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Biomedical subjects

Giovanni Laviola

Publications and source records attributed to Giovanni Laviola.

At least 19 recordsLinked to original sources
PubMed2006

Impulsivity-anxiety-related behavior and profiles of morphine-induced analgesia in heterozygous reeler mice.

Reelin is an extracellular matrix protein, secreted by GABAergic interneurons, that provides a signal for neural plasticity. A downregulation of reelin may be a factor to be considered in the study of major psychiatric disorders. The heterozygous reeler mouse model, thus, may be important to reveal those alterations in behavioral phenotype produced by reduced neural plasticity. Heterozygous (HZ) and wild-type (WT) mice were tested for anxiety-related behavior, motor impulsivity, and morphine-induced analgesia. Heterozygous mice showed significantly lower levels of anxiety- and risk-assessment-related behaviors in the elevated plus-maze during adolescence, in the absence of basal changes in general locomotion. Adult mice were assessed for profiles of impulsive behavior in operant chambers, and HZ mice exhibited elevated levels of motor impulsivity. When mice were assessed in nociception tests, a genotype difference in morphine-induced analgesia was found, and these results were confirmed by measurement of mu-receptors in the midbrain. The basal behavioral profile of the HZ genotype reveals important differences, consistent with decreased behavioral inhibition and emotionality, which can be revealed as early as in adolescence, together with slight increment of impulsive behavior and altered pain threshold and at the adult age. The HZ genotype can thus represent a useful animal model for the study of behavioral disorders consequent to reduced neural plasticity.

Analgesics, Opioid↗
PubMed2006

Neurobehavioural disorders in the infant reeler mouse model: interaction of genetic vulnerability and consequences of maternal separation.

Studies on heterozygous (HZ) reeler mice suggest a relationship between reelin (a protein of extra cellular matrix) haploinsufficiency and the presence of altered neural networks and behaviour. Neonatal adverse and/or stimulating experiences might interfere with the emergence of this genetic-dependent phenotype. Repeated episodes of maternal separation early in ontogeny result in enduring neuroendocrine, neurochemical and behavioural alterations in the offspring. Therefore, in order to investigate whether developmental indexes of neurobehavioural disorders can be studied in the infant reeler mouse model, and whether ontogenetic adverse experiences may question or improve its suitability, homozygous reeler (RL), heterozygous (HZ) and wild-type (WT) mouse pups underwent maternal separation (SEP, 5h/day) or handling (H, 3min/day) on PND 2-6. As expected, a sex difference appeared, for measure of emotional and communicative behaviour in infant mice. On PND 7, compared to other genotypes, RL mouse pups from the H control group, showed reduced levels of ultrasound (USV) production and of locomotion. Surprisingly, this deficit in RL mice was fully reverted by maternal separation. Maternal separation per se reduced social motivation in the homing test at PND 9 in WT mice, with no effects on HZ and RL ones. Additionally, female pups emitted much lower levels of ultrasound production than males within the H control group. Such a baseline sex difference, however, disappeared in the SEP group. The present results provide evidence that unusual stress and related hormonal stimulation early in development may (i) independently shape individual phenotype and (ii) interact with a genetic make-up to substantially modify its "natural" developmental trajectories.

Animals↗
PubMed2006

Subchronic nicotine exposure in adolescence induces long-term effects on hippocampal and striatal cannabinoid-CB1 and mu-opioid receptors in rats.

There is evidence for the existence of functional interactions between nicotine and cannabinoids and opioid compounds in adult experimental animals. However, there is scarce information about these relationships in young animals. In the present study we evaluated short and long-term effects of a subchronic nicotine treatment [0.4 mg/kg daily i.p. injections from postnatal day (PND) 34 to PND 43], upon hippocampal and striatal cannabinoid-CB(1) and mu-opioid receptors in Wistar rats of both genders. Rats were sacrificed 2 h after the last nicotine injection (short-term effects, PND 43) or one month later (long-term effects, PND 75). Hippocampal and striatal cannabinoid CB(1) and mu-opioid receptors were quantified by Western blotting. The subchronic nicotine treatment induced a region-dependent long-lasting effect in cannabinoid CB(1) receptor: a significant increase in hippocampal cannabinoid CB(1) receptors and a significant decrease in striatal cannabinoid CB(1) receptors, with these effects being similar in males and females. With respect to mu-opioid receptors, subchronic nicotine induced a significant down-regulation in hippocampal and striatal mu-opioid receptors in the long-term, and within the striatum the effects were more marked in adult males than in females. The present results indicate that juvenile nicotine taking may have implications for the endocannabinoid and endogenous opioid function and for the behaviors served by those systems, this includes possible modification of the response of adults to different psychotropic drugs, i.e. cannabis and morphine/heroin when taken later in life.

Animals↗
PubMed2006

Enhancement of endocannabinoid signalling during adolescence: Modulation of impulsivity and long-term consequences on metabolic brain parameters in early maternally deprived rats.

Pharmacological modulation of the endocannabinoid system is a novel but poorly explored field for potential therapy. Early maternal deprivation represents an animal model for specific aspects of neuropsychiatric disorders. This study explored whether a pharmacological manipulation of the endocannabinoid system at adolescence may restore altered phenotypes resulting from early maternal deprivation. Wistar male rats, maternally deprived for 24 h on postnatal day (PND) 9, were administered the fatty-acid amide hydrolase (FAAH) inhibitor URB597 (0, 0.1 or 0.5 mg/kg/day) for six days during adolescence (PND 31-43), while tested in the intolerance-to-delay task. Deprived (DEP) adolescent rats showed a trend for higher impulsivity levels and an increased locomotor response to novelty when compared to non-deprived (NDEP) controls. The low dose of URB597 effectively decreased impulsive behaviour specifically in DEP subjects. Moreover, long-term metabolic brain changes, induced by drug treatment during adolescence, were detected in DEP animals using proton magnetic resonance spectroscopy ((1)H MRS). Significant changes were only found within the hippocampus: N-acetyl-aspartate and total creatine were up-regulated by the low dose; glutamate and glutamate plus glutamine were conversely down-regulated by the higher dose. In summary, administration of URB597 during adolescence increased self-control behaviour and produced enduring brain biochemical modifications, in a model for neuropsychiatric disorders.

Amidohydrolases↗
PubMed2006

Increased ethanol intake after prenatal ethanol exposure: studies with animals.

This review analyses the most relevant studies in which ethanol intake was measured after prenatal exposure to the drug. Despite the variety in methodology, in most such studies this prenatal experience induced a higher consumption of ethanol. Several variables that may affect the expression of this phenomenon are discussed, such as gender, age at testing, period of ethanol exposure, ethanol dose and conditions during the test. The mechanisms proposed in all these studies to explain the increased ethanol intake effect are also discussed. Some of these mechanisms are related to the teratological effects of the drug on the neurochemical systems involved in the reinforcing effects of abuse drugs, as well as on the regulatory systems of stress response. Another explanation of this phenomenon is also proposed in terms of associative learning. Specifically, the increased ethanol intake effect may be the result of a conditioned preference for ethanol acquired by the fetus when exposed to the drug during the last days of gestation.

Age Factors↗
PubMed2006

Early adversity and alcohol availability persistently modify serotonin and hypothalamic-pituitary-adrenal-axis metabolism and related behavior: what experimental research on rodents and primates can tell us.

Early experiences have profound influences on individual developmental trajectories. For example alcohol exposure during central nervous system development relates to a number of pathological consequences in adulthood. An increased risk of developing psychiatric disorders, like major depression and impulse-control-related pathologies is associated with alcohol exposure during fetal life and/or during adolescence. Additionally, adverse life experiences occurring early in development may exacerbate these consequences, while impinging on the same neural systems affected by precocious alcohol exposure. Conversely, a protective and/or stimulating environment may mitigate these alcohol-related negative outcomes. Experimental research in animal models constitutes a primary source of information in understanding both functional and dysfunctional human adaptations to these events. In this review, a selection of rodent and primate studies shows that developmental ethanol exposure on the one hand, and environmental treatments aimed at modifying the mother-offspring interaction on the other hand, independently modulate similar neuro-endocrine systems. In particular, we discuss the effects that the above-mentioned independent variables exert on the hypothalamic-pituitary-adrenal (HPA)-axis and on brain serotonergic pathways. Experimental evidence indicates that pathological adaptations of these systems are valuable predictors of human neuro-behavioral abnormalities like depression, impaired impulse control and alcohol abuse. Finally, a working hypothesis is proposed, which combines primate and rodent studies aimed: (i) at studying functional and pathological individual development following early ethanol consumption, and (ii) at heading towards a better definition of potential intervention strategies.

Animals↗
PubMed2006

Delay aversion but preference for large and rare rewards in two choice tasks: implications for the measurement of self-control parameters.

BACKGROUND: Impulsivity is defined as intolerance/aversion to waiting for reward. In intolerance-to-delay (ID) protocols, animals must choose between small/soon (SS) versus large/late (LL) rewards. In the probabilistic discount (PD) protocols, animals are faced with choice between small/sure (SS) versus large/luck-linked (LLL) rewards. It has been suggested that PD protocols also measure impulsivity, however, a clear dissociation has been reported between delay and probability discounting. RESULTS: Wistar adolescent rats (30- to 46-day-old) were tested using either protocol in drug-free state. In the ID protocol, animals showed a marked shift from LL to SS reward when delay increased, and this despite adverse consequences on the total amount of food obtained. In the PD protocol, animals developed a stable preference for LLL reward, and maintained it even when SS and LLL options were predicted and demonstrated to become indifferent. We demonstrate a clear dissociation between these two protocols. In the ID task, the aversion to delay was anti-economical and reflected impulsivity. In the PD task, preference for large reward was maintained despite its uncertain delivery, suggesting a strong attraction for unitary rewards of great magnitude. CONCLUSION: Uncertain delivery generated no aversion, when compared to delays producing an equivalent level of large-reward rarefaction. The PD task is suggested not to reflect impulsive behavior, and to generate patterns of choice that rather resemble the features of gambling. In summary, present data do indicate the need to interpret choice behavior in ID and PD protocols differently.

Animals↗
PubMed2006

Paradoxical effects of prenatal acetylcholinesterase blockade on neuro-behavioral development and drug-induced stereotypies in reeler mutant mice.

INTRODUCTION: Epidemiological and experimental studies support a link between genetic and epigenetic factors in vulnerability to develop enduring neurobehavioral alterations. We studied the interplay between genetic vulnerability and the prenatal exposure to a neurotoxic compound. Chlorpyrifos, a potent and reversible acetylcholinesterase blocker used as a pesticide, and the "reeler" mouse, lacking the extracellular-matrix protein Reelin, were used. MATERIALS AND METHODS: Homozygous reeler (RL), heterozygous (HZ), and wild-type (WT) mice were prenatally exposed to chlorpyrifos-oxon (CPF-O), the active metabolite of chlorpyrifos, or to vehicle (prenatal controls) on gestation days 14-16, that is, during a peak period of neurogenesis in the cerebral cortex. The offspring was reared by the natural dam and tested during infancy and at adulthood for global consequences of the prenatal exposure. CONCLUSION: The results are consistent with complex interactions between genetic (reeler genotype) and epigenetic (prenatal exposure to CPF-O) factors. In the case of some "genetically modulated" parameters (ultrasound vocalization, amphetamine-induced locomotion, and stereotypy), exposure to CPF-O paradoxically reverted the effects produced by progressive reelin absence. Conversely, for an "epigenetically modulated" parameter (grasping reflex maturation), the effects of CPF-O exposure were counteracted by progressive reelin absence. Finally, for parameters apparently untouched by either factor alone (righting reflex latency, scopolamine-induced locomotor activity), prenatal CPF-O exposure unmasked an otherwise latent genotype dependency. This complex picture also points to reciprocal adaptations within cholinergic and dopaminergic systems during development. Data are interesting in view of recently discovered cholinergic abnormalities in autism and schizophrenia, and may suggest new avenues for early intervention.

Amphetamine↗
PubMed2006

Specific changes in levels of autoantibodies to glutamate and opiate receptors induced by morphine administration in rats.

Several groups of brain receptors are involved in the mechanisms underlying the development of opiate addiction, but the interactions occurring between these neuroreceptors and the immune system, including potential autoimmune responses, remain poorly understood. We studied in rats the effects of repeated administration of different psychotropic drugs on serum levels of autoantibodies (aAbs) to the mu delta-opiate receptor (MDOR), as well as to the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) GluR1 and to the N-methyl-D-aspartate (NMDA) NR2 subunits of the glutamate receptor, as analyzed by ELISA. We found that repeated administration of morphine significantly elevated aAbs levels to MDOR and to the AMPA GluR1 subunit, but not to the NMDA NR2 subunit. In contrast, a similar regimen of a psychostimulant drug, such as D-amphetamine, or a commonly abused substance, such as nicotine, had no effect on these aAbs levels. A nonspecific elevating effect on aAbs to the brain structural protein S100B was observed for all drugs tested versus controls. These observations support the hypothesis that, following opiate administration, specific interactions between nervous and immune systems occur. Therefore, together with further investigations on their potential functional consequences, we propose a thorough exploration of aAbs to MDOR and to AMPA GluR1 subunit as early biomarkers signaling opiate addiction.

Animals↗
PubMed2006

Long-term effects of neonatal basal forebrain cholinergic lesions on radial maze learning and impulsivity in rats.

We examined long-term behavioural effects of neonatal lesions of the cholinergic basal forebrain obtained by intracerebroventricular injections of 192 IgG saporin (192 IgG-Sap). Five-month-old Wistar male rats (injected with 192 IgG-Sap or phosphate-buffered saline on postnatal day 7) were tested using operant chambers with two nose-poking holes, delivering one food pellet immediately or five pellets after a delay. The length of delay progressively increased over days (from 0 to 100 s). When compared with controls, 192 IgG-Sap rats showed a slight preference for smaller immediate over larger delayed rewards, thus indicating elevated intolerance to delay (i.e. more impulsivity). Sibling animals were tested in a computerized radial maze (baited vs. nonbaited arm procedure). 192 IgG-Sap rats appeared slower than controls in accomplishing the task. The neonatal 192 IgG-Sap lesion did not alter cortical levels of serotonin and/or its metabolites, but induced a marked cortical cholinergic loss. Our data suggest that a prolonged basal forebrain cholinergic hypofunction produces (i) an impairment in cognitive performances that is detectable only when highly complex tasks are used; (ii) a slight enhancement of the impulsive behavioural profile. This animal model may thus be useful to investigate some cognitive deficits and other secondary symptoms seen in Alzheimer's disease.

Alzheimer Disease↗
PubMed2006

Motor impulsivity in APP-SWE mice: a model of Alzheimer's disease.

Among transgenic mouse models of Alzheimer's disease, APP-SWE mice have been shown to develop beta-amyloid plaques and to exhibit progressive impairment of cognitive function. Human Alzheimer's disease, however, also includes secondary clinical manifestations, spanning from hyperactivity to agitation. The aim of this study was a better characterization of motor impulsivity in APP-SWE mice, observed at 12 months of age, when levels of soluble beta-amyloid are elevated and beta-amyloid neuritic plaques start to appear. Mice were tested for spatial learning abilities in the Morris water maze (seven daily sessions, four trials per day). The distance traveled to reach the hidden platform showed a learning curve in both groups. This profile, however, was somewhat delayed in APP-SWE mice, thus confirming slightly impaired spatial capacities. To evaluate motor impulsivity, animals were trained to nose-poke for a food reward, which was delivered after a waiting interval that increased over days (15-60 s). Further nose-poking during this signaled waiting interval resulted in food-reward loss and electric-shock punishment. APP-SWE mice received an increased quantity of punishment and were able to earn fewer food rewards, suggesting inability to wait already at the lowest delay. After the animals were killed, prefrontal cortex samples were assessed for neurochemical parameters. Serotonin turnover was elevated in the prefrontal cortex of APP-SWE mice compared with controls. The results clearly confirm cognitive deficits, and are consistent with the hypothesis of reduced behavioral-inhibition abilities. Together with recent findings, APP-SWE mice emerge as a suitable animal model, characterized by a number of specific behavioral alterations, resembling primary and secondary symptoms of human Alzheimer's disease.

Alzheimer Disease↗
PubMed2006

Short-term effects of adolescent methylphenidate exposure on brain striatal gene expression and sexual/endocrine parameters in male rats.

Exposure to methylphenidate (MPH) during adolescence is the elective therapy for attention deficit/hyperactivity disorder (ADHD) children, but raises major concerns for public health, due to possibly persistent neurobehavioral changes. Rats (30- to 44-days old) were administered MPH (2 mg/kg, i.p once daily) or saline (SAL). At the end of the treatment we collected plasma, testicular, liver, and brain (striatum) samples. The testes and liver were used to evaluate conventional reproductive and metabolic endpoints. Testes of MPH-exposed rats weighed more and contained an increased quantity of sperm, whereas testicular levels of testosterone (TST) were markedly decreased. The MPH treatment exerted an inductive effect on enzymatic activity of TST hydroxylases, resulting in increased hepatic TST catabolism. These findings suggest that subchronic MPH exposure in adolescent rats could have a trophic action on testis growth and a negative impact on TST metabolism. We have analyzed striatal gene expression profiles as a consequence of MPH exposure during adolescence, using microarray technology. More than 700 genes were upregulated in the striatum of MPH-treated rats (foldchange >1.5). A first group of genes were apparently involved in migration of immature neural/glial cells and/or growth of novel axons. These genes include matrix proteases (ADAM-1, MMP14), their inhibitors (TIMP-2, TIMP-3), the hyaluronan-mediated motility receptor (RHAMM), and growth factors (transforming growth factor-beta3 [TGF-beta3] and fibroblast growth factor 14 [FGF14]). A second group of genes were suggestive of active axonal myelination. These genes mediate survival of immature cells after contact with newly produced axonal matrix (laminin B1, collagens, integrin alpha 6) and stabilization of myelinating glia-axon contacts (RAB13, contactins 3 and 4). A third group indicated the appearance and/or upregulation of mature processes. The latter included genes for: K+ channels (TASK-1, TASK-5), intercellular junctions (connexin30), neurotransmitter receptors (adrenergic alpha 1B, kainate 2, serotonin 7, GABA-A), as well as major proteins responsible for their transport and/or anchoring (Homer 1, MAGUK MPP3, Shank2). All these genes were possibly involved in synaptic plasticity, namely the formation, maturation, and stabilization of new neural connections within the striatum. MPH treatment seems to potentiate synaptic plasticity, which is an age-dependent developmental phenomenon that adolescent rats are very likely to show, compared to adults. Our observations suggest that adolescent MPH exposure causes only transient changes in reproductive and hormonal parameters, and a more enduring enhancement of neurobehavioral plasticity.

Animals↗
PubMed2006

[ADHD and multimodal intervention].

During the year 2003, the National Register of the Attention deficit hyperactivity disorder (ADHD) has been implemented in Italy. It was commissioned by the Ministry of Health to the Istituto Superiore di Sanità, which is its leading technical and scientific body, with the aim to set up a sound database gathering detailed information on the prescription of Ritalin at the national level. The latter represents the most diffused elective drug treatment for such an early-onset neuropsychiatric syndrome. To this aim, the more prevalent theories on the pathogenesis of ADHD and the debate on therapy are reviewed and discussed. This paper is aimed at emphasizing that this kind of systematic data gathering of such a Register has not to be meant an unconditional approval of a therapeutical approach based on drug therapy only. Pharmacological therapies may or may not be included within the frame of a multimodal complex treatment plan which should also rely on psychological intervention.

Attention Deficit Disorder with Hyperactivity↗
PubMed2005

Response to novelty, social and self-control behaviors, in rats exposed to neonatal anoxia: modulatory effects of an enriched environment.

Perinatal asphyxia is a concern for public health and may promote subtle and long-lasting neuropsychiatric disorders. In the present study, newborn Wistar rat pups underwent a repeated 20-min exposure to a 100% N2 atmosphere (or air) on postnatal days (pnd) 1, 3, 5, and 7. Half of the animals were housed during adolescence (pnd 21-35) in an enriched environment. The consequences on behavior were assessed throughout adolescence to adulthood. When scored for social performance, adolescent rats exposed to neonatal asphyxia exhibited exaggerated levels of anogenital sniffing behavior, which was normalized by enriched living. In air-exposed controls, enriched living increased the expression of affiliative and novelty-seeking behaviors, as compared to standard housing. However, this enrichment-induced behavioral plasticity was not found in rats neonatally exposed to asphyxia. At adulthood, levels of impulsivity and 5-HT2A receptors in the striatum were markedly increased in neonatal-asphyxia rats kept in standard-housing conditions. Interestingly, impulsivity and receptor density were normalized by enriched rearing during adolescence. These findings indicate profound long-lasting behavioral alterations as a consequence of repeated neonatal asphyxia in rats. Beneficial effects of stimulation by an enriched environment during the still-plastic window of adolescence are suggested in these animals.

Animals↗
PubMed2005

Methylphenidate administration to adolescent rats determines plastic changes on reward-related behavior and striatal gene expression.

Administration of methylphenidate (MPH, Ritalin) to children with attention deficit hyperactivity disorder (ADHD) is an elective therapy, but raises concerns for public health, due to possible persistent neurobehavioral alterations. Wistar adolescent rats (30 to 46 day old) were administered MPH or saline (SAL) for 16 days, and tested for reward-related and motivational-choice behaviors. When tested in adulthood in a drug-free state, MPH-pretreated animals showed increased choice flexibility and economical efficiency, as well as a dissociation between dampened place conditioning and more marked locomotor sensitization induced by cocaine, compared to SAL-pretreated controls. The striatal complex, a core component of the natural reward system, was collected both at the end of the MPH treatment and in adulthood. Genome-wide expression profiling, followed by RT-PCR validation on independent samples, showed that three members of the postsynaptic-density family and five neurotransmitter receptors were upregulated in the adolescent striatum after subchronic MPH administration. Interestingly, only genes for the kainate 2 subunit of ionotropic glutamate receptor (Grik2, also known as KA2) and the 5-hydroxytryptamine (serotonin) receptor 7 (Htr7) (but not GABA(A) subunits and adrenergic receptor alpha1b) were still upregulated in adulthood. cAMP responsive element-binding protein and Homer 1a transcripts were modulated only as a long-term effect. In summary, our data indicate short-term changes in neural plasticity, suggested by modulation of expression of key genes, and functional changes in striatal circuits. These modifications might in turn trigger enduring changes responsible for the adult neurobehavioral profile, that is, altered processing of incentive values and a modified flexibility/habit balance.

Animals↗
PubMed2005

Preexposure during or following adolescence differently affects nicotine-rewarding properties in adult rats.

RATIONALE: Many people come in contact with psychoactive drugs, yet not all of them become addicts. Epidemiology shows that a late approach with cigarette smoking is associated with a lower probability to develop nicotine dependence. Exposure to nicotine during periadolescence, but not similar exposure in the postadolescent period, increases nicotine self-administration in rats, but underlying mechanisms remain poorly understood. OBJECTIVE: We investigated whether exposure to nicotine during or after adolescence would alter rewarding properties of the same drug at adulthood, as assessed by place conditioning. MATERIALS AND METHODS: Periadolescent (PND 34-43) or postadolescent (PND 60-69) rats were injected with saline or nicotine (0.4 mg kg(-1)) for 10 days. The rats received three pairings with saline and three pairings with nicotine (0, 0.3, or 0.6 mg kg(-1)) 5 weeks after pretreatment. The rats were then tested for place conditioning in a drug-free state. RESULTS: Upon first exposure to the apparatus, animals pretreated with nicotine during adolescence showed elevated novelty-induced activation. The 0.3 (but not the 0.6) mg kg(-1) dose failed to produce both ongoing locomotor sensitization and place conditioning in animals pretreated with nicotine following adolescence. This suggests a rightward shift in the dose-response curve, namely, a reduced efficacy of nicotine. Conversely, the same dose was effective in saline-pretreated controls and noteworthy in rats pretreated during adolescence. CONCLUSION: Exposure following the adolescent period might diminish the risk to develop nicotine dependence. As for human implications, findings are consistent with a reduced vulnerability to nicotine addiction in people who start smoking late in their life.

Age Factors↗
PubMed2005

Aspects of spatial memory and behavioral disinhibition in Tg2576 transgenic mice as a model of Alzheimer's disease.

Transgenic mouse models of Alzheimer's disease (AD) have been recently advanced. Tg2576 mice have been shown to develop progressive beta-amyloid (Abeta) neuritic plaques and exhibit impairment of cognitive function. The aim of this study was a better characterization of different aspects of spatial memory performance of transgenic mice, observed at a time when levels of soluble Abeta are elevated and Abeta neuritc plaques start to appear. A general elevation of basal locomotory activity in the home cage was found in Tg2576 mice, which also exhibited an impairment of spontaneous alternation in the Y-maze test. Tg2576 mice were not flexible upon changes in the schedule and failed to codify spatially the testing environment. Consistently, a deficit of spatial memory was also observed when mice were assessed for levels of reactivity to spatial change in the modified open-field test with objects. Compared to controls, Tg2576 mice also exhibited an increased number of explorative approaches to the different objects, and failed to discriminate the displacement of the object. Consistently with the hypothesis of increased disinhibition, a differential behavioural response to the plus-maze paradigm was exhibited by Tg2576 mice. Results clearly indicate that Tg2576 mice are characterized by a number of specific behavioral cognitive alterations, compatible with Alzheimer's disease (AD), which make them a suitable animal model for testing of novel anti-AD drugs.

Alzheimer Disease↗