memory tasks may have stemmed not from a deficit in object recognition memory per se, but as a result of spatial and contextual confounds in the task. Thus, in the present study, we used a spontaneous object recognition test in a modified apparatus designed to minimize spatial and contextual factors. A group of rats with complete excitotoxic lesions of the hippocampus and a group of control rats were tested on this modified spontaneous object recognition task with retention delays of up to 48 h. These rats were also tested on a spatial nonmatching-to-place task. Spatial memory performance was abolished following hippocampal lesions, whereas performance on the recognition memory task was intact at all delays tested.