Moderate prenatal alcohol exposure and quantification of social behavior in adult rats.

Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE(1), and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring.

Reciprocal affiliation among adolescent rats during a mild group stressor predicts mammary tumors and lifespan.

OBJECTIVE: Although the detrimental physical health effects of social isolation have been known for three decades, the answers to how and why social relationships generally improve health remain elusive. Social relationships are not always beneficial, and we examined a structural dimension that may bring about their salubrious effects: affiliative reciprocity during a stressor. METHODS: In a lifespan study, female rats lived with their sisters and were tested for temperament, affiliative reciprocity during an everyday stressor at puberty, corticosterone response to a stressor, mammary tumor development and diagnosis, and death. RESULTS: Rats that affiliated more reciprocally during a mild group stressor survived longer (p = .0005), having exhibited a lower corticosterone peak in response to an acute novel stressor in late adulthood (p = .0015), and longer time to the development of spontaneous mammary tumors (p = .02). These effects could not be explained solely by the number of affiliative interactions or individual temperament. Indeed, affiliative reciprocity and neophobia were independent and predicted mortality additively (p = .0002). CONCLUSIONS: Affiliative reciprocity during a stressor, a structural quality of social interactions, protected females from early mammary tumor development (the primary pathology in Sprague-Dawley rats) and early all-cause mortality. Conversely, lack of reciprocity (whether disproportionately seeking or receiving attempted affiliation) was as potent a risk factor as neophobia. Thus a social role increased risk additively with individual temperament. Our data indicate that affiliative reciprocity functions as a buffer for everyday stressors and are likely mediated by attenuated reactivity of the hypothalamic-pituitary-adrenal axis.

Elevated testosterone and reduced 5-HIAA concentrations are associated with wounding and hantavirus infection in male Norway rats.

Among rodents that carry hantaviruses, males are more likely to engage in aggression and to be infected than females. One mode of hantavirus transmission is via the passage of virus in saliva during wounding. The extent to which hantaviruses cause physiological changes in their rodent host that increase aggression and, therefore, virus transmission has not been fully documented. To assess whether steroid hormones and neurotransmitters contribute to the correlation between aggression and Seoul virus infection, Norway rats were trapped in Baltimore, Maryland and wounding, infection status, steroid hormones, and concentrations of neurotransmitters, including norepinephrine (NE), dopamine (DA), 3,4-dihydroxyphenol acetic acid (DOPAC), serotonin (5-HT), and 5-hydroxyindole-3-acetic acid (5-HIAA) in select brain regions were examined. Older males and males with high-grade wounds were more likely to have anti-Seoul virus IgG and viral RNA in organs than either juveniles or adult males with less severe wounds. Wounded males had higher circulating testosterone, lower hypothalamic 5-HIAA, and lower NE in the amygdala than males with no wounds. Infected males had higher concentrations of testosterone, corticosterone, NE in the hypothalamus, and DOPAC in the amygdala than uninfected males, regardless of wounding status. In the present study, wounded males that were infected with Seoul virus had elevated testosterone and reduced 5-HIAA concentrations, suggesting that these neuroendocrine mechanisms may contribute to aggression and the likelihood of transmission of hantavirus in natural populations of male Norway rats.

Microsatellite analysis reveals that female mice are indiscriminate when choosing infected or dominant males in an arena setting.

Considering that both infection and dominance status can be conveyed through urinary odours and both are thought to affect mate choice, the present study assessed the role of infection and male dominance status on female mate choice in arena enclosures. Three male CD-1 mice were simultaneously introduced into each of 4 spatially complex arenas (3.0 x 0.6 x 0.4 m high) for 24 h prior to introduction of 5 females into each arena. During the first mating sequence (i.e. Mating 1), all 3 males were uninfected. Prior to Mating 2, the dominant male in each arena was infected with 200 L3 of Heligmosomoides polygyrus (Nematoda). Prior to Mating 3, the dominant male was drug-treated to remove the parasite. Dominance was assessed by the absence of rump or tail wounds (Freeland, 1981). Females were removed from the arena when visibly pregnant, and returned for subsequent mating 2 weeks following parturition. Paternity was determined by microsatellite analysis of each pup. Multi-male mating (i.e. mating with 2 or all 3 males) was a common strategy among females as littermates were sired by 2 or all 3 males in 64 % of the litters. Contrary to expectation, the dominant male did not sire the majority of offspring in any of the mating sequences, and infection and subsequent drug treatment of the dominant male did not have a significant impact on female mate choice. In addition to methodological differences in paternity determination (i.e. DNA analysis versus behavioural observations and/or phenotypic traits), these findings may be further explained by the spatial complexity of the experimental arenas.

Local variation in helminth burdens of bank voles (Clethrionomys glareolus) from ecologically similar sites: temporal stability and relationships with hormone concentrations and social behaviour.

Populations of bank voles (Clethrionomys glareolus) in a fragmented forest habitat in north-east Poland showed local differences in helminth infection intensity, morphometric measures and organ weights that were consistent with differences at the same locations two years previously. Although overall intensities of infection were lower than previously, and there were some differences in the relative intensities of individual helminth species, site differences remained significant and were consistent across replicated subsites. In keeping with site differences in helminth infection and adrenal gland weight and asymmetry, voles at site 1 (high intensity infection) had higher circulating concentrations of corticosterone than those at site 2 (low intensity infection). Since males were sampled outside the breeding season, and thus non-scrotal, testosterone levels were low and did not differ between sites. As previously, voles at site 1 also showed greater hind foot asymmetry. Dyadic interactions between males from the same and different sites in the laboratory showed that males from site 1 were significantly less aggressive, especially when confronted with intruder males from site 2. There was no relationship between aggressiveness and intensity of infection overall or at site 1, but a significant negative relationship emerged at site 2. Aggression thus appeared to be downregulated at the higher intensity site independently of individual levels of infection. Terminal corticosterone concentrations were greater at site 1 and lower among residents that initiated more aggression. While corticosterone concentrations rose over the period of testing, they did not correlate with the amount of aggression initiated or received.

Local variation in helminth burdens of Egyptian spiny mice (Acomys cahirinus dimidiatus) from ecologically similar sites: relationships with hormone concentrations and social behaviour.

Populations of Egyptian spiny mice (Acomys cahirinus dimidiatus) in a fragmented montane wadi system in the Sinai showed significant differences in the abundance of gut helminths. Differences in parasite load between populations were positively associated with measures of androgen activity but showed no significant relationship with glucocorticoid activity. Social discrimination tests with adult males from different wadis showed that those from sites with greater helminth abundance were less likely to investigate odours from other males and were less aggressive when subsequently interacting with the odour donors. Subjects showed markedly more investigation towards the odours of males from distant wadis compared with those from their own or immediately neighbouring wadi, but were less aggressive when confronted with odour donors from distant wadis. Despite this, there was a positive relationship between the amount of investigation towards distant male odour and subsequent aggression towards the male. While aggressiveness was positively associated with measures of androgen and glucocorticoid activity, no significant relationship emerged with individual helminth infection. Thus aggressiveness appeared to relate to overall local population levels of infection rather than individual challenge.

Parasite-altered host behavior in the face of a predator: manipulation or not?

Parasitologists have generally accepted the idea that parasite-induced alterations in host behavior increase the chance for parasite survival and transmission or ensure the completion of its life cycle. The aim of the present study was to investigate modifications in the behavior of Taenia crassiceps-infected BALB/c mice in the face of a predator. The experiments showed modifications in the response of infected mice in comparison with uninfected controls on exposure to a predator final host. However, different studies lead us to suggest that the observed modifications are likely to be a secondary effect of the impact of the parasite on host physiology and immunity that favors its development and proliferation.

Mouse model of hyperkinesis implicates SNAP-25 in behavioral regulation.

Although hyperkinesis is expressed in several neurological disorders, the biological basis of this phenotype is unknown. The mouse mutant coloboma (Cml+) exhibits profound spontaneous locomotor hyperactivity resulting from a deletion mutation. This deletion encompasses several genes including Snap, which encodes SNAP-25, a nerve terminal protein involved in neurotransmitter release. Administration of amphetamine, a drug that acts presynaptically, markedly reduced the locomotor activity in coloboma mice but increased the activity of control mice implicating presynaptic function in the behavioral abnormality. In contrast, the psychostimulant methylphenidate increased locomotor activity in both coloboma and control mice. When a transgene encoding SNAP-25 was bred into the coloboma strain to complement the Snap deletion, the hyperactivity expressed by these mice was rescued, returning these corrected mice to normal levels of locomotor activity. These results demonstrate that the hyperactivity exhibited by these mice is the result of abnormalities in presynaptic function specifically attributable to deficits in SNAP-25 expression.

Failure to find behavioural differences between lean and obese Zucker rats exposed to novel environments.

Past studies have evidenced a key role for hypercorticism in the obesity syndrome of the Zucker (fa/fa) rat. Here, the hypothesis that obesity-related hypercorticism is associated with increased anxiety/emotionality was tested in the elevated plus-maze, the black/white box, and the open field. In the elevated plus-maze, none of the parameters examined (open arm entries, time in open arms, total number of entries) differed between lean (Fa/?) and obese (fa/fa) rats. In addition, neither the behaviours measured in the black/white box (latency to enter the black compartment, number of transitions, time spent in the white compartment, locomotion, rearing) nor those measured in the open field (locomotion, rearing, grooming, defecation) were affected by obesity. This study suggests that obesity-related hypercorticism in fa/fa rats is not associated with indices of emotionality and anxiety, at least those analysed by means of the tests used here.

Effect of Toxoplasma gondii upon neophobic behaviour in wild brown rats, Rattus norvegicus.

The effect of Toxoplasma gondii on neophobic behaviour (the avoidance of novel stimuli) was assessed in four groups of wild rats with naturally occurring Toxoplasma infection. Two groups were placed in individual cages and tested in a series of experiments which examined the effect of Toxoplasma on the rat's reaction to 3 food-related novel stimuli (odour, food-container, food). A trappability study was performed on the other two groups to test whether Toxoplasma had an effect on probability of capture. The results show that low neophobia was significantly associated with positive Toxoplasma titres in 3 out of 4 groups. We suggest that differences between infected and uninfected wild rats arise from pathological changes caused by Toxoplasma cysts in the brains of infected rats. Such behavioural changes may be selectively advantageous for the parasite as they may render Toxoplasma-infected rats more susceptible to predation by domestic cats (the definitive host of Toxoplasma) and, as a side-effect, more susceptible to trapping and poisoning during post control programmes.

Social isolation modifies the response of mice to experimental Mengo virus infection.

To investigate the effects of social isolation on host resistance male mice were housed either individually (IH) or in groups of four or five (GH). All animals were infected with MengoM,L virus. Incubation time (INCUB), duration of illness (ILL), death rate (DR), histopathological changes, and serum corticosterone levels (CORT) were recorded. First, the effect of IH starting 4 days prior to infection was studied in 5 different inbred strains. Next, the effect of different IH length was examined, and the role of T-cells was investigated by comparing euthymic (+/+) and athymic (nu/nu) NMRI mice. Finally, the effects of the infection on CORT in IH and GH mice were compared in C57BL/6 mice. The major findings were: 1. IH significantly increased ILL in all but the DBA/2 strain, whereas DR was not affected except in C57BL/6. 2. Longer IH (starting 35 [DBA/2] or 10 [NMRI] days prior to virus inoculation) significantly shortened INCUB and prolonged ILL, but IH starting on the day of virus inoculation [DBA/2] significantly prolonged INCUB and shortened ILL. 3. NMRI nude mice exhibited an unaltered DR accompanied by a tremendously prolonged INCUB. 4. Investigations in C57BL/6 mice revealed a significant rise of CORT after infection. This increase was higher in IH compared to GH mice. It is suggested that IH attenuates T-cell mediated inflammatory processes and/or increases macrophage activation, which in turn results in a prolonged course of the disease.

Social behaviour, stress and susceptibility to infection in house mice (Mus musculus): effects of duration of grouping and aggressive behaviour prior to infection on susceptibility to Babesia microti.

Unrelated and initially unfamiliar male CFLP mice, maintained for different periods in groups of 6, differed in both their rate of clearance of Babesia microti and the time taken to reach peak parasitaemia in relation to their aggressive behaviour within groups prior to infection. Males maintained in groups for shorter periods and showing more aggression within their group were slower to clear infection and males showing more marked external evidence of aggressive interaction reached a peak of parasitaemia sooner. Serum IgG and corticosterone analyses were consistent with increased aggression causing stress-induced immunodepression but relationships with aggression and social status were not simple. Males showing more aggression tended to enter their groups with higher levels of corticosterone and, to a lesser extent, reduced levels of IgG compared with other mice. The results thus suggest that increased susceptibility to disease may be a cost to males aggressively maintaining high social status.

The psychoneuroendocrinology of diabetes mellitus in rodents.

The metabolic-endocrine state of diabetes mellitus affects the brain and behavior of diabetic animals. Feeding, paradoxical sleep, analgesia, submissive behavior, and avoidance behavior, are generally increased in diabetic compared with nondiabetic rodents. In contrast, sexual behavior, aggressive behavior and sensitivity to the behavioral effects of amphetamine are decreased in diabetic rodents. This review examines behavioral changes in diabetes mellitus within the context of known disease-linked alterations in hypothalamo-pituitary relationships and brain monoamine metabolism.

Behavioral testing of progenies of Tx (hypothyroid) and growth hormone-treated Tx rats: an animal model for mental retardation.

Virgin Sprague-Dawley Holtzman rats were rendered Tx (hypothyroid) by radiothyroidectomy and maintained on 1.0 microgram T4 (thyroxine) per 100 g BW until pregnant. One-half of these Tx animals were administered 0.5 IU of growth hormone (GH) during the last 10-11 days of gestation as GH secretion is especially deficient in Tx rats. Untreated, food restricted to the level consumed by the Tx-only rats, GH-treated euthyroid, and T4-treated until pregnant animals served as controls. The animals were allowed to go through parturition and each litter was reduced to no more than 6 pups by removing pups for tissue weights and protein analyses at 1 and 5 days of age. The pups were weaned at 22 days of age and 2 animals per litter were utilized for behavioral testing between 40 and 60 days of age. At the end of the behavioral testing period the 60-day-old offspring were sacrificed to obtain tissue weights and protein concentrations. The behavioral tests were based on the ability of the animals to learn a Lashley's type 3 enclosed alley maze and their spontaneous activity was measured in stabilimeter cages. The animals were fasted overnight on alternate days and then given a food reward upon traversing the maze. This allowed for 10 separate trials in both the Lashley maze and the stabilimeters over the 20-day period from 40 to 60 days of age. Our previous studies have shown the fetuses and progenies of Tx-only mothers to have multiple metabolic defects including reduced rates of protein synthesis and tissue protein concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)