PubMed Health⌕ Search

Biomedical subjects

E Alleva

Publications and source records attributed to E Alleva.

At least 127 records · Page 7Linked to original sources

Pretreatment of young mice with nerve growth factor enhances scopolamine-induced hyperactivity.

Twenty-one-day-old mice show a characteristic enhancement of locomotor activity upon injection of the cholinergic (muscarinic) blocking drug scopolamine. Intracerebral (third ventricle) injection of nerve growth factor (NGF) 24 h prior to scopolamine injection significantly enhances the drug-induced hyperactivity without modifying baseline activity. Such potentiation of the scopolamine effect was not obtained in 10-week-old mice treated and tested similarly.

Age Factors↗

Postnatal maturation of brain cholinergic systems in the precocial murid Acomys cahirinus: comparison with the altricial rat.

The spiny mouse (Acomys cahirinus) is the only precocial murid species. It has some neuroanatomical peculiarities such as a relatively thin cerebral cortex and a large hippocampus. The levels of choline acetyltransferase, membrane-bound acetylcholinesterase and muscarinic receptor sites (measured as [3H]quinuclidynil benzilate binding) were assessed in the whole brain on days 1, 7, 14, 21, 28 and 80 (adult), and compared with those of Wistar rats of the corresponding ages. At birth choline acetyltransferase was significantly higher in spiny mice than in rats but the adult levels were similar, with an overall increase of about 5.2- and 14-fold for the former and the latter species, respectively. Membrane-bound acetylcholinesterase level and maximal density of muscarinic receptor sites in spiny mice were considerably higher at birth, in contrast adult levels were significantly lower than in rats with a respective overall increase of about 1.5- and over 4.5-fold. The high degree of maturity attained at birth by spiny mice partially depends on the long gestation period. However, if we consider postconception age, the maturation of choline acetyltransferase appears to be delayed at birth in the spiny mice, probably in relation to the lack of external stimulation during intrauterine life. In the cerebral cortex, hippocampus and striatum of adult spiny mice, when compared with the rats, there were similar levels of choline acetyltransferase but lower levels of membrane-bound acetylcholinesterase and, in the cerebral cortex, lower density of muscarinic receptor sites.

Acetylcholinesterase↗

Odor-aversion learning and retention span in neonatal mouse pups.

One hundred and sixty-four litters of Swiss CD-1 random-bred mice were used to assess learning and retention capacities during the first postnatal week. In Experiment 1, whole 7-day litters were exposed for 65 min to commercial extracts of either mint or lemon sprinkled over wood shavings. Five minutes after the beginning of the exposure, half of the litters were injected ip with the illness-inducing agent lithium chloride (LiCl; 0.20 M, 2% of body weight); the other half was treated with saline solution (8% NaCl). On Postnatal Day 10, the animals were singly introduced in a warmed arena for a 180-s preference test, and the time spent in the mint- and lemon-scented areas of the apparatus was recorded. When compared with saline-injected pups, mice that experienced lemon-LiCl pairings showed a significant aversion for the lemon-scented area, while the mint aversion in the mint-LiCl group just missed statistical significance. Three additional control groups (unhandled on Day 7, or only LiCl- or saline-injected) did not show significant preferences for either the mint or the lemon odor. In Experiment 2, litters of 3, 5, or 7 days were similarly exposed to lemon-scented shavings for either 5 or 20 min, injected with LiCl or saline, and then exposed for an additional 60 min to the shavings. On Postnatal Day 10, tests like those of Experiment 1 showed a significant odor-aversion in animals conditioned on Day 7, but not in those conditioned on Day 3 or 5. In Experiment 3, 3- and 5-day old pups were exposed to lemon odor-LiCl or -NaCl pairings, and tested for aversion after 3 or 7 days (CS duration 5 min before injection and either 30 or 60 min after injection). Only when the conditioning-testing interval was limited to 3 days did LiCl-injected groups show a significant aversion, which did not depend on duration of CS exposure.

Animals↗

Aggressive behavior induces release of nerve growth factor from mouse salivary gland into the bloodstream.

Intraspecific fighting induced by 6-8 weeks of social isolation results in massive release of nerve growth factor (NGF) into the bloodstream of adult male mice. The amount of circulating NGF is highly correlated with the number of fighting episodes. Biological, radioimmunological, immunohistochemical, and ultrastructural studies show that NGF is discharged from the salivary gland into the blood within minutes after fighting and reaches the highest level 3-4 hr later. Adrenergic innervation of the salivary gland or adrenalectomy does not abolish the NGF release. Corticotropic hormones do not induce NGF increase in the blood. Daily administrations of highly purified NGF (3 micrograms per g of body weight) result in a considerable increase in the volume of adrenal glands. These findings are unequivocable evidence for a physiological role of the mouse salivary glands as a major source of blood NGF.

Adrenalectomy↗

Prenatal benzodiazepine effects in mice: postnatal behavioral development, response to drug challenges, and adult discrimination learning.

Oxazepam treatment of primiparous mouse dams on days 12-16 of pregnancy (15 mg/kg p.o. twice daily) produced a transient retardation of postnatal body growth and neurobehavioral development, a reduction of the hyperactivity response to amphetamine in open-field tests on postnatal days 14-16, and a selective impairment of adult active avoidance in four go-no go discrimination tasks. Equally important for understanding the nature of the prenatal benzodiazepine syndrome were several negative results, namely, the absence of changes in homing performance on postnatal day 10, an intact hyperactivity response to scopolamine on postnatal days 21-23, a lack of effects on adult activity, and a normal passive avoidance performance in the go-no go tasks. A modification in monoaminergic regulatory functions may account for the overall profile of prenatal drug effects. Based on the results of this experiment, of a preliminary multidose study (0-50 mg/kg), and of an additional cross-fostering experiment, several methodological issues are addressed. These include the choice of appropriate treatment schedules and of testing procedures adequate for each developmental stage, and the control for various confounding variables such as litter effects, postnatal maternal influences, and developmental history.

Amphetamine↗

Short-, medium-, and long-term effects of prenatal oxazepam on neurobehavioural development of mice.

A benzodiazepine (oxazepam) was given to nulliparous mice on days 12-16 of pregnancy, and the development and young adult behaviour of the offspring were studied. Experiment 1, using 5, 15, and 50 mg/kg doses given PO twice daily, showed a dose-dependent retardation of postnatal development of several responses such as righting, bar holding, limb placing, and auditory startle. These changes were maximal in the first 2 postnatal weeks and then were markedly attenuated, or disappeared, being apparently related to a temporary retardation of body growth. A reduction of locomotor activity at 60 days was found only in the 50 mg/kg group. The effects of the 15 mg/kg dose on postnatal body growth and neurobehavioural development were replicated in Experiments 2 and 3. Moreover, in these experiments prenatal oxazepam reduced open field activity at 14-16 days and attenuated the hyperactivity induced by dl-amphetamine sulphate (2 mg/kg IP). On the other hand activity, habituation, and response to a scopolamine challenge (2 mg/kg IP) at 21-23 days were not significantly different from those of appropriate controls. Experiment 3, using a cross-fostering procedure, showed that postnatal maternal effects were not responsible for the changes so far mentioned. Experiment 2 also investigated the acquisition of several go-no go avoidance discriminations in a shuttle-box, using either light (L) or buzzer noise (N) as the "go" signal, a compound "no go" signal (NL in the L-"go" groups and LN in the N-"go" groups), and either an extinction or a passive avoidance contingency during the "no go" signal (4 weeks of training, starting at 60 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗

Development of mouse activity, stimulus reactivity, habituation, and response to amphetamine and scopolamine.

Twenty-four litters of non-inbred Swiss-derived mice were used to study the development of locomotion and tendency to approach a novel object in an open field, as well as the effects of dl-amphetamine sulfate and scopolamine hydrochloride (1 or 2 mg/kg IP). Brief (7 min) tests repeated for three consecutive days were preferred in order to obtain information on between-session habituation. Animals tested on days 14-16 showed low levels of activity without changes in successive sessions. In contrast, an adult-like pattern with a high initial activity and marked between-session decrements prevailed on days 21-23 and 28-30. Dl-amphetamine elevated activity only on days 14-16, while scopolamine produced hyperactivity and impaired habituation only on days 21-23 and 28-30. Latency to approach a novel object by untreated animals showed a substantial reduction between the end of the second week and subsequent developmental stages. This went hand in hand with an appearance of latency increases after dl-amphetamine treatments, while an opposite trend in the scopolamine data failed to reach statistical significance. Activity tests in a photocell apparatus at 61-72 days (without prior treatment) showed a reduction of locomotion relative to the level measured in animals from other litters raised in parallel and not subjected to early testing. Overall, the present data and those of the literature indicate that some developmental phenomena in small rodents are relatively insensitive to a variety of organismic, environmental, and test factors, while others (e.g., inverted U-shaped activity trends and successive modifications of the amphetamine profile) depend on complex interactions between several variables.

Age Factors↗

Amphetamine, conditioned stimulus, and nondebilitating preshock effects on activity and avoidance: further evidence for interactions between associative and nonassociative changes.

A literature survey and preliminary experiments with rats on the consequences of shock preexposure on subsequent activity and escape or avoidance showed the need for further work on the interactions between nondebilitating preshock and various test and treatment factors. The two main experiments used 16 preexposure conditions, namely, presence or absence of unavoidable punishment (36 shocks of 2.5 mA and 5 sec subdivided in three daily sessions), a light CS, a central partition in the shuttle-box, and dl-amphetamine sulfate (1 mg/kg ip 15 min before each session). In both experiments the four factors studied exerted more than additive effects on activity in preexposure sessions, leading to a very high frequency of crossing in the CS-shock-no-partition-drug condition. Upon retesting for activity (Experiment 1) suppression of locomotion by prior shock was less marked in animals preexposed to CS-US pairings in the absence of partition, while proactive amphetamine effects consisted mainly of a progressive increase of activity over successive retest sessions in the groups not preshocked. Upon retesting for light-cued, two-way avoidance acquisition (Experiment 2) the groups preexposed to US only were mostly retarded, while those preexposed to paired CS and US were mostly facilitated. Other changes, including drug pretreatment consequences, were negligible or unsystematic, but in general the data showed that the effects of various preexposure conditions on activity could not account for those on avoidance. Overall, it appears that the interactions between nondebilitating preshock and other test and treatment factors can be further exploited to clarify the respective roles of various associative and nonassociative mechanisms in modulation of activity and adaptive responding in aversive situations.

Amphetamine↗

Effects of isolation on activity, reactivity, excitability and aggressive behavior in two inbred strains of mice.

In order to investigate mechanisms of isolation-induced aggressive behaviour, inbred mice of the C57BL/6 and DBA/2 strains were individually housed over a period of 8 weeks. In the DBA/2 strain only, isolation was followed by a clear increase in activity (Animex), reactivity (reactions upon tactile body stimulation), excitability (duration of EEG desynchronization elicited by tactile stimulation of the thorax area under urethane anesthesia) and intermale aggression (biting and fighting responses). The use of inbred strains of mice proved to be a useful tool for the examination of the relationship between various parameters. It is concluded that there are no clear correlations between activity, reactivity and aggressive behavior and that the resulting aggressive responses in the DBA/2 strain are likely due to the increase of excitability.

Aggression↗

Ontogeny of behavioral development, arousal and stereotypes in two strains of mice.

A number of reflexes and amphetamine-induced locomotor and stereotyped behavior were assesses in 8, 16, 32, 90 and 360 day old C57BL/6J and SEC/1ReJ inbred mice. The data indicate that C57 mice are more precocious for a number of neuronal and behavioral mechanisms while SEC mice are less mature at birth. In addition, there are appreciable fluctuations of these behavioral patterns throughout life. A rise in arousal levels was evident in both strains between 8 and 16 days and between 32 and 90 days of age. Three-hundred-sixty days old mice presented a general decrease in the levels of arousal. These findings are discussed in terms of neuronal and behavioral plasticity and in relation to the ontogeny of the different catecholaminergic systems which modulate excitory and inhibitory different behavioral patterns at different ages.

Aging↗

Nerve growth factor influences neurobehavioral development of newborn mice.

Thirty-six male pups of the CD-1 outbred strain received from postnatal day 2 to day 10 a daily subcutaneous injection of either highly purified murine Nerve Growth Factor (NGF; 5 mg/kg), cytochrome c (5 mg/kg), or saline solution. NGF-treated pups showed a slight, but significant, reduction in body weight gain and a concomitant acceleration in the appearance of early signs of neurobehavioral maturation such as righting reflex, cliff aversion, and response to tactile stimulation of the perioral area. Other responses, including the ultrasonic vocalization pattern on day 7, were unaffected or affected to a lesser extent.

Animals↗

Problems of test choice and data analysis in behavioral teratology: the case of prenatal benzodiazepines.

Higher-tier tests for the assessment of early treatment effects should be aimed at providing specific information on the behavior processes affected, rather than simply at extending the descriptive data base. The contrast between positive and negative results can be useful to point out possible mechanisms of action. For example, late prenatal oxazepam exposure of mice produced a reduction of the amphetamine hyperactivity at the end of the second postnatal week, but did not significantly affect the response to scopolamine at the end of the third week. An impairment of active locomotor avoidance was observed at the young adult stage, which contrasted with the absence or scarcity of changes in passive avoidance and extinction responding in the same go-no go tests. These changes in response-activating mechanisms appear to be in agreement with the medium- and long-term effects on CNS monoamine metabolism described in the literature. As concerns statistical analysis, dichotomous or polytomous data obtained, e.g., by the Fox battery are not yet amenable to an adequate processing, due to the shortcomings of the available nonparametric tests. By contrast, mixed-model ANOVAs can cope with complex data obtained, e.g., in activity and learning tests. However, the available checks on various assumptions (normality, homogeneity of variance, sphericity) are not valid when nested factors, block factors and repeated measures coexist. Finally, the more usual cross-fostering procedures provide adequate information on some aspects (e.g., separation of main effects of prenatal treatments from postnatal maternal effects) but not on others.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prenatal oxazepam enhances mouse maternal aggression in the offspring, without modifying acute chlordiazepoxide effects.

In the rat, behavioral changes during lactation are in several ways similar to those produced by benzodiazepines (BDZ). Moreover, an increased activity at the GABA/BDZ receptor complex has been found in both conditions. We tested the hypothesis that early manipulation of this neurochemical system by prenatal BDZ exposure should affect typical responses of lactating dams, such as maternal aggression. Outbred CD-1 mice were treated with either oxazepam (15 mg/kg PO twice/day on days 12-16 of fetal life) or vehicle and fostered at birth to untreated dams. Female offspring were subsequently mated at the young-adult stage and used to assess maternal aggressive responses towards a male intruder. In a first 5-min test on postpartum day 6, the prenatal oxazepam animals showed a reduced Latency to the First Attack, a markedly enhanced frequency of several offensive scores (such as Fighting Episodes, Attacks, and Offensive Upright, On Top, and Kicking Postures), a decrease of Submissive Postures and a reduced duration of time spent lying still (Out of the Nest). The tests were repeated 48 h later after IP treatment by either chlordiazepoxide (10 mg/kg) or saline. The drug significantly enhanced locomotor activity as well as the frequency of Fighting Episodes and of Attacks, while decreasing the number of Submissive Postures and the time spent On Nest. These effects were not significantly modified by prenatal oxazepam exposure. This suggests that long-term and acute effects of benzodiazepines are produced either by changes in different regulatory systems or by different types of changes in the same system.

Aggression↗

Development of GABAergic modulation of mouse locomotor activity and pain sensitivity after prenatal benzodiazepine exposure.

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. Locomotor activity (single 30-min session in a Varimex apparatus), hot-plate responding, and muscimol (GABAa agonist) effects thereon [see normative data in (16)] were assessed on postnatal day 14, 21, or 28. Prenatal oxazepam did not affect the development of hot-plate responding and muscimol analgesia; however, it reduced activity on day 14 (as in previous studies) and modified the profile of muscimol effects at 21 days (time of first appearance of an adult-like pattern of activity) and at 28 days. Specifically, oxazepam mice showed a faster recovery from the initial depression after 1 mg/kg of muscimol at the former age and a lack of rebound hyperactivity at the latter age. These effects might be explained either 1) by an accelerated development of GABAergic regulatory mechanisms, or 2) by the same monoaminergic system changes which can account for other effects of prenatal BDZ exposure (1,3). In any event, the dissociation phenomena found in the present study strengthen the notion that GABAergic influences contribute to the modulation of locomotor activity and of pain reactivity by mechanisms which are at least in part separate from each other (16).

Analysis of Variance↗

Prenatal oxazepam effects on cocaine conditioned place preference in developing mice.

The positively reinforcing and activity enhancing effects of IP cocaine (0, 5, or 25 mg/kg) were assessed at three ages (14-17, 21-24, and 28-31 days) in outbred CD-1 mouse pups treated prenatally by either oxazepam (OX, 15 mg/kg PO twice/day on days 12-16 of pregnancy) or vehicle (VEH). A 4-day unbiased conditioned place preference (CPP) procedure was used with combined visual and tactile cues (white walls and wide-mesh metal floor versus black walls and narrow-mesh floor). A single 25 mg/kg cocaine dose produced CPP in both prenatal groups of 28-31 day-old mice. At the two younger ages, a significant cocaine CPP was found in prenatal OX mice but not in vehicle animals; the latter apparently developed CPP less readily than the offspring of indisturbed dams in a previous experiment. On the other hand, prenatal OX did not produce substantial changes in the developmental profile of cocaine effects on locomotor activity, consisting of a dose-related response enhancement which is much more marked at 22 and 29 days than before weaning.

Aging↗

Neonatal exposure to bFGF exerts NGF-like effects on mouse behavioral development.

Brain cells are naturally exposed to a variety of trophic factors during development. Basic Fibroblast Growth Factor (bFGF), a protein found in the central nervous system (CNS) enhances both survival and proliferation of several CNS cell lines. Neonatal mice of the CD1 outbred strain were injected intracerebroventricularly (ICV) with bovine bFGF on postnatal days 2, 4, and 7. bFGF, dissolved in 25 microliters of saline, was given in the 1, 5, 25, and 1000 ng doses. Physical traits such as body weight gain, body length, and tail length were recorded from postnatal day (PND) 2 to PND 12. Neurobehavioral development was scored according to a modified Fox's Scale. The ultrasonic vocalization pattern (PND 8), homing performance (PND 10), open-field activity and exploration of a novel object (PND 18) were also assessed. Pups receiving 25 and 1000 ng doses of bFGF showed a slight but significant acceleration in the appearance of some early sensorimotor reflexes, such as weak and tactile stimulation, forelimb placing and grasping, and screen climbing, during the first postnatal weeks. The other responses were less affected or not affected at all. Data are compared with similar systemic exposure of neonatal mice to Nerve Growth Factor (NGF).

Animals↗