Biomedical subjects

E Alleva

Publications and source records attributed to E Alleva.

At least 91 records · Page 5Linked to original sources

PubMed1994

NGF effects on hot plate behaviors in mice.

Adult CD-1 male mice were injected intravenously with 2.5 micrograms/g of highly purified murine NGF and then assessed for hot plate responding (52 degrees C) at 15, 30, 60, 180, and 360 min (repeated test) or at 30, 60, or 360 min (single test, i.e., exposure to hot plate only once). Control animals received cytochrome c (2.5 micrograms/g). In the repeated test, NGF produced hyperalgesia, increasing the number of jumps (particularly at 30 and 60 min postinjection), while in the single test the pain reaction of NGF-treated animals remained unaffected. Sensitization of C-fibers in the periphery or release of bioactive mediators from mast cells may account for NGF-induced changes in nociception.

Animals↗

PubMed1994

Induction of maternal behavior by mouse neonates: influence of dam parity and prenatal oxazepam exposure.

The aim of the present report was to investigate the influence of pup stimulus properties and female parity on mouse maternal behavior. Outbred CD-1 mouse pups, prenatally exposed to either the vehicle (VEH) or oxazepam (OX, 15 mg/kg twice/day on pregnancy days 12-16) and fostered to untreated dams at birth, were offered as a stimulus on postnatal days 4, 6, and 8 to four groups of females that differed in maternal experience: virgin, experienced virgin females, primiparae, and biparae. Maternal behavior was observed during a 15-min session each day. Virgin females were less involved in crouching behavior than primiparae. Pups, age, and prenatal oxazepam showed interactive effects on maternal care, particularly by increasing licking and nest-building activities and decreasing still-out behavior. Moreover, dams receiving younger pups showed high levels of both locomotor activity and rearing. The present findings point to the need for a better understanding of mother-pup interactions in studies aimed at characterizing drug and toxicant effects on both animal and human development.

Animals↗

PubMed1994

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↗

PubMed1994

Cold water swimming stress alters NGF and low-affinity NGF receptor distribution in developing rat brain.

We have previously shown that the nerve growth factor (NGF) is released into the bloodstream following intraspecific fighting behaviour and that the level released correlates with the number of fighting episodes. We subsequently reported that NGF and its messenger RNA are present in identified hypothalamic nuclei and increase following intermale fighting behaviour. This report provides data showing that in 16-day-old rats cold water swimming stress (CWSS) alters the distribution of low-affinity NGF-Receptors (p75NGFR) and NGF levels in the central nervous system. A significant increase of NGF level was observed in the cortex, while the p75NGFR immunoreactivity decreased in neurons of the septum, nucleus basalis and striatum. Choline acetyltransferase activity in forebrain tissues remained at baseline levels. Our result suggests that NGF and p75NGFR, involved in the development and differentiation of the nervous system, are affected by stress.

Animals↗

PubMed1994

Effects of repeated administrations of EGF and TGF-alpha on mouse neurobehavioral development.

In this study we tested the effects of repeated administrations of Epidermal Growth Factor (EGF) and Transforming Growth Factor-alpha (TGF-alpha) on mouse pups' neurobehavioral development. Each subject was injected subcutaneously with either EGF or TGF-alpha on postnatal days 2, 4, 6, 8, and 10. Pups treated with these two peptides showed accelerated eyelid opening and eruption of the lower incisors when compared to Cytochrome c-injected control littermates. EGF, but not TGF-alpha, resulted in a slight body growth retardation. When scored for a number of neurobehavioral parameters, EGF pups showed a delayed appearance of the righting reflex. Also, EGF-treated pups exhibited greater ultrasonic vocalization calling rates than controls when tested on postnatal day 7. Overall, TGF-alpha administration resulted in minor effects, when compared with EGF treatment, probably as a result of the lower dose administered (EGF: 3.5 mg/kg vs TGF-alpha: 1 mg/kg). TGF-alpha affected pups' eyelid opening and incisor eruption, similarly to EGF, but seemed to exert an opposite effect on some neurobehavioral scores, in line with what was already reported for Nerve Growth Factor (NGF) (Calamandrei and Alleva, 1989). These results confirm the role played by polypeptide growth factors on mammalian physical and neurobehavioral development and suggest that TGF-alpha might affect mouse brain development in a similar fashion as NGF.

Animals↗

PubMed1994

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↗

PubMed1993

Ontogeny of amicable social behavior in the mouse: gender differences and ongoing isolation outcomes.

The behavioral repertoire of male and female outbred CD-1 mice was characterized during development (postnatal Days 23-47). To assess the effects of the rearing condition, half of the subjects were individually housed (IC) at weaning (Day 21), while the remaining mice were housed in pairs (PC) of same-sex siblings. The occurrence of 22 behavioral items was scored during nine social encounters, 3 days apart, between pairs of unfamiliar same-sex and same-condition animals. Individually housed mice were much more involved than paired subjects in solitary play and social interactions (affiliative, investigative, and soliciting behaviors), while less interested in nonsocial behaviors (exploration, and escape-oriented or maintenance activities). An over-days increment for elements of social behavior was evident, with a peak of affiliative behavior at 23-32 days of age. For gender differences, in contrast with rat data, a marked female primacy in both social and playful behaviors was found. Overall, these findings clearly indicate that the behavioral repertoire of developing mice during paired encounters is strongly affected by both the sex of the subjects and the housing condition they are experiencing.

Animals↗

PubMed1993

Impaired acquisition of swimming navigation in adult mice exposed prenatally to oxazepam.

Prenatally administered oxazepam (OX) impairs adult radial maze performance in mice, possibly by permanent hippocampal changes. CDI mice were tested in swimming navigation, a sensitive indicator for hippocampal damage. Ten males and ten females were exposed to OX on fetal days 12-16 by maternal administration PO of 30 mg/kg/day and fostered at birth to untreated dams, while control mice received vehicle solution. All mice were tested at 8-9 weeks for ability to find a submerged platform in a fixed location (acquisition: 18 trials, 6 trials per day) and for capacity to re-orient towards a new platform position (reversal: 12 trials, 6 trials per day). OX mice showed a slight but significant impairment of swimming navigation during the initial part of training, as indicated by longer swimming paths during the fourth and fifth trial (day 1), an impairment due both to delayed habituation to the novel stressfull condition and acquisition of platform climbing but unrelated to navigational abilities. No treatment-dependent differences were observed in the reversal phase. During reversal, both OX and control females spent significantly more time in swimming across the location of the old platform. Unrelated to navigational performance, females showed a slightly but significantly higher swimming speed than males. Due to the absence of any navigational impairment, data suggest that prenatal exposure to oxazepam exerts long-term influence on adult learning capacities primarily through interaction with brain systems located outside the hippocampus.

Animals↗

PubMed1993

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↗

PubMed1993

Neonatal capsaicin exposure affects isolation-induced aggressive behavior and hypothalamic substance P levels of adult male mice (Mus musculus).

Subcutaneous administration of capsaicin (50 mg/kg) at Postnatal Days 2 and 5 exerted long-term effects on isolation-induced aggressive behavior of adult mice (Mus musculus) of the CD-1 strain. Isolated capsaicin-treated mice (scored during a 10-min session) showed the highest frequency and the longest duration of total attacks, attacks, rattling, and offensive upright posture when compared with nonisolated capsaicin-treated subjects and both isolated and nonisolated vehicle control animals. Hypothalamic Substance P (SP) was assessed by radioimmunoassay. Capsaicin treatment significantly lowered hypothalamic SP content in both isolated and nonisolated mice. Moreover, individual scores of isolated capsaicin-treated subjects showed a significant correlation between SP depletion and expression of offensive upright posture. Isolation per se was revealed to play an important role in depleting SP from the hypothalamus.

Aggression↗

PubMed1993

Familiarity with conspecific odor and isolation-induced aggressive behavior in male mice (Mus domesticus).

Male Swiss CD-1 mice (Mus domesticus, n = 60) were isolated for 24 days. In the isolation group mice were exposed to their own odor; in the familiarity group mice were familiarized with pairmates' odor by daily exchange of bedding; and in the unfamiliarity group subjects (exposed) were familiarized with pairmates' odor, whereas the pairmates (nonexposed) were familiarized with odors of other isolated mice. Aggressive behavior was scored during 20-min sessions. Familiarity with the pairmate's odor (familiarity and exposed subgroups) caused an enhancement of aggressive behavior, shown by the highest frequency of tail rattling and offensive upright posture and by a decrease in latency to the 1st attack. Nonexposed subjects showed high values of submissive upright posture, screaming, fleeing, and freezing. The results suggest that dominantlike behavior, acquired in social isolation, may be directed toward a conspecific whose odor is familiar.

Aggression↗

PubMed1993

Growth factors in behavioral teratology.

Polypeptide Growth Factors are protein molecules which regulate cell proliferation and/or differentiation. A number of different Growth Factors (GFs) have been identified and characterized in recent years, and they have been shown to control several physiological processes, such as growth, repair, differentiation, and development of specific cell populations. In particular Nerve Growth Factor, the best characterized among the about 30 GF molecules, is endowed with specific activities on cholinergic and peptidergic CNS neurons. Several GFs originally named according to their biological activity (Epidermal Growth Factor, EGF; Fibroblast Growth Factor: FGF; Transforming Growth Factor: TGF; Insulin-like Growth Factor: IGF) have been recently found in the central nervous system. The effects of in vivo GF administration on the ontogenesis of altricial rodents are reported. Indexes of neurobehavioral maturation are accelerated upon neonatal NGF and bFGF exposure, while a similar treatment with EGF exerts both growth-promoting and growth-inhibiting effects on mouse somatic and behavioral development. Administration of IGF appears to affect ultrasonic vocalization in mouse pups. Moreover, NGF given intracerebroventricularly to newborn mice anticipates both the appearance of the scopolamine-induced hyperactivity and the maturation of behaviours under cholinergic control. The present findings are in agreement with a model where different GFs can "switch on" developmental events leading sometimes to dramatic changes in the normal ontogenetic pattern.

Age Factors↗

PubMed1993

Morphine administration or sexual segregation in infancy affect the response to the same drug in adult mice.

Several experiments indicate that CNS opioid regulatory systems show a remarkable plasticity during development. The same systems respond to a wide range of environmental stimuli, particularly those which can affect the threshold of pain sensitivity (e.g., Environmentally Induced Analgesia). This paper summarizes a series of studies using outbred CD-1 mice, aimed at assessing: a) morphine effects on pain sensitivity and locomotor activity at two ages during development, namely, before and after weaning, and b) the consequences of such exposure on adult sensitivity to the same drug. The development of hot-plate response consisted mainly of a progressive decrease of latencies and of a parallel reduction of sensitivity to morphine. While morphine depressed activity on day 14, it increased or had apparently no effect on day 21. With respect to carry-over consequences of early drug and test exposure, the animals with a history of testing at the preweanling stage were more sensitive to the depressant effect of morphine (10 mg/kg) than those pretested at a later stage. By contrast, morphine analgesia was attenuated by drug pre-exposure, independently of the age of previous testing. In sum, the age of early exposure and type of early treatment interacted to determine the level of adult pain sensitivity in the no-drug state. Finally, the long-term effects of sexual segregation in infancy on the response to painful stimulation and morphine were assessed. Adult male mice-reared from birth to weaning in litters containing either only male pups (MM), or both male and female pups (MF)--were challenged in a hot-plate test upon morphine or saline injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1992

Ontogeny of cocaine hyperactivity and conditioned place preference in mice.

Conditioned place preference (CPP) procedures using jointly visual and tactile cues (white compartment with a wide-mesh metal floor versus black compartment with a narrow-mesh floor) were employed to assess the ontogenetic pattern of cocaine reinforcing properties in outbred CD1 mice. A classical 11-day-long schedule, in which the drug experience occurred in the initially less-preferred compartment ("biased" procedure, Spyraki 1988), served to study cocaine (0, 1, 5, or 25 mg/kg IP repeated four times at 48 h intervals) during the early postweaning stage (21-32 days). The result was a fully-fledged CPP at all cocaine doses. A subsequent experiment used a shortened (4-day) "unbiased" CPP schedule (animals assigned at random to drug experience in one or the other compartment); this enabled an assessment of the ontogenetic pattern of the drug action (single treatment, same dose range) in pups of both sexes at three different developmental ages (14-17, 21-24, or 28-31 days). At the 25 mg/kg dose, CPP developed in animals of all ages, while the 5 mg/kg dose was effective only in 21-24 day pups and the 1 mg/kg dose was ineffective. No significant sex differences were found, but the use of the unbiased procedure enabled a demonstration of an interaction between treatment, age, and type of CS. At the preweaning stage, CPP was due mainly to an increased preference for the black/narrow-mesh compartment, while at the early postweaning stage it consisted mainly of an increased preference for the white/wide-mesh compartment; at the late postweaning stage the cue and the treatment factor did not interact.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1992

NGF decreases isolation-induced aggressive behavior, while increasing adrenal volume, in adult male mice.

Intravenous administration of highly purified murine nerve growth factor (NGF, either 15 or 30 micrograms/subject/day) for six consecutive days to adult male mice of the CD-1 strain markedly influenced a number of items of aggressive behavior induced by 5 weeks of individual housing. Control mice received the same doses of cytochrome c. During a 20-min fighting session on day 7, both NGF-treated groups showed longer Latency to the first Attack, while Total Attacking Time and Aggressive grooming were significantly lower when compared to control animals. Twenty-four h later, adrenals from the NGF- and cytochrome c-treated groups were dissected and analyzed by means of a Vidas Image-Analyzer. NGF administration produced a remarkable dose-dependent increase in both adrenal weight and volume (particularly in the medullary zone), supporting the hypothesis that adrenals represent a possible target for the NGF release from submaxillary salivary glands occurring upon intraspecific fighting.

Adrenal Glands↗

PubMed1992

Selective changes in mouse behavioral development after prenatal benzodiazepine exposure: a progress report.

1. Animal studies of the effects of early exposure to CNS agents devoid of a major teratogenic potential must assess possible deviations from normal behavioral development in both a stage-specific and a behavior-specific fashion; several experiments on prenatal benzodiazepine (BDZ) exposure are reviewed, illustrating such an assessment strategy and discussing caveats on experimental designs and statistical analysis. 2. The offspring of mouse dams treated in late pregnancy with oxazepam (15 mg/kg p.o. twice daily on days 12-16) show a mild and reversible impairment in somatic and neurobehavioral development which is unlikely to be responsible for a series of other more specific changes. 3. The treatment produces a selective reduction of locomotor activity and amphetamine hyperactivity at the end of the second postnatal week, as well as a selective impairment of active avoidance at the young adult stage, in the absence of similar changes in scopolamine hyperactivity and passive avoidance. 4. The treatment also prevents the appearance at 28 days of morphine hyperactivity and of rebound hyperactivity after muscimol depression, without modifying the developmental profile of pain reactivity and of morphine and muscimol analgesia. 5. Young adult females previously exposed to oxazepam in utero show a marked enhancement of maternal aggression towards male intruders; mother-pup interactions are also modified, leading either to reduced or to exaggerated maternal care as a function of fostering procedures. 6. Overall, several effects of prenatal BDZ exposure appear to be amenable to modifications in monoaminergic system functions and/or to an accelerated development of GABAergic mechanisms; some of the changes in social and parental interactions, however, point to subtle modifications in the balance between different components of the fear-defensive repertoire, possibly due to an altered stimulus reactivity by mechanisms which are still poorly understood.

Animals↗

PubMed1992

Eight-arm maze performance, neophobia, and hippocampal cholinergic alterations after prenatal oxazepam in mice.

Outbred CD-1 mice were exposed to oxazepam (15 mg/kg PO twice/day) on days 12-16 of fetal life, i.e., at a critical ontogenetic stage of Type II benzodiazepine (BDZ) receptor increase, and fostered at birth to untreated dams. At adulthood, radial arm maze performance, activity-habituation test in an open-field arena (either single 15-min test or three 5-min sessions at 24-h intervals), approach to a novel stimulus object, and amphetamine or scopolamine effects thereon were assessed in male progeny. Overall, the oxazepam exposed (OX) mice were much less efficient in the radial arm maze task than the vehicle exposed (VEH) animals. Pre-test scopolamine injection, but not amphetamine, significantly impaired the arm maze performance of OX mice when compared with the corresponding VEH-scopolamine animals. In separate nonlearned behavioral tasks, prenatal oxazepam did not affect either baseline activity levels in the open field or the response to the amphetamine and the scopolamine challenge, while it considerably increased the latency of first approach to a novel object and produced a deficit of habituation in the course of the subsequent exploratory period. Concomitant investigation at the neurochemical level showed that the adult OX animals had a significant increase in both Bmax and in the affinity (Kd) of cholinergic muscarinic receptors in the hippocampal formation when compared to the vehicle-exposed controls.

Amphetamine↗

PubMed1992

Developmental aspects of neurobehavioural toxicity.

Previous work on the developmental aspects of neurobehavioural toxicity in rats and mice has shown the reliability of a variety of procedures aimed at assessing changes that may have widespread functional consequences, for example: (i) modified Fox batteries to study the maturation of various reflexes and responses after birth, (ii) activity/habituation and analgesia tests with age-specific profiles of reactivity to selected drug challenges, and (iii) simple learning tasks such as active and passive avoidance [1]. We will now summarize more recent work on other portions of the behavioural repertoire which deserve to be thoroughly assessed in "higher-tier" studies.

Aggression↗