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G Laviola

Publications and source records attributed to G Laviola.

At least 55 records · Page 3Linked to original sources

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↗

Mouse models of emotional postpartum disorders.

In women the first days postpartum are often associated with the onset of major emotional upheaval. Both the cause and the significance of this emotional vulnerability are largely unexplored. A complex interrelationship of emotional and endocrine factors suggests the possibility of a borderline endocrine/neurotransmitter condition, which can be precipitated to some extent by environmental factors. Increased risks are not limited only to nutritional deficiency, infections, and metabolic disorders, since several surveys have shown that women frequently take psychotherapeutic agents at some time during their pregnancy. In this frame, behavioural analysis in animal models appears to be a valuable and sensitive tool for detecting subtle alterations in CNS function, which can be produced by early exposure to psychotropic agents devoid of major teratogenic potential, be they therapeutic drugs or drugs of abuse. The approach has considerable relevance in view of the fact that all or most of the affected subjects can remain within the limits of normal variation until the time of a particular life event, such as for example, the early postpartum period analyzed here, with its enormous physiological and behavioural changes. The emphasis in behavioural teratology should be on naturally occurring species-typical behaviours that form an integral part of the normal behavioural repertoire. So, the series of studies reviewed here was performed with mice to assess the consequences of acute or prenatal benzodiazepine exposure, with focus on the early postpartum period. The role of the genotype on the sensitivity to an antiepileptic (phenobarbital) drug exposure has also been investigated. The aim was of providing significant information on the nature of changes in the female emotional repertoire, which characterizes this specific life event.

Animals↗

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↗

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↗

Sexual segregation in infancy and bi-directional benzodiazepine effects on hot-plate response and neophobia in adult mice.

In the present experiment, the hypothesis that rearing animals in conditions of sexual segregation in infancy (ISS) would affect their adult behavioral reactivity to drug or environmental challenges was tested. Outbred Swiss CD-1 mouse litters were reduced at birth to six pups according to three conditions: MM (all males), MF (sex-balanced composition), and FF (all females). At weaning (day 21), all mice were rehoused in unisexual groups. At adulthood (day 70), animals were challenged either with BDZ agonist chlordiazepoxide (CDP at 2.5- or 5.0-mg/kg dose) or BDZ receptor partial inverse agonist Ro 15-3505 (RO at 3-, 10-, or 30-mg/kg dose) and assessed in sequence for pain reactivity in a hot-plate apparatus (set at 55 +/- 1 degrees C), for locomotor activity in a Varimex apparatus, and finally for neophobia level by measuring the latency to first approach a novel object. As concerns the hot-plate test, lick latency was significantly shortened in MF females receiving CDP (5.0 mg/kg), while RO was either ineffective in MF females or induced a prominent dose-dependent analgesia in FF females. Activity was decreased by CDP (2.5 mg/kg) and enhanced by RO (3.0 mg/kg). For latency to approach a novel object, males as a whole exhibited shorter times than females. Mixed-sex animals of both sexes were less fearful, being also more explorative than their corresponding unisexually reared groups. In particular, MF males receiving either a 5.0-mg/kg CDP dose or a 3.0-mg/kg RO dose explored the object more often than MM males.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

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↗

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↗

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↗

Morphine effects on mouse locomotor/exploratory activity: test dependency, test reliability, uni- and multi-variate analyses.

Drug and toxicant effects on locomotor/exploratory activity can be quite variable depending on the test and the schedule of exposure. In neurobehavioral toxicology and teratology, these interactions can affect the inferences based on the use of selected drugs as probes to assess which regulatory mechanisms are affected by one or the other treatment. The present experiments were aimed at comparing morphine effects in CD-1 mice under three conditions, namely, Varimex apparatus (VAR), toggle floor box (TOGGLE), videotape recording (VIDEO) in a home cage environment. Morphine HCI (0, 10, 33, or 100 mg/kg) was given IP 20 min before the start of a 30-min test session. The same procedure was repeated 24 h later. Results of VAR and TOGGLE tests were: dose 10 was largely ineffective; dose 33 induced depression in VAR and hyperactivity in TOGGLE; dose 100 enhanced activity in TOGGLE. There were no differences between session 1 and 2. VIDEO: Univariate analysis results showed that morphine produced a dose-dependent depression of Rearing and Grooming, and an enhancement of Crossing, again without changes due to repeated exposure. Results of Principal Component Analysis supported a response competition model of the changes observed in the mouse behavioral profile. The videorecording (VIDEO) procedure is the one providing the most accurate picture of changes in locomotor/exploratory activity and drug effects thereon, also allowing a more comprehensive statistical analysis of the relationships between various types of response changes.

Animals↗

Interacting effects of oxazepam in late pregnancy and fostering procedure on mouse maternal behavior.

The present study was designed to assess the proactive effects of late pregnancy benzodiazepine (BDZ) treatment on maternal behavior in the postpartum period, using cross-fostering procedures to control for the role of changes produced prenatally in the offspring. Outbred CD-1 mouse dams were treated with either oxazepam (OX, 15 mg/kg PO twice/day on pregnancy days 12-16) or vehicle (VEH). After parturition, entire litters were exchanged either within treatments (in-fostered groups, IF) or between treatments (cross-fostered groups, CF), while additional litters were left undisturbed (un-fostered groups, UF). The behavior of lactating dams was observed in their home cages at 4, 8, and 12 days postpartum. Maternal responses, particularly nursing, were reduced in the OX-UF and OX-CF conditions and either normal or enhanced in the OX-IF condition. Correspondingly, locomotor/exploratory activity was markedly enhanced in the former conditions and close to the control level in the latter condition. In sum, the fostering variable appeared to determine whether pups raised by dams treated previously with BDZ receive either insufficient or exaggerated maternal care. This points to the need for a better understanding of mother/pup interactions in studies aimed at characterizing drug and toxicant effects on offspring development.

Animals↗

Genetic differences in maternal behaviour patterns in mice administered phenobarbital during pregnancy.

In a study designed to examine the role of the genotype on sensitivity to drug-induced behavioural changes, pregnant C57BL/6J and CBA mice were administered 60 mg/kg phenobarbital (PHB) intraperitoneally during days 10-16 of gestation. Following a balanced intrastrain fostering procedure, the behaviour of lactating dams was observed in their home cage at 2, 3, 5, 7 and 14 days postpartum. As the pups became older, maternal behaviour declined in control groups, whereas PHB dams of the CBA strain persisted in nursing their pups. C57 dams were generally affected in an opposite way by PHB exposure. For example, treated dams spent significantly less time in licking behaviour. Nest quality score was especially elevated in PHB dams of the CBA strain, while in C57 dams, nest-building was inhibited and nest quality unaffected by the previous PHB exposure. These results indicate that specific items of maternal behaviour can be differently affected by PHB exposure, and that the responses are affected by the genotype. To summarise, pups raised by treated dams may receive either exaggerated or insufficient maternal attention, as a result of changes in neurotransmitter systems and behavioural regulation following phenobarbital exposure. These results point to the need for a better understanding of mother/pup interactions in studies aimed at characterizing drug and toxicant effects on postnatal development.

Animals↗

Ontogeny of muscimol effects on locomotor activity, habituation, and pain reactivity in mice.

Three hundred and twenty mouse pups of both sexes of the CD-1 outbred strain received IP muscimol and were subsequently assessed for locomotor activity (single Varimex 30-min session) and for hot-plate responding. Muscimol doses were 0.05, 0.1, or 0.2 mg/kg at 8 and 14 days, and 0.1, 0.5, or 1.0 mg/kg at 21, 28, and 35 days. Activity data showed a shift from an immature pattern at 8 and 14 days to an adult-like pattern from day 21 onwards (high initial activity followed by a marked within-session decrement). Muscimol was ineffective on day 8, and depressed activity from day 14 onwards. At 28 days, however, the higher-dose male group showed a non-monotonic trend of activity; that is an initial depression followed by a marked rebound hyperactivity. With regard to hot-plate exposure, muscimol was ineffective at 8 days, while it produced maximal analgesic effects on day 14, followed by a progressive decrease in drug sensitivity. Around day 70, mice of the former 0.1 mg/kg and saline groups were re-tested for locomotor activity and pain reactivity without additional drug treatment. Activity was generally higher in males than in females, and two groups habituated significantly less than the others (females tested in the muscimol state at 8 days and males tested in the saline state at 35 days). Moreover, prior testing at the earliest ages and prior muscimol exposure had additive attenuating effects on pain reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Litter gender composition affects maternal behavior of the primiparous mouse dam (Mus musculus).

Thirty-nine litters of the outbred Swiss CD-1 mouse strain were reduced at birth to 6 pups, according to three conditions: MM (all males), MF (3 males and 3 females), or FF (all females). The maternal behavior of their respective dams (frequency and duration of nursing, licking, nest-building, and other activities such as eating, drinking, sniffing, grooming, and undirected locomotor activity) were scored during a single 10-min session on Days 2, 3, 5, 7, 10, 14, and 18. Dams rearing MM litters showed higher scores of maternal care on Days 2 and 18 in the case of nursing, on Days 2, 7, and 10 in the case of nest-building, and on Day 18 in the case of licking. These results confirm previous rat data, which indicated that male and female pups are exposed early in infancy to a different pattern of maternal behavior. Concomitant measurements of pup development (body-weight gain and achievement of a number of physiological and neurobehavioral landmarks) indicated that these effects of litter gender composition are not mediated by gross changes in the maturational trends of the pups.

Animals↗

Ontogenetic and pharmacological dissociation of various components of locomotor activity and habituation in the rat.

Sprague-Dawley-derived male rats were used to investigate locomotor activity and habituation in an open field as a joint function of developmental age (2-6 weeks), pattern of test exposure (single 30-min test vs three 5-min tests at 24-hr intervals), and treatment conditions (i.p. saline, d-amphetamine sulfate 1 mg/kg, or scopolamine hydrocloride 0.5 mg/kg). No-drug animals showed low activity levels in both tests at the end of the second week, intermediate response rates at the end of the third week, and a typical adult-like pattern at later ages (high initial activity followed by marked within-session or between-session habituation). Amphetamine effects varied considerably depending jointly on age and type of test. At the end of the second week, the drug hyperactivity was much more marked in successive brief tests than in the single extended test. One week later, the response increase was rather uniform in both tests. At the end of the fourth week, the sensitivity profile was reversed, consisting of a large drug effect in the extended test but not in successive brief tests. Scopolamine was still without effects at this age, while a typical hyperactivity was produced by the drug in 6-week-old animals. These data show that, at least in the rat strain used, the functional maturation of muscarinic regulatory systems is not a necessary condition either for the appearance of an adult-like response pattern, or for the occurrence of the age- and test-related changes of the amphetamine profile.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Morphine effects on activity and pain reactivity of developing mice with or without late prenatal oxazepam exposure.

Locomotor activity in a Varimex apparatus, hot-plate responding, and morphine effects (1 and 10 mg/kg IP) were assessed in 14-, 21-, 28-, and 70-day old mice. The development of hot-plate responding consisted mainly of a progressive increase of latencies and a parallel reduction of sensitivity to morphine. Morphine depressed activity at 14 days at the lower dose, had no effect at 21 days, and produced an adult-like hyperactivity at 28 days (10 mg/kg). Prenatal oxazepam (15 mg/kg, given per os twice daily on days 12-16 of pregnancy) did not influence hot-plate responding and morphine analgesia at any of the test ages. By contrast, the data on activity, besides replicating the response reduction at 14 days observed previously in an open-field test (Alleva et al. 1985), showed a delayed appearance of morphine hyperactivity in oxazepam mice.

Aging↗

Short-term and delayed behavioral effects of pre- and post-weaning morphine in mice.

Ninety mouse pups of the CD-1 outbred strain were used to assess activity (Varimex Activity Meter, Columbus Instr., OH) and analgesia (hot plate) after morphine hydrochloride given IP either on days 14-16 (preweanlings) or on days 21-23 (postweanlings). In preweanlings morphine depressed activity already at the lowest dose tested (0.5 mg/kg), and higher doses (1, 5, and 10 mg/kg) did not produce a significantly larger effect. Activity of postweanlings was not depressed until a very high dose (20 mg/kg). By contrast, morphine produced clear analgesic effects at all doses in both preweanlings (day 14) and postweanlings (day 21). Around day 70, activity and hot-plate tests in the no-drug state showed no differences due to prior treatment, except for the fact that hot-plate latencies of mice previously injected with saline as preweanlings were higher than those of all other groups. Twenty-four hr later the tests were repeated after morphine injection (10 mg/kg), and showed a significantly greater depression of activity in mice previously exposed as preweanlings. On the other hand, all groups previously exposed to morphine at either the pre- or the post-weanling stage showed tolerance to the analgesic effect of the drug. These developmental profiles confirm that opioid systems contribute to the modulation of activity by mechanisms which are at least in part separate from those mediating analgesia.

Age Factors↗

Postnatal social environment affects morphine analgesia in male mice.

Seventy-eight male mice of the Swiss CD-1 strain were maintained from birth to weaning either in litters containing only male pups (MM), or in litters containing both male and female pups (MF). Body weight gain and neurobehavioral development were assessed, and no differences between MM and MF males were found. On postnatal day 40 one male from each litter (N = 13 per group) was injected either with vehicle (saline solution, 8%) or with morphine (5 or 10 mg/kg). Fifteen min after the injection, forepaw licking latencies were measured in a hot plate test (55 +/- 1 degree C). MF males showed longer latencies than MM males, and this difference was statistically significant after both morphine doses. These results indicate that the function of systems mediating response to painful stimulation and opiate analgesia can be affected by variations in early social conditions.

Aging↗