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Biomedical subjects

L Ricceri

Publications and source records attributed to L Ricceri.

16 recordsLinked to original sources

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

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

Animals↗

The acallosal mouse strain I/LnJ: a putative model of ADHD?

ADHD has been sometimes associated to a defective interhemispheric cross-talk caused by hypoplasia of the corpus callosum. The inbred mouse strain I/LnJ shows total callosal agenesis with complete penetrance, and behavioral features which resemble ADHD. In conditioned learning tasks, as well as in paradigms of spontaneous behavior. I/LnJ mice, as compared to other inbred strains, show lower learning scores, impulsiveness, and significantly higher locomotor activity, albeit with considerable individual variations. In order to disentangle the influences of the genetic background from the effects of the callosal agenesis, we undertook crossing studies between I/LnJ and C57BL/6 mice, obtaining hybrids with missing corpus callosum. In comparison to normal C57BL/6 mice, acallosal hybrids exposed to a novel open-field showed a different locomotor pattern, with less short stops and more center crossing during the beginning of the session. In a metabolic mapping study, the tendency of acallosals to stay off the walls was found to be associated to lower 2-deoxyglucose uptake in the left striatum and cerebral cortex, while the number of short stops was correlated to the bilateral levels of 2-deoxyglucose uptake in the frontal and parietal cortex. The results hint at a right hemisphere dominance in impulsiveness and hyperactivity, boosted by the lack of callosal connections.

Agenesis of Corpus Callosum↗

Temporal and spatial adaptation to food restriction in mice under naturalistic conditions.

Free-living female laboratory mice, adapted to outdoor life in large pens providing a naturalistic environment, were tested for their ability to modify their foraging habits to controlled food supply. An automatic feeder box delivered a small portion of the daily quantity of seeds to each individual mouse. Eight such boxes were placed into an outdoor pen. Each day, mice had to visit all boxes to gather the daily amount of food and were rewarded only at the first visit to each box. Mice were individually recognised by an implanted microchip. Throughout a 16-day period, feeding activity concentrated in an interval time around the beginning of the daily session. During the same period, the number of different feeders visited every day by mice increased irrespective of variation in exploratory activity. The experimental set-up allowed detecting temporal and spatial adaptations to the food restriction, as well as behavioural differences due to territorial and social factors. These data permit the design of novel tests assessing behavioural changes, memory and learning in normal and genetically modified mice, both in the laboratory and in naturalistic settings.

Adaptation, Psychological↗

Neonatal 192 IgG-saporin lesions of basal forebrain cholinergic neurons selectively impair response to spatial novelty in adult rats.

The role of the developing cholinergic basal forebrain system on cognitive behaviors was examined in 7 day-old rats by giving lesions with intraventricular injections of 192 IgG-saporin or saline. Rats were subjected to passive avoidance on postnatal days (PND) 22-23, water maze testing on PND 50-60, and a open-field test (in which reactions to spatial and object novelty were measured) on PND 54. Behavioral effects of the lesions were evident only in the open-field test with 5 objects. Unlike controls, the lesioned rats did not detect a spatial change after a displacement of 2 of the 5 objects. Control and lesioned rats, however, showed comparable novelty responses to an unfamiliar object. Lesion effectiveness was confirmed by 75% and 84% decreases in choline acetyltransferase activity in cortex and hippocampus. These results suggest that the developing cholinergic system may be involved in spatial information processing or attention to spatial modifications.

Animals↗

Neurobehavioral development, adult openfield exploration and swimming navigation learning in mice with a modified beta-amyloid precursor protein gene.

The processing of beta-amyloid precursor protein (betaAPP) and its metabolites plays an important role in the pathogenesis of Alzheimer's disease (AD) and Down's syndrome. The authors have reported elsewhere that a targeted mutation resulting in low expression of a shortened betaAPP protein (betaAPP(delta/delta)) entails reduced learning abilities. Here the authors investigate whether these effects were caused by postnatal developmental actions of the altered protein. The authors examined 35 mice carrying the betaAPP(delta/delta) mutation for somatic growth and sensorimotor development during the first 4 postnatal weeks (pw) and compared them with 31 wildtype litter-mates. Thereafter, the same mice were tested at about 10 weeks of age for openfield behavior and for swimming navigation learning. Mutant mice showed both transient and long-lasting deficits in development. Body weight deficit started to emerge at postnatal day (pd) 12, peaked with a 15.1% deficit at pd 27 and lasted until pw 33-37. Significant transient deficits in mutant mice during sensorimotor development were observed in three time windows (pd 3-10, pd 11-19 and pd 20-27), long-lasting effects, manifest at pw 8-12 and pw 33-37, emerged at any of the three periods. In the adult mice, exploratory activity of betaAPP mutants in the openfield arena was severely reduced. In the Morris water maze task, mutant mice showed moderate escape performance deficits during the acquisition period but no impairment in spatial memory. The authors conclude that a defective betaAPP gene impairs postnatal somatic development, associated with transient as well as long-lasting neurobehavioral retardation and muscular weakness. Comparison with earlier data suggests that early postnatal handling may attenuate some of the non-cognitive performance deficits in the water maze. Further, the manifestation and time course of behavioral yet not neuropathological symptoms in betaAPP mutant mice resemble in some aspects those of the human Down's syndrome.

Adult↗

Postnatal choline supplementation in preweanling mice: sexually dimorphic behavioral and neurochemical effects.

The aim of this study was to investigate the effects of postnatal choline supplementation on neurochemical and behavioral parameters in preweanling BALB/cByJ mice. Mouse pups were injected daily subcutaneously with choline chloride (0.85 mM/g body weight) from Postnatal Day (PND) 1 to PND 16. Pups performed a passive avoidance (PA) learning task on PND 17-18 and a 30-min locomotor activity test on PND 19. The choline treatment affected retention of the PA task on PND 18. The treatment also increased locomotor activity in females, but not in males, on PND 19. Choline acetyltransferase (ChAT) enzymatic activity was measured on PND 20 and revealed that choline administration in the first 2 weeks of postnatal life selectively affects male pups. Choline's effect, as seen in previous rat experiments, was to decrease ChAT activity in the hippocampal region.

Animals↗

Sexually dimorphic effects of anti-NGF treatment in neonatal rats.

This study investigated how chronic perinatal reduction of nerve growth factor (NGF) affected brain cholinergic markers in the two sexes. Rats received anti-NGF on postnatal days (PNDs) 2-12, and choline acetyltransferase (ChAT) activity was measured on PND 16. Anti-NGF significantly reduced cortical ChAT activity in males, but not in females; no sex-dependent effects were found in hippocampus or striatum. These data suggest sexual dimorphism in cholinergic responsiveness to NGF.

Animals↗

Neonatal cocaine alters behavioural responsiveness to scopolamine and cholinergic development in mice.

CD-1 mice received daily subcutaneous injections of either cocaine (20 mg/kg or 40 mg/kg) or saline solution (0.9% NaCl) from postnatal days 2 to 15. Pups were tested on days 16-17 for learning and 24-h retention of a passive avoidance task, where entering a dark compartment was punished with a mild foot shock. Locomotor activity and general behaviour in an open field arena were assessed on day 21, following administration of either the muscarinic blocker scopolamine (0.8 mg/kg) or saline solution. In addition, immunostaining for the enzyme choline acetyltransferase (ChAT) was measured in different basal forebrain areas (medial septum, striatum, and nucleus basalis) on day 30. Cocaine treatment failed to affect either learning or retention capabilities. Nonetheless, neophobic behaviour during the learning session was enhanced in control nonpunished mice exposed to the 20-mg/kg dose. In the open field test, although baseline activity levels were unaffected by cocaine exposure, the 40-mg/kg cocaine-treated pups showed decreased sensitivity to the hyperkinetic effects of scopolamine. ChAT immunocytochemistry revealed a significant reduction of the number of ChAT-immunopositive neurons in the nucleus basalis but not in the other cholinergic basal forebrain regions.

Animals↗

Different effects of postnatal day 1 versus 7 192 immunoglobulin G-saporin lesions on learning, exploratory behaviors, and neurochemistry in juvenile rats.

Passive avoidance learning and retention, as well as locomotor and exploratory behaviors, were assessed in rats after intraventricular 192 immunoglobulin G-saporin injections on either Postnatal Day 1 (PND1) or PND7. PND1-lesioned rats were not significantly impaired on acquisition or retention of passive avoidance. PND7-lesioned rats acquired the task slower than controls, but retention was not affected. PND7-lesioned rats were less exploratory than controls and showed reduced wall rearing. Histological analysis of PND1- and PND7-lesioned rats revealed no neuronal degeneration in hippocampus or cortex. There was a marked reduction of choline acetyltransferase (ChAT) activity in the hippocampus, cortex, and septum in the PND7-lesioned rats and a slight but significant ChAT depletion in the cortex of PND1-lesioned rats. These data suggest that the cholinergic system is critical for the learning of passive avoidance and exploratory behaviors in the developing rat.

Animals↗

Systemic administration of anti-NGF antibodies to neonatal mice impairs 24-h retention of an inhibitory avoidance task while increasing ChAT immunoreactivity in the medial septum.

Neonatal mice received subcutaneous injections of either antibody against murine NGF raised in goat (3 mg, injection volume 50 microliters) or preimmune serum on postnatal days 2, 4, 6, 8, 10, and 12. They were tested on postnatal days 15-16 or 20-21 for learning and 24-h retention of a passive avoidance step-through task. Immunostaining for choline acetyltransferase (ChAT) was measured in two cholinergic forebrain areas (septum and caudate-putamen) on postnatal day 16 or 21. Locomotor activity and exploratory behavior in an open-field test were also assessed on day 17 or 22, following a single administration of either scopolamine (2 mg/kg) or saline solution. While anti-NGF treatment did not affect acquisition on day 15, impairment in retention was evident on day 16. On days 20-21, no effects were found either on acquisition or on retention capabilities. Analysis of ChAT immunostaining revealed a significant increase of ChAT-immunopositive cells in the medial septal area in 16-day-old but not in 21-day-old mice. Behavior in the open-field test and age-typical response to scopolamine were not altered by anti-NGF at either of the two ages considered. These data support the view that immunological neutralization of endogenous NGF specifically affects the maturation of retention capabilities in altricial rodents, and confirm the involvement of forebrain cholinergic mechanisms in early memory processes.

Aging↗

Nerve growth factor affects passive avoidance learning and retention in developing mice.

The present studies investigate the effects of early nerve growth factor (NGF) administration on the ontogenetic profile of learning and retention capacities in mice. The learning paradigm used required the animals to withhold an escape response from a vibrating platform to avoid a punishment (step-down passive avoidance). In Experiment 1, acquisition of step-down passive avoidance was essentially the same in 11- and 15-day-old mice whereas only the latter showed significant retention after 24 h. In younger animals, data pointed to a facilitating effect of familiarization with the test environment. In Experiment 2 ICV NGF treatment on postnatal day 9 increased step-down latencies in both reinforced and nonreinforced pups on day 11. Moreover, NGF mice exposed in nonreinforcement condition on day 11 failed to acquire the avoidance response 24 h later, suggesting that the treatment anticipated the appearance of latent inhibition. Results of Experiment 3, investigating the effects of different durations of preexposure to the test apparatus on passive avoidance acquisition 24 h later, supported the specificity of NGF effects on the emergence of latent inhibition. These findings suggest that neural populations responsive to NGF trophic effect are involved in the maturation of early learning and retention capacities in rodents.

Animals↗

Impairment of passive avoidance learning following repeated administrations of antibodies against nerve growth factor in neonatal mice.

CD-1 Swiss mice were used to study the effects of repeated intracerebroventricular (i.c.v.) injections, on postnatal days (PND) 3, 6, 9, of rabbit antiserum (50 micrograms) raised against murine nerve growth factor (NGF) both on locomotor activity in an open field test (PND 10) and on a passive avoidance learning test (PND 11 and 12). While no difference was evident in locomotor activity levels between anti-NGF and control pups, an impairment of anti-NGF pups was detectable in the passive avoidance performance. Removal of endogenous NGF seems to produce a detrimental effect on a behavioural performance which is known to be under central cholinergic control, confirming previous reports on the role of NGF in early neurobehavioural responding in altricial rodents.

Acetylcholine↗

Prenatal oxazepam affects passive avoidance performance of preweaning mice.

CD-1 outbred mice were exposed to oxazepam on fetal days 12-16 by maternal administration (per os of 15 mg/kg twice daily at 8 a.m. and 8 p.m.) and fostered at birth to untreated dams, while control mice received vehicle solution. Mice were then tested on postnatal day 14 and 15 in a passive avoidance apparatus for their ability to withhold a step-down response from a vibrating platform. The step-down response was punished with a mild footshock. Each animal was subjected to a maximum of 15 trials. Mice prenatally treated with oxazepam showed an impairment in the acquisition of the task as indicated by shorter latencies to step-down throughout the 15 trials in both sessions (days 14 and 15). As control nonreinforced animals prenatally treated with oxazepam did not show a similar alteration in latency to step-down, these data suggest that prenatal exposure to oxazepam influences behavioral performance of preweaning mice in an aversively motivated task.

Animals↗

Effects of acute and continuous ozone (O3) exposure on activity/exploration and social behavior of CD-1 mice.

This study was aimed at investigating the behavioral effects of ozone (O3) exposure in CD-1 mice. Pairs of same-sex adult male and female mice were continuously exposed for 13 days to either 0, 0.4, 0.8, or 1.2 ppm O3. The exposure apparatus consisted of a system for O3 production and delivery into four stainless-steel chambers, each equipped to contain up to 24 home cages, with continuous monitoring and recording of concentrations. Acute behavioral changes were assessed during the first hour of O3 exposure without removing animals from the chambers. The onset of exposure produced remarkable behavioral disturbances consisting of a sharp increase of several responses (rearing, sniffing, grooming, feeding, and social interactions) paralleled by a reduction of bar-holding. These changes were rapidly reversed within 1 hour, suggesting that they constituted a response to strong novel stimulation followed by habituation. Subsequently, brief sessions of videorecording of the animals' activities in freshly cleaned cages (identical to the home cages) were performed outside the chambers after 3, 7, and 10 days of exposure. These tests showed a significant concentration-dependent increase of grooming and rearing and a decrease of crossing and wall climbing. Both food and water intake showed a nonmonotonic trend over time consisting of a concentration-dependent depression (for about 3 and 7 days, respectively) followed by recovery; body weight followed a similar trend. The detailed study of various components of the animal's behavioral repertoire, showing concentration-dependent and time-dependent changes in different directions, appears to be a sensitive tool in the analysis of pollutants' effects.

Air Pollutants↗

Postnatal cocaine exposure affects neonatal passive avoidance performance and cholinergic development in rats.

Wistar rat pups received either cocaine HCl (25 mg/kg) or saline (0.9% NaCl) SC from postnatal days 1-11. On days 12 (acquisition) and 13 (retention), they underwent a passive avoidance task (step-off response; grid foot-shock at 0.35 mA). Slight deficits were found in cocaine-treated subjects for latency to step-off during acquisition and for generalized increase in the number of trials to criterion in retention. On postnatal day 13, the level of choline acetyltransferase (ChAT) enzymatic activity and the distribution of ChAT neuronal immunoreactivity in forebrain structures were examined. These morphometric and biochemical studies demonstrate a decrease of cholinergic enzymes in the septum, while the remaining basal forebrain cholinergic regions were unaffected.

Animals↗

Neonatal exposure to anti-nerve growth factor antibodies affects exploratory behavior of developing mice in the hole board.

The aim of this study was to assess in developing mice whether the neutralization of endogenous NGF following ICV administration of anti-NGF antibodies (50 micrograms/2 microliters) on postnatal days 3, 6, 9, and 12 affected locomotor activity, exploratory behavior, and response to the cholinergic blocker scopolamine. In Experiments 1 and 2 activity and age-typical scopolamine effects were evaluated on PND 13 or 17 in an automated apparatus. No significant main effect of anti-NGF treatment was found at either age. On day 13 scopolamine (0.2, 1, or 2 mg/kg) decreased locomotion in both anti-NGF and control animals. In Experiment 3, locomotion and exploratory behavior were analyzed in an open field arena or in a hole board apparatus on PND 16. No significant effects of anti-NGF treatment on general motor activity and investigation of a novel object in the open field was found, though anti-NGF animals tended to be less active than controls. In the hole board anti-NGF pups showed a different pattern of head dipping behavior from controls, exploring mainly the holes located in the periphery of the apparatus.

Animals↗