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.

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.

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.

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.

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.

An updated role for nerve growth factor in neurobehavioural regulation of adult vertebrates.

Increasing attention has been focused on the role(s) of nerve growth factor (NGF) in neurobehavioural regulations of adult vertebrates. This interest springs from the emerging evidence that NGF is a "regulator" of physiological processes belonging to the three main homeostatic systems: the nervous, immune and endocrine systems. In fact, the spectrum of action of the NGF molecule is not restricted to neuronal cell types (central basal forebrain; peripheral sensory and sympathetic neurons) but extends also to nonneuronal cells.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Litter defence and parental investment allocation in house mice.

In house mice, post-partum maternal aggression against a potentially infanticidal male conspecific can be considered a parental investment act. As such, it constitutes a suitable experimental paradigm for testing parental investment allocation. In the present study, 60 nulliparous female albino mice were tested for maternal aggression on day 8 of the lactation period (single 5-min test exposure to a male intruder).

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.

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.

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).

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.

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.

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).

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.

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.

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.