Biomedical subjects

E Alleva

Publications and source records attributed to E Alleva.

At least 109 records · Page 6Linked to original sources

PubMed1991

NGF and cholinergic control of behavior: anticipation and enhancement of scopolamine effects in neonatal mice.

Male mouse pups of the Swiss-CD1 strain received on postnatal days 2 and 4 either an intracerebroventricular (i.c.v.) administration of 30 micrograms murine nerve growth factor (NGF) or cytochrome c. Pups were then tested for suckling behavior on their anesthetized multiparous dam on day 5, following intraperitoneal (i.p.) administration of either the muscarinic cholinergic antagonist scopolamine (2 mg/kg) or saline solution (0.9%). Scopolamine produced a significant increase in latency time to suckle, while reducing the time pups spent attached to the nipple. NGF exposure enhanced scopolamine effects on latency to suckle as well as on time spent attached to the nipple. More striking, NGF pups showed a marked hyperactivity after scopolamine, an effect which normally appears only around weaning time. These results support the hypothesis that NGF plays a crucial role in the functional maturation of central cholinergic mechanisms involved in the control of behavior.

Animals↗

PubMed1991

Maternal regulation of the adrenocortical response in preweanling rats.

In the following studies, we investigated the effects of 24-h maternal deprivation on the infant's hypothalamic-pituitary-adrenal system. Experiment 1 examined the effect of deprivation on the infant's corticosterone (CORT) response to adrenocorticotropin hormone (ACTH) injection. At all ages studied, deprivation resulted in a potentiation of the response. At some ages, deprived nontreated pups had higher CORT levels than nondeprived pups. Experiment 2 examined the ontogeny of the deprivation-induced stress response, and the capacity of the mother to inhibit it. From 8 days of age onwards, deprived animals showed a CORT response to saline injection that was either absent or far smaller in nondeprived pups. Saline-induced CORT secretion was diminished, or prevented, by returning the infant to its dam. Maternal reunion had no effect on ACTH-induced CORT elevations. Finally, Experiment 3 investigated the effects of deprivation over a more extended period of time. In maternally deprived pups, ACTH-induced CORT elevations persisted for at least 2 h following reunion, but by 6 h had returned to baseline. These data suggest that maternal factors are involved in the regulation of the responsiveness of the pup's hypothalamic-pituitary-adrenal system.

Adrenal Cortex↗

PubMed1991

Capsaicin affects aggressive behavior, but not hot plate responding, of adult male mice.

Adult male mice of albino Swiss-derived CD-1 strain were used to assess the effects of capsaicin (a powerful agent that produces a marked depletion of the undecapeptide substance P) on both intraspecific aggressive behavior (induced by 8 weeks of individual housing) and pain sensitivity. Capsaicin was given SC, 48 h before behavioral testing. Aggressive behavior, scored during a 5-min session under red light, was significantly enhanced by capsaicin treatment (50 or 100 microliters of a 7.5 mg/ml solution). In fact, Total Aggressive Episodes, Attacks, and Upright Offensive Posture were significantly higher in the two capsaicin-treated groups, while Latency to the first Attack was decreased, when compared to both vehicle or unhandled controls. A concomitant decrease in Submissive Postures and Flee was also evident in capsaicin mice. Hot plate testing (55 +/- 0.1 degrees C, cutoff time 30 s), carried out on nonisolated mice, did not reveal any difference among the two capsaicin groups (same doses) and vehicle or unhandled controls.

Aggression↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1990

Changes of NGF level in mouse hypothalamus following intermale aggressive behaviour: biological and immunohistochemical evidence.

Nerve growth factor (NGF) immunoreactivity was detected in the hypothalamus of adult male mice. NGF-immunoreactive cell bodies were examined through consecutive brain sections, and it was found that most of the NGF-positive cells were located in the dorsomedial and mediolateral portions of the hypothalamus. Tissue culture bioassays showed that hypothalamic extract elicits neurite outgrowth from both chick sensory ganglia and rat superior cervical ganglia neurons, and that these effects are inhibited by addition of NGF antibodies. Our results also showed that intermale aggressive behaviour induced by 6-8 weeks of social isolation induces an NGF increase in the hypothalamic area, which is not abolished by sialoadenectomy, suggesting that the increased brain NGF is locally synthesized, and does not come from salivary sources. Likewise, the level of NGF in the hypothalamus of adrenalectomized fighting mice increased, although to a much lesser extent, when compared to hypothalamic levels of sham-operated fighting mice. The present results and a recent report showing that aggressive behaviour causes an increase of mRNANGF in hypothalamic areas are discussed in relation to a possible functional role of NGF in these brain structures.

Aggression↗

PubMed1990

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↗

PubMed1990

Social status and nerve growth factor serum levels after agonistic encounters in mice.

Ten repeated daily interactions (20 min each) of the same pairs of isolated male mice produced a clear distinction between attacking (dominant) and defeated (subordinate) animals. The fighting level remained fairly constant over the 10 days. One hr after the end of the 10th session, the increase in serum NGF levels described previously (2) was significantly more marked in subordinate than in dominant mice. The mean level of serum NGF was correlated with the number of fighting episodes, particularly in the case of dominant individuals. Moreover, within-pair differences in NGF values were correlated with differences in locomotor activity between dominants and subordinates; this makes it possible that stimuli other than those produced by fighting per se may be responsible for the increase in circulating NGF. As is well known, the adrenal hypertrophy produced by fighting stress is more marked in subordinate than in dominant mice, while previous work has shown that stress of a nonpsychosocial kind does not elevate serum NGF levels. Therefore, the present data support the hypothesis that NGF release contributes to the modulation of adrenal function in a situation-specific fashion.

Aggression↗

PubMed1990

Nerve growth factor released into the bloodstream following intraspecific fighting induces mast cell degranulation in adult male mice.

Nerve growth factor (NGF) is stored in the salivary glands of adult male mice. Recent evidence has shown that NGF is active on cell lines of the immune system. Following isolation-induced fighting (20 min session) NGF is released into the bloodstream, causing disruption of cytoplasmic membranes and concomitant degranulation of peritoneal mast cells (MCs). Fluorometric determinations showed an increase in histamine levels in the peritoneal fluid of fighting mice. Administration of NGF antibodies or sialoadenectomy prior to the fighting session blocks MC degranulation. These results, together with other observations, suggest that endogenous NGF plays a physiological role in MC activation.

Aggression↗

PubMed1990

On the functional role of polypeptide growth factors in rodent neurobehavioral development.

A number of polypeptide growth factor molecules have been discovered and characterized in the recent years. Most of them appear to play important roles in the ontogeny of both vertebrates and invertebrates, and some growth factors are specifically involved in brain development of altricial mammals such as rats and mice. In particular, Nerve Growth Factor (NGF) seems to be involved in degenerative processes of the aged CNS and to control brain development, particularly cholinergic systems. Data concerning NGF effects on neurobehavioral development of neonatal mice are reported, and compared with the specific alterations caused by neonatal Epidermal Growth Factor (EGF) exposure on a number of physical and behavioral scores. While NGF mainly anticipated behavioral development, EGF exerted both growth-promoting and growth-inhibiting effects.

Aging↗

PubMed1990

Polypeptide growth factors in mammalian development: some issues for neurotoxicology and behavioral teratology.

Protein molecules known as Growth Factors (GFs) appear to play an important regulatory role in a number of CNS functions. In particular Nerve Growth Factor (NGF), the best characterized among about 30 GF molecules, is endowed with specific activities on cholinergic and peptidergic CNS neurons. Indexes of neurobehavioral maturation are accelerated in the mouse by neonatal NGF exposure, while a similar treatment with EGF exerts both growth-promoting and growth-inhibiting effects on somatic and behavioral development. Scopolamine hyperactivity is enhanced around weaning by NGF pretreatment. Data are discussed along with (a) NGF prevention of cholinergic system damage and (b) the molecular mechanism of endogenously-triggered CNS repair processes.

Animals↗

PubMed1989

Epidermal growth factor has both growth-promoting and growth-inhibiting effects on physical and neurobehavioral development of neonatal mice.

The protein molecule epidermal growth factor (EGF) exerts powerful effects on mouse physical development, since repeated subcutaneous administrations of murine EGF (3.5 mg/kg, from postnatal day 2 to postnatal day 10) cause precocious eyelid opening (as early as day 8 instead of day 13 in control littermates receiving 3.5 mg/kg cytochrome c) and precocious eruption of the lower incisors (day 6 instead of day 8). By contrast, the same EGF treatment retards both the rate of body growth and the full appearance of several neurobehavioral signs of maturation, such as righting and grasping responses. Neonatal mice receiving 5 mg/kg murine nerve growth factor (NGF) under the same treatment schedule, although showing a significant retardation in body weight gain, exhibited only limited changes in neurobehavioral maturation. Specifically, the appearance of slow and swift righting, response to strong tactile stimulation, hindlimb and forelimb grasping, pole grasping, and vertical screen and screen climbing were significantly retarded by EGF and slightly advanced by NGF (the only significant NGF effect was an acceleration of swift righting maturation). Polypeptide growth factors seem to play an important role in physical and neurobehavioral development of altricial rodents, orchestrating the relative maturation of different tissutal targets on different developmental stages.

Aging↗

PubMed1989

Differential effects of prenatal exposure to phenobarbital on the behaviour and neurochemistry of CBA and C57BL/6J mice.

Pregnant C57BL/6J and CBA mice were administered 60 mg/kg phenobarbital intraperitoneally from days 10 to 16 of gestation. On day 18 of pregnancy half of the control and drug-treated mice were killed and the embryonic brains removed for cell cultures. The remaining mice were allowed to have their litter. After cross-fostering the mice were used for behavioural studies. Pups born to drug-treated CBA mice had birth-weights similar to controls, but their weights had fallen behind controls by day 18 after birth. They were slower at attaining mature responses in tests for sensory motor development and became progressively more hyperactive (three times more active at day 18) compared to controls. Drug-exposed C57 pups also had birth weights similar to controls. After cross-fostering, 19% of control and 31% of drug-exposed pups died, but the remaining drug-exposed pups showed no deficits in weight gain. In contrast to drug-treated CBA pups, drug-exposed C57 pups were slightly quicker in attaining mature responses in some tests. There was no difference in activity between them and their controls. In neurochemical analyses, uptake of neurotransmitters by cerebral cultures from CBA showed that uptake of GABA was increased by 5%, choline by 95%, dopamine 120%, serotonin 165% and noradrenaline by 160% in cultures from drug exposed embryos compared to controls. In cerebral cultures from C57, GABA uptake was reduced by 18%, choline 33%, dopamine 35% and noradrenaline by 25%. Only serotonin uptake was increased by 182% compared to controls. Differences between C57 and CBA were also apparent in the uptake of neurotransmitters by neuronal cultures from the mesencephalon.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1989

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↗

PubMed1989

Nerve growth factor mRNA and protein increase in hypothalamus in a mouse model of aggression.

The effects of intermale aggressive behavior induced by social isolation on the level of nerve growth factor (NGF) mRNA and protein were investigated in central and peripheral mouse tissues. A large increase in NGF mRNA and protein was observed in hypothalamus, with no changes in cerebral cortex, hippocampus, and cerebellum. No change in NGF mRNA levels was found in heart, spleen, vas deferens, and submaxillary salivary gland. The cellular localization of NGF mRNA in the central nervous system was investigated by in situ hybridization. Numerous nerve cells were specifically labeled in preoptic and ventrolateral nuclei of the hypothalamus, as well as in the cornu ammonis region of the hippocampus and throughout all layers of the cerebral cortex, with the highest concentration in layer III. The present results firmly establish that nerve cells constitute the major source in NGF in the brain. They also open the way to understanding the regulation of NGF biosynthesis in the central nervous system.

Aggression↗

PubMed1987

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↗

PubMed1987

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↗

PubMed1986

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↗