Non-spatial Novelty Research Articles

Impaired response to novelty and motor behaviour in the D-Gal rat model of accelerated aging.

Event Abstract Back to Event Impaired response to novelty and motor behaviour in the D-Gal rat model of accelerated aging. Beatriz Vila-Verde1*, Diana Reis-Borges1, Carlos Nascimento2 and Diana Cunha-Reis1, 2* 1 Institute of Biosystems and Integrative Sciences (BioISI), Portugal 2 Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Portugal Aging causes multiple physiological changes like cognitive decline, sympathoexcitation, impaired motor function and enhanced susceptibility to oxidative damage. We evaluated the relation between motor function, cognitive performance and selective synaptic markers in a rat model of accelerated aging (AA). AA was induced in 12-week-old male Wistar rats by D-galactose (250 mg/Kg) administration for 40 days and compared to Sham (saline injections) and 12-month old (natural aging) rats. The behavioural evaluation was performed with the open-field test1 for locomotion and exploratory traits, with the rotarod for motor performance, with elevated plus maze test for anxiety, and with the water maze for spatial memory acquisition. Novelty response was evaluated in the holeboard with objects for responses to spatial mismatch novelty2 and by the novel object recognition test3 for non-spatial novelty. Hippocampal expression of tyrosine hydroxilase (TH), flotilin and caveolin in hippocampal membranes was evaluated by western blot. AA rats showed decreased body weight, impaired exploration and motor performance, and mild cognitive impairment compared to sham controls but not so pronounced as naturally aged rats. Responses to spatial novelty were also impaired in AA rats but not responses to presentation of novel objects. AA rats did not show anxious behaviour when compared to Sham controls. Altogether this suggests that the changes observed in this model are not irreversible and do not fully reproduce the physiological responses to aging. Acknowledgements Supported by FCT (SFRH/ BPD/81358/2011; PTDC/SAU-PUB/28311/2017). References 1- Crusio et al. Behav Brain Res, 1989, 32:75; 2-Goh et al., Cereb Cortex, 2013, 23:129; 3-Goh et al., Cereb Cortex 2013 23:1118. Keywords: Aging, Hippocampus, novelty, Learning, Dopamine Conference: XVI Meeting of the Portuguese Society for Neuroscience (SPN2019), Lisboa, Portugal, 30 May - 1 Jun, 2019. Presentation Type: Poster presentation Topic: Neurodegeneration / Physiological Aging Brain Citation: Vila-Verde B, Reis-Borges D, Nascimento C and Cunha-Reis D (2019). Impaired response to novelty and motor behaviour in the D-Gal rat model of accelerated aging.. Front. Cell. Neurosci. Conference Abstract: XVI Meeting of the Portuguese Society for Neuroscience (SPN2019). doi: 10.3389/conf.fncel.2019.01.00002 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Feb 2019; Published Online: 27 Sep 2019. * Correspondence: Ms. Beatriz Vila-Verde, Institute of Biosystems and Integrative Sciences (BioISI), Lisbon, 1749-016, Portugal, beatriz.vilaverdes@gmail.com Dr. Diana Cunha-Reis, Institute of Biosystems and Integrative Sciences (BioISI), Lisbon, 1749-016, Portugal, dcreis@fc.ul.pt Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Beatriz Vila-Verde Diana Reis-Borges Carlos Nascimento Diana Cunha-Reis Google Beatriz Vila-Verde Diana Reis-Borges Carlos Nascimento Diana Cunha-Reis Google Scholar Beatriz Vila-Verde Diana Reis-Borges Carlos Nascimento Diana Cunha-Reis PubMed Beatriz Vila-Verde Diana Reis-Borges Carlos Nascimento Diana Cunha-Reis Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Involvement of CA1 GABAA Receptors in Ketamine-Induced Impairment of Spatial and Non-Spatial Novelty Detection in Mice

Inhibitory GABAergic and excitatory glutamatergic neurons from multiple brain areas, send fibers to the hippocampal CA1 region. NMDA receptors have been identified as important compoents of the brain system underlying memory formation, which that through an increase in glutamate-mediated neurotransmission. Ketamine and other NMDA receptor antagonists produce deficits in cognitive tasks, including both spatial and non-spatial memory. In the current study, we tested whether the activation or inhibition of GABAA receptors in CA1 hippocampal of mice has an impact on ketamine (NMDA antagonist) induced spatial and non-spatial novelty detection deficits. Adult male mice weighing between 25–30 g were used. The open-field method was used to evaluate spatial and non-spatial memory information. Data obtained from the present study revealed that an intra-CA1 injection with a sub-threshold dose the GABAA receptor antagonist bicuculline (0.0625 µg mouse) disrupted spatial memory but restored non-spatial memory induced by lower and higher doses of ketamine (0.05 and 0.01 mg/kg) respectively. Meanwhile, the co-administration of the intra-CA1 injection with a sub-threshold dose of muscimol (GABAA receptor agonist at 0.25 µg/mouse) and a lower dose of ketamine could only impair the ability of non-spatial change detection but could not alter spatial novelty. In conclusion, ketamine (which contributes to the impairment of memory trace stored in the hippocampus) may be generated from GABAA receptors of CA1 neurons and their blockade could prevent these effects.

Processing of spatial and non-spatial information in rats with lesions of the medial and lateral entorhinal cortex: Environmental complexity matters

The entorhinal-hippocampal circuitry has been suggested to play an important role in episodic memory but the contribution of the entorhinal cortex remains elusive. Predominant theories propose that the medial entorhinal cortex (MEC) processes spatial information whereas the lateral entorhinal cortex (LEC) processes non spatial information. A recent study using an object exploration task has suggested that the involvement of the MEC and LEC spatial and non-spatial information processing could be modulated by the amount of information to be processed, i.e. environmental complexity. To address this hypothesis we used an object exploration task in which rats with excitotoxic lesions of the MEC and LEC had to detect spatial and non-spatial novelty among a set of objects and we varied environmental complexity by decreasing the number of objects or amount of object diversity. Reducing diversity resulted in restored ability to process spatial and non-spatial information in MEC and LEC groups, respectively. Reducing the number of objects yielded restored ability to process non-spatial information in the LEC group but not the ability to process spatial information in the MEC group. The findings indicate that the MEC and LEC are not strictly necessary for spatial and non-spatial processing but that their involvement depends on the complexity of the information to be processed.

Cellular activation of hypothalamic hypocretin/orexin neurons facilitates short-term spatial memory in mice

The hypothalamic hypocretin/orexin (HO) system holds a central role in the regulation of several physiological functions critical for food-seeking behavior including mnemonic processes for effective foraging behavior. It is unclear however whether physiological increases in HO neuronal activity can support such processes. Using a designer rM3Ds receptor activation approach increasing HO neuronal activity resulted in improved short-term memory for novel locations. When tested on a non-spatial novelty object recognition task no significant difference was detected between groups indicating that hypothalamic HO neuronal activation can selectively facilitate short-term spatial memory for potentially supporting memory for locations during active exploration.

The modulatory effect of CA1 GABAb receptors on ketamine-induced spatial and non-spatial novelty detection deficits with respect to Ca2+

Glutamate and γ-aminobutyric acid (GABA) are among the most abundant neurotransmitters in the central nervous system. Ketamine and other noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists are known to induce deficits in learning and the performance of cognitive tasks. The present study was designed to assess the effects of dorsal hippocampal (CA1) GABAb receptors on ketamine-induced spatial and non-spatial memory deficits with regard to the role of Ca2+ as a defining factor. Spatial and non-spatial novelty detection of male NMRI mice were investigated in a circular open-field apparatus. According to our results, the intraperitoneal injection of ketamine at its higher dose (0.1mg/kg) impaired both spatial and non-spatial novelty detection. Moreover, the intra-CA1 injection of baclofen (a GABAb receptor agonist) at higher doses (0.02 and 0.2μg/mouse) impaired the spatial but not non-spatial novelty detection. In addition, phaclofen (a GABAb receptor antagonist at 0.2μg/mouse) impaired both spatial and non-spatial novelty detection. Baclofen restored and induced a modulatory effect on ketamine-induced responses in the spatial and non-spatial novelty detection task, respectively. On the contrary, phaclofen restored and induced a modulatory effect on ketamine-induced responses in the non-spatial and spatial novelty detection task, respectively. Finally, the subthreshold dose of SKF96365 (a Ca2+ channel blocker) impaired only the spatial but not non-spatial restoration effects of baclofen or phaclofen following a higher dose of ketamine. Such findings suggest that the ketamine-induced impairment of memory consolidation may occur through GABAb receptors of the CA1 neurons. Moreover, baclofen and phaclofen were shown to possibly exert their effects on the ketamine-induced spatial novelty detection deficits through Ca2+ channels.

Modulation of the effects of the cannabinoid agonist, ACPA, on spatial and non-spatial novelty detection in mice by dopamine D1 receptor drugs infused into the basolateral amygdala

AimThe amygdala is a major target of midbrain dopaminergic neurons and is implicated in learning and memory processes. This study investigates the effect of basolateral amygdale (BLA) dopamine receptors on spatial and non-spatial novelty detection deficit, induced by a selective CB1 cannabinoid receptor agonist (Arachidonylcyclopropylamide; ACPA), during a non-associative task. MethodsMale mice weighing 30–35g were used. Open field procedure was employed to assess the spatial and non-spatial memory retention. ResultsOur data showed that post-training intraperitoneal injection of ACPA (0.02mg/kg), intra-BLA microinjection of SKF38393 (D1 dopamine receptor agonist; at higher dose, 0.1μg/mouse) and SCH23390 (D1 dopamine receptor antagonist; at lowest dose, 0.005μg/mouse) impaired both spatial and non-spatial novelty detection. Moreover, intra-BLA microinjection of subthreshold dose of SKF38393 or SCH23390 restored and potentiated the spatial and non-spatial novelty detection impairment caused by ACPA, respectively. ConclusionOur results suggested that the ACPA induced impairment of memory retention, may occur through BLA D1 dopamine receptors.

Impairing effect of amphetamine and concomitant ionotropic glutamate receptors blockade in the ventral striatum on spatial learning in mice

Accumulating evidence supports the involvement of the ventral striatum (VS) in spatial information processing. The multiple cortical glutamatergic and mesolimbic dopaminergic (DAergic) afferences on the same neurons in the ventral striatum provide the neuroanatomical substrate for glutamate and dopamine functional interaction. However, there is little evidence in the literature on how this interaction affects the ability to encode spatial information. First, we evaluated the effect of intra-VS bilateral infusion of different doses of amphetamine (0.3, 0.75, and 1.5 μg/side) on the ability to detect spatial novelty in mice. Next, we examined the impact produced on the same abilities by intra-VS infusion of ineffective doses of amphetamine (0.3 μg/side) in association with N-methyl-D-aspartate (NMDA) (3.125 ng/side) or α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) (0.25 ng/side) receptor antagonist. The results show that infusion of amphetamine impairs detection of spatial novelty, affecting also exploratory activity and marginally the detection of nonspatial novelty. In contrast, an association of subthreshold doses of amphetamine with NMDA or AMPA receptor antagonists exerted a selective effect on reactivity to a spatial change. These findings demonstrate that enhanced DAergic activity in the VS enhances glutamate receptor antagonist-induced impairment in learning and memory.

Involvement of the CA1 GABAA receptors in ACPA-induced impairment of spatial and non-spatial novelty detection in mice

RationaleCannabinoids are shown to modulate the hippocampal memory processing through different neuronal systems such as GABAergic and glutamatergic. This study investigates the effects of dorsal hippocampal (CA1) GABAA receptors on spatial and non-spatial novelty detection deficit, induced by a selective CB1 receptor agonist (ACPA), during a non-associative task. MethodsMale mice weighing 30–35g were used. Open field paradigm was employed to assess the spatial and non-spatial memory retention. ResultsOur data showed that intraperitoneal injection of the higher doses of ACPA (0.005, 0.01 and 0.02mg/kg) decreases spatial change detection as well as the reaction to non-spatial novelty. Moreover, isolated intra-CA1 injection of bicuculline (GABAA receptor antagonist) at 0.0625, 0.125 and 0.25μg/mouse did not alter the spatial change detection and non-spatial novelty in saline treated mice. On the other hand, intra-CA1 injection of the higher doses of muscimol (GABAA receptor agonist) at 0.25, 0.5 and 1μg/mouse, not only impaired the spatial change detection on its own, but also affected the reaction to non-spatial novelty. In addition, the subthreshold dose of bicuculline reversed the impaired spatial and non-spatial memory in mice which received post-training injection of ACPA effective dose (0.02mg/kg). Meanwhile, co-administration of the subthreshold and effective doses of muscimol and ACPA (0.005mg/kg) could only impair the spatial change detection ability but not the reaction to non-spatial novelty. ConclusionOur results suggested that the ACPA induced impairment of memory retention, may occur through dorsal hippocampal (CA1) GABAA receptors thus, blockade of these receptors can possibly reverse this phenomenon.

Dopamine–Glutamate Interplay in the Ventral Striatum Modulates Spatial Learning in a Receptor Subtype-Dependent Manner

The ventral striatum (VS) is characterized by a distinctive neural architecture in which multiple corticolimbic glutamatergic (GLUergic) and mesolimbic dopaminergic (DAergic) afferents converge on the same output cell type (the medium-sized spiny neuron, MSN). However, despite the gateway function attributed to VS and its involvement in action selection and spatial navigation, as well as the evidence of physical and functional receptor-receptor interaction between different members of ionotropic GLUergic and DAergic receptors, there is no available knowledge that such reciprocal interaction may be critical in shaping the ability to learn novel spatial and non-spatial arrangement of stimuli. In this study, it was evaluated whether intra-VS bilateral infusion of either N-methyl-D-aspartate (NMDA) or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-selective antagonists may suppress the ability to detect spatial or non-spatial novelty in a non-associative behavioral task. In a second set of experiments, we further examined the hypothesis that VS-mediated spatial information processing may be subserved by some preferential receptor-receptor interactions among specific GLUergic and DAergic receptor subtypes. This was assessed by concomitant intra-VS infusion of the combination between subthreshold doses of either NMDA or AMPA receptor antagonists with individual D1 or D2 receptor blockade. The results of this study highlighted the fact that NMDA or AMPA receptors are differentially involved in processing of spatial and non-spatial novelty, and showed for the first time that preferential NMDA/D1 and AMPA/D2 receptor-receptor functional communication, but not NMDA/D2 and AMPA/D1, is required for enabling learning of novel spatial information in the VS.

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 M 2 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.

Impairment of novelty detection in mice targeted for the Chl1 gene

A deficit in cell adhesion molecules including the human Chl1 (close homologue of the L1 cell adhesion molecule) gene may cause impairment of cognitive processes. Aberrant connectivity in the CA3 region of the hippocampus has been reported in mice lacking the CHL1 protein after Chl1 gene targeting. Previous studies have observed a deficit in the processing of novel information by CHL1-deficient mice. We investigated deficits in spatial discrimination and object discrimination in three groups of mice — Chl1 +/+, Chl1 +/− and Chl1 −/− — performing spatial and object novelty tasks. The results indicated that wild-type mice easily recognized objects that were either “displaced” or “substituted”. Chl1 −/− mice showed severe impairment of the capacity to react to both spatial and non-spatial novelty. Chl1 +/− mice were severely restricted in their ability to detect spatial changes, but succeeded in novel object discrimination. A dose-dependent sensitivity of the organization of the CA3 layer to the CHL1 protein may explain this result. However, the observations suggest that a dysfunction of parts of the brain other than the hippocampus may be involved in the impairment.

Disruption of the direct perforant path input to the CA1 subregion of the dorsal hippocampus interferes with spatial working memory and novelty detection

Subregional analyses of the hippocampus suggest CA1-dependent memory processes rely heavily upon interactions between the CA1 subregion and entorhinal cortex. There is evidence that the direct perforant path (pp) projection to CA1 is selectively modulated by dopamine while having little to no effect on the Schaffer collateral (SC) projection to CA1. The current study takes advantage of this pharmacological dissociation to demonstrate that local infusion of the non-selective dopamine agonist, apomorphine (10, 15μg), into the CA1 subregion of awake animals produces impairments in working memory at intermediate (5min), but not short-term (10s) delays within a delayed non-match-to-place task on a radial arm maze. Sustained impairments were also found in a novel context with similar object–space relationships. Infusion of apomorphine into CA1 is also shown here to produce deficits in spatial, but not non-spatial novelty detection within an object exploration paradigm. In contrast, apomorphine produces no behavioral deficits when infused into the CA3 subregion or overlying cortex. These behavioral studies are supported by previous electrophysiological data that demonstrate local infusion of the same doses of apomorphine significantly modifies evoked responses in the distal dendrites of CA1 following angular bundle stimulation, but produces no significant effects in the proximal dendritic layer following stimulation of the SC. These results support a modulatory role for dopamine in EC–CA1, but not CA3–CA1 circuitry, and suggest the possibility of a fundamental role for EC–CA1 synaptic transmission in terms of detection of spatial novelty, and intermediate-term, but not short-term spatial working memory or object-novelty detection.

Spatial deficits in a mouse model of Parkinson disease

Accumulating evidence in humans demonstrated that visuo-spatial deficits are the most consistently reported cognitive abnormalities in Parkinson disease (PD). These deficits have been generally attributed to cortical dopamine degeneration. However, more recent evidence suggests that dopamine loss in the striatum is responsible for the visuo-spatial abnormalities in PD. Studies based on animal models of PD did not specifically address this question. Thus, the first goal of this study was to analyze the role of dopamine within the dorsal striatum in spatial memory. We tested bilateral 6-OHDA striatal lesioned CD1 mice in an object-place association spatial task. Furthermore, to see whether the effects were selective for spatial information, we measured how the 6-OHDA-lesioned animals responded to a non-spatial change and learned in the one-trial inhibitory avoidance task. The results demonstrated that bilateral (approximately 75%) dopamine depletion of the striatum impaired spatial change discrimination. On the contrary, no effect of the lesion was observed on non-spatial novelty detection or on passive avoidance learning. These results confirm that dopamine depletion is accompanied by cognitive deficits and demonstrate that striatal dopamine dysfunction is sufficient to induce spatial information processing deficits.

Behavioral characterization of a transection of dorsal CA3 subcortical efferents: Comparison with scopolamine and physostigmine infusions into dorsal CA3

Cholinergic projections from the medial septum and diagonal band of Broca into the hippocampus have long been implicated in learning and memory. Projections from CA3 to neurons in the medial septum and the diagonal band of Broca have been anatomically characterized. The present experiments were designed to evaluate interactions between the dorsal CA3 subcortical efferents and the cholinergic efferents from the medial septum and diagonal band of Broca for spatial and nonspatial (visual object) novelty detection in the rat. In Experiment 1, physostigmine and scopolamine (both 0.4 μL at 30 μM) were infused into dorsal CA3 and animals were tested on a spatial and nonspatial (visual object) novelty detection paradigm. Scopolamine infusions into dorsal CA3 caused deficits for both spatial and nonspatial (visual object) novelty detection. Physostigmine infusions into dorsal CA3 enhanced both spatial and nonspatial (visual object) novelty detection. These data support models proposing that acetylcholine may control the dynamics for encoding, consolidation, and retrieval in the hippocampus. In Experiment 2, a selective transection of dorsal CA3 efferents in the fimbria resulted in deficits for spatial and nonspatial (visual object) novelty detection. These deficits were similar to the deficits caused by scopolamine infusions into dorsal CA3. These data demonstrate that dorsal CA3 and the medial septum/diagonal band of Broca interact, and that dorsal CA3 influences cholinergic inputs into the hippocampus to facilitate encoding.

NGF induces appearance of adult-like response to spatial novelty in 18-day male mice

We investigated the effects of Nerve Growth Factor (NGF) administration on the maturation of reactivity to spatial and non-spatial novelty in developing mice. CD-1 mice of both sexes received intracerebral administration of NGF on postnatal day (pnd) 15, and their response to object displacement (spatial novelty) and object substitution (object novelty) were assessed in a spatial open-field with four objects on pnd 18 or 28. On pnd 18, NGF induced only in males precocious appearance of spatial novelty discrimination, while increasing choline acetyltransferase activity in neocortex and hippocampus of both sexes. The behavioral and neurochemical effects disappeared by pnd 28. NGF triggers adult-like responding to spatial novelty in developing mice and such effect is gender-specific.

Long-term effects of developmental exposure to zidovudine on exploratory behavior and novelty discrimination in CD-1 mice

Long-term changes in exploratory, social and agonistic behavior have been reported in rodents following developmental exposure to zidovudine (AZT), an agent commonly administered to pregnant seropositive women and their neonates to prevent HIV-1 transmission. The present study evaluates the effects of either prenatal or prolonged AZT treatment on spatial and nonspatial novelty discrimination in mice, using an open-field test with four objects, in which responses to both spatial rearrangement of familiar objects and object novelty are assessed. AZT (160 mg/kg) or Saline was given orally twice daily to pregnant mice from gestational days (GD) 10 to 19 (Experiment 1) or from GD 10 to lactation day 10 (Experiment 2). Offspring of both sexes were tested on postnatal day (PND) 28, 45 or 70. Depending on treatment schedule, AZT altered different behavioral responses, males being more affected than females. The prenatal treatment (Experiment 1) reduced exploration of the objects at all ages considered and increased wall and top rearing at ages 45 and 70. Following prolonged treatment (Experiment 2), AZT offspring were markedly more active than controls and displayed more wall rearing at age 70 while showing lower grooming frequency at all ages. Both AZT and control mice failed to respond to object rearrangement at adulthood, a discrepancy from previous data, which is discussed in relation to perinatal stress effects.

Role of dopaminergic system in reactivity to spatial and non-spatial changes in mice.

While experimental evidence shows that dopamine (DA) systems have an important role in locomotor function and in motivation, their role in the reactivity to spatial and non-spatial novelty is less well established. In this study, we investigated the effects of dopaminergic pharmacological manipulation on the capability of CD1 mice to encode spatial and non-spatial information in an open field with objects. The effects of systemic administration of: (1) selective D1 and D2 antagonists (SCH23390, 0.015 mg/kg or 0.020 mg/kg; sulpiride, 10 mg/kg or 20 mg/kg); (2) direct and indirect DA agonists (apomorphine, 1 mg/kg or 2 mg/kg; amphetamine, 1 mg/kg or 2 mg/kg) were studied. On the one hand, systemic administration of either D1 or D2 antagonists induced a selective impairment in the detection of spatial change but did not affect reaction to non-spatial novelty. On the other hand, amphetamine induced a selective decrease in exploratory activity in the first three sessions. This decrease did not affect the ability of mice to react to spatial change, but a dose-dependent decrease was observed in reactivity to non-spatial novelty. Such an effect does not seem to be due to amphetamine-induced hyperactivity or to non-DA mechanisms, since apomorphine induced a similar neophobic profile, without affecting locomotion. Taken together, these results demonstrate that manipulations of DA transmission affect reactivity to spatial and non-spatial novelty. In particular, we suggest that these two behavioral responses are modulated in opposite ways by the DA system.

Effects of lesions to the glutamatergic afferents to the nucleus accumbens in the modulation of reactivity to spatial andnon-spatial novelty in mice

The purpose of this study was to compare the effects of selective lesions of the three main sources of limbic afferents to the nucleus accumbens—fornix, prelimbic cortex and amygdala—with those induced by N-methyl- d-aspartate receptor blockage in this structure, in a non-associative task designed to estimate the ability of rodents to encode spatial and non-spatial relationships between discrete stimuli. The task consists of placing mice in an open field containing five objects and, after three sessions of habituation, examining their reactivity to object displacement (spatial novelty) and object substitution (object novelty). Focal administrations of the competitive N-methyl- d-aspartate antagonist dl-2-amino-5-phosphonopentanoic acid (0.1 μg/side) induced a selective impairment in the ability of mice to react to the spatial change. Lesions to the different structures affect the response of mice to spatial and non-spatial novelty in different ways. In particular, while fornix lesions induced a decrease in re-exploration of the displaced objects, prelimbic cortex lesions enhanced the exploration of both displaced and non-displaced objects. Finally, the basolateral amygdala lesions did not induce any impairment in the detection of the displaced objects but decreased the latencies to approach novel objects. It is concluded that N-methyl- d-aspartate receptor blockage in the nucleus accumbens subsumes the effects of the three lesions. Some hypotheses on the role of glutamatergic transmission in the accumbens on information processing are briefly discussed.