Effect of selection for behavior on the cranial traits of the American mink (Mustela vison)

Cranial sizes of American mink selected for tame and aggressive behavior (towards humans) and control mink, which were not selected for behavior, were compared. Absolute sizes of the skull were demonstrated to change depending on the direction of selection. Sexual dimorphism was reduced in mink selected for aggressive behavior, because the cranial sizes of females increased and those of males decreased. Cranial traits were analyzed by the method of principal components. The groups studied differed from one another with respect to the first four components. Although the vector of selection determined the differences between the groups, some morphological changes were similar in the groups selected for tame and aggressive behavior.     

Genetical aspects of hormonal modification of the stress reactivity. II. Modification in early ontogenesis of the stress reactivity of adult gray rats selected for behavior toward man

Inherited and modificational changes of the stress reactivity in two outbreed stocks of wild Norway rats trapped in nature and selected for behaviour were studied. During 18 generations the rats of one stock were selected for the lack of defensive behaviour in the glove test (tame), while in another stock the aggressiveness was maintained by the selection (aggressive). Interstock differences in the brain noradrenaline mechanisms were observed. The emotional stress reactivity of the tame animals was decreased, in comparison with the aggressive ones. Definitive stress reactivity of adult rats was modified by injections of hydrocortisone to their mothers on the 16 and 18 days of gestation. Hormonal treatment changed noradrenaline mechanisms and decreased the reaction to emotional stressor in aggressive rats. The modified level of the stress reactivity of aggressive rats was similar to the definitive level of the tame ones. Hormonal treatment did not modify stress reactivity in tame rats. Thus, the phenotype only emerging in aggressive rats, as a result of hormonal modification, is the inherited norm of the tame animals. However, due to rat selection for the lack of defensive behaviour towards the man, high corticosteroid level in the blood of pregnant females, an external developmental factor, in respect to the fetus, loses regulatory function during the development of the neuroendocrine mechanisms of the stress reaction.     

Maternal condition reduces fear behaviors but not the endocrine response to an emotional threat in virgin female rats

Lactating dams and maternal virgin females are less fearful in behavioral tests compared with non-maternal animals, suggesting that maternal condition per se reduces the negative value of threatening stimuli. In addition, lactating females exhibit a diminished hypothalamic-pituitary-adrenal response to potential environmental threats. Can the maternal condition, independently of the endocrine profile of lactation, promote a reduction in the behavioral as well as in the endocrine response to an emotional stressor? To answer this question, anxiety-related and fear behaviors as well as the levels of corticosterone were evaluated in response to a bright-lit open field-loud noise model in maternal and non-maternal non-ovariectomized virgin females and lactating dams in the presence of the pups. Maternal animals, both lactating and virgin, presented an increased exploration of the bright-lit open field and a significant reduction of fear behaviors, indicated by the decreased flight and immobility responses to the subsequent activation of a loud noise, in comparison to non-maternal virgins. Interestingly, maternal virgin females, as non-maternal rats, showed high corticosterone plasma levels, in contrast to the lower endocrine response exhibited by lactating dams when confronted to this threat. Present results suggest that maternal condition allows females to take risks when caring for their young, a behavioral strategy that is independent of the reduced hypothalamic-pituitary-adrenal axis response characteristic of lactation. This evidence points towards a clear dissociation in the mechanisms regulating behavioral and endocrine responses to emotional stressors during motherhood.     

Phenotypic differences in behavior, physiology and neurochemistry between rats selected for tameness and for defensive aggression towards humans

To better understand the biology of tameness, i.e. tolerance of human presence and handling, we analyzed two lines of wild-derived rats (Rattus norvegicus) artificially selected for tameness and defensive aggression towards humans. In response to a gloved human hand, tame rats tolerated handling, whereas aggressive rats attacked. Cross-fostering showed that these behavioral differences are not caused by postnatal maternal effects. Tame rats were more active and explorative and exhibited fewer anxiety-related behaviors. They also had smaller adrenal glands, larger spleens and lower levels of serum corticosterone. Blood glucose levels were lower in tame rats, whereas the concentrations of nine amino acids were higher. In the brain, tame rats had lower serotonin and higher taurine levels than aggressive rats. Our findings reinforce the notion that tameness is correlated with differences in stress response and will facilitate future efforts to uncover the genetic basis for animal tameness.     

Vocalization toward conspecifics in silver foxes (Vulpes vulpes) selected for tame or aggressive behavior toward humans

We examined the production of different vocalizations in three strains of silver fox (unselected, aggressive, and tame) attending three kinds of behavior (aggressive, affiliative, and neutral) in response to their same-strain conspecifics. This is a follow-up to previous experiments which demonstrated that in the presence of humans, tame foxes produced cackles and pants but never coughed or snorted, whilst aggressive foxes produced coughs and snorts but never cackled or panted. Thus, cackle/pant and cough/snort were indicative of the tame and aggressive fox strains respectively toward humans. Wild-type unselected foxes produced cough and snort toward humans similarly to aggressive foxes. Here, we found that vocal responses to conspecifics were similar in tame, aggressive and unselected fox strains. Both cackle/pant and cough/snort occurred in foxes of all strains. The difference in the use of cackle/pant and cough/snort among these strains toward humans and toward conspecifics suggest that silver foxes do not perceive humans as their conspecifics. We speculate that these vocalizations are produced in response to a triggering internal state, affiliative or aggressive, that is suppressed by default in these fox strains toward humans as a result of their strict selection for tame or aggressive behavior, whilst still remaining flexible toward conspecifics.     

The effects of prolonged selection for behavior on the stress response and activity of the reproductive system of male grey mice (Rattus norvegicus)

Two Norway rat (Rattus norvegicus) populations contrasting in behavior have been raised at the Institute of Cytology and Genetics, Novosibirsk, Russia with long-term selection for the absence or enhancement of an aggressive response towards humans. They are designated as tame and aggressive, respectively. In this work we investigated the effects of the selection on behavior, stress responsiveness, and function of testes in males of the 78th generation. It is shown that the difference between the strains in their response to humans remains the same as in previous generations. However, the differences in stress response and rate of maturation contradict earlier data. For the first time, we note a higher glucocorticoid-mediated response to restriction stress and retarded sexual maturation in tame rats compared to aggressive ones, according to morphometric indices of gonads and testosterone levels. It is conceivable that the change in selection effects is determined by the disjunction of the directions of selection for behavior and the modification of the stress response. This study is the first to characterize males recently (six or seven generations of propagation in captivity) caught in the wild with regard to the indices under consideration and used as a control group. Wild rats have the highest stress response and rate of sexual maturation as compared to those selected.     

Effect of repeated stress on the function of pituitary-adrenal and immune systems in gray rats selected for behavior

Reaction of pituitary-adrenal axis to a 10-day immobilisation stress and a humoral immune response to subsequent injection of sheep red blood cells were investigated in gray rats selected for enhancement of decrease of aggressive behavior towards humans. It was show that pituitary-adrenal axis reaction of aggressive animals to repeated stress did not change during the experiment, while a decrease of stress-induced corticosterone level was observed already on day 5 of stress. Repeated stress led to enhancement of humoral immune response in aggressive rats, whereas it did not bring about any change in tame animals. based on the obtained data, it could be supposed that breeding of gray rats for domesticated behavior led a faster adaptation to repeated stress and the absence of stimulating influence on humoral immune response in tame rats.     

Effects of maternal methyl-supplement diet on hippocampal glucocorticoid receptor mRNA expression in rats selected for behavior

In the present work, we study glucocorticoid receptor (GR) gene expression in gray rats selected for aggressive and domestic behavior, as well as in offspring of mothers with methyl-supplemented diet during pregnancy. Tame selection is associated with increased GR mRNA expression as compared with aggressive rats, whereas maternal methyl-supplemented diet inhibits GR activity in tame rats. GR gene promoter methylation is an important way of altering GR expression.     

Some features of learning in swimming Morris test in rats selected for behavior towards human

Some features of learning in Morris water test were studied in gray rats after a long-term selection for elimination (tame strain) and enhancement (aggressive strain) of aggressiveness towards human. The content of plasma corticosteroids was estimated at different stages of learning. It was shown that tame rats were better in performance of a special Morris task than aggressive ones. The time of search for invisible platform was increased in aggressive rats owing to the fact that they spent more time near the pool walls. Also, time of rearing at the platform was higher in tame rats compared to aggressive animals. In the retention test, rats of both strains spent significantly more time in the target quadrant than they did in other quadrants. Rats of both strains did not differ in time of search for invisible platform when it was replaced to the opposite quadrant. After the first day of learning, the corticosteroid plasma level was lower in tame rats than aggressive animals. During the following days of training, the content of the hormone increased in tame rats and did not differ from aggressive rats. It is supposed that, in tame rats, low emotionality and stress response facilitated learning in Morris water test.     

Brain CRF-binding protein modulates aspects of maternal behavior under stressful conditions and supports a hypo-anxious state in lactating rats

Reduced corticotropin-releasing factor (CRF) receptor activation in the postpartum period is essential for adequate maternal behavior. One of the factors contributing to this hypo-activity might be the CRF-binding protein (CRF-BP), which likely reduces the availability of free extracellular CRF/urocortin 1. Here, we investigated behavioral effects of acute CRF-BP inhibition using 5 μg of CRF_(6-33) administered either centrally or locally within different parts of the bed nucleus of the stria terminalis (BNST) in lactating rats. Additionally, we assessed CRF-BP expression in the BNST comparing virgin and lactating rats.Central CRF-BP inhibition increased maternal aggression during maternal defense but did not affect maternal care or anxiety-related behavior. CRF-BP inhibition in the medial-posterior BNST had no effect on maternal care under non-stress conditions but impaired the reinstatement of maternal care following stressor exposure. Furthermore, maternal aggression, particularly threat behavior, and anxiety-related behavior were elevated by CRF-BP inhibition in the medial-posterior BNST. In the anterior–dorsal BNST, CRF-BP inhibition increased only non-maternal behaviors following stress. Finally, CRF-BP expression was higher in the anterior compared to the posterior BNST but was not different between virgin and lactating rats in either region.Our study demonstrates a key role of the CRF-BP, particularly within the BNST, in modulating CRF's impact on maternal behavior. The CRF-BP is important for the reinstatement of maternal care after stress, for modulating threat behavior during an aggressive encounter and for maintaining a hypo-anxious state during lactation. Thus, the CRF-BP likely contributes to the postpartum-associated down-regulation of the CRF system in a brain region-dependent manner.     

Hormonal factors influence the onset of maternal aggression in laboratory rats

This experiment addressed the hypothesis that aggressiveness toward conspecifics is stimulated by hormonal factors known to mediate the onset of maternal care. Subjects included both pregnant and virgin females. Sixteen-day pregnant rats were hysterectomized (H), hysterectomized-ovariectomized and injected with estrogen (HO-EB), or subjected to sham procedures. Nonpregnant females were HO-EB or sham operated. The females were sensitized by continuous exposure to pups and were judged to have initiated maternal care when all pups were retrieved and grouped, Aggressiveness was observed during 5-min intruder tests using unfamiliar males, administered (a) 10 min prior to the introduction of test pups, (b) following the first 3 hr of pup exposure, and (c) after females had initiated maternal care. The results revealed that treatments known to reduce sensitization latencies also increased aggressiveness even prior to exposure to pups. Aggressiveness was displayed before sensitization only in groups having elevated estrogen levels. After initiating maternal behavior, pregnant and pregnancy-terminated females increased further in aggressiveness whereas nonpregnant females did not. Pregnancy-terminated, HO-Oil females became aggressive (only) after initiating maternal behavior, indicating that factors other than estrogen also influence the onset of maternal aggression.     

Effect of Behavior Selection on the Morphofunctional State of Pineal Gland in Norway Rats

Functional state of pineal gland in female Norway rats selected for tame and aggressive behavior was analyzed using stereometric technique. Activity of epiphysis in tame rats (the study was performed in November, during diestrus stage) was evaluated higher than in aggressive rats. Data obtained are discussed in comparison with results of selection for behavior of silver foxes.     

Targeted resequencing of a genomic region influencing tameness and aggression reveals multiple signals of positive selection

The identification of the causative genetic variants in quantitative trait loci (QTL) influencing phenotypic traits is challenging, especially in crosses between outbred strains. We have previously identified several QTL influencing tameness and aggression in a cross between two lines of wild-derived, outbred rats (Rattus norvegicus) selected for their behavior towards humans. Here, we use targeted sequence capture and massively parallel sequencing of all genes in the strongest QTL in the founder animals of the cross. We identify many novel sequence variants, several of which are potentially functionally relevant. The QTL contains several regions where either the tame or the aggressive founders contain no sequence variation, and two regions where alternative haplotypes are fixed between the founders. A re-analysis of the QTL signal showed that the causative site is likely to be fixed among the tame founder animals, but that several causative alleles may segregate among the aggressive founder animals. Using a formal test for the detection of positive selection, we find 10 putative positively selected regions, some of which are close to genes known to influence behavior. Together, these results show that the QTL is probably not caused by a single selected site, but may instead represent the joint effects of several sites that were targets of polygenic selection.     

The pleiotropic effect of selection for behavior on coat color in grey rats (Rattus norvegicus)

The effects of selection for a type of behavior relative to humans (tame and aggressive) on the intensity of coat color in agouti rats with the AAHH genotype were studied. Animals that were not under selection for behavior (wild animals) were used as the control. Morphometric analysis of the hair parameters that influence the intensity of coat color demonstrated that, on the one hand, polymorphism in the main coat color exists in the population of wild agouti rats, that is, both light and dark agouti animals exist. On the other hand, it was demonstrated that selection for a type of behavior in rats is accompanied by selection of animals that differ in the intensity of the main genetically identical coat color. Dark-colored animals are more prevelent among the aggressive animals, while light-colored animals prevail among tame animals. The association of the effects of selection for behavior with the modification of coat color is probably caused by the presence of common neurohormonal mechanisms for the regulation of these processes.     

哺乳期棕色田鼠对配偶的识别记忆

观察了分娩后哺乳雌性棕色田鼠（Microtus mandarinus）与配偶分离7d、14d、21d后对配偶与陌生雄鼠的行为反应。结果发现,在频次和持续时间上,与配偶分离7d、14d、21d的雌鼠对配偶的攻击行为显著低于陌生雄鼠（P〈0．05）;对配偶的嗅闻及友善行为显著高于陌生雄鼠（P〈0．05）。处于哺乳前、中、后期不同阶段的雌鼠对陌生雄鼠攻击水平没有显著性差异（P〉0．05）。这些结果说明,在整个哺乳期,雌鼠能够识别配偶,对配偶的记忆不因分离时间的增加而减弱,而且对陌生鼠的攻击水平不会因哺乳阶段的变化而变化,维持高水平的攻击可能与其较强的母性行为有关。     

Comparison of the "nursing" and other parental behaviors of nulliparous and lactating female rats

Virgin female rats display maternal behaviors after continuous exposure to pups (sensitization) that are in some respects similar to those of postpartum females. We herein provide a detailed comparison of the "nursing" and other parental behaviors of maternally sensitized virgin females and postpartum lactating dams. Ovariectomized and intact virgin females were exposed to pups until displaying maternal behavior. On the females' fourth day of maternal responsiveness, the pups were removed for 3 h and then returned, and subject-litter interactions were observed for 45 min. Behavior of maternal virgins was compared with that of lactating dams observed on day 4 postpartum interacting with either suckling pups or pups unable to suckle due to perioral anesthesia. Ovariectomy had no effect on behavior of virgins. Retrieval and licking of pups were deficient in virgins compared with lactating dams. Suckled dams showed prolonged kyphosis (upright crouched nursing), whereas nonsuckled dams displayed little kyphosis but rather were often in a hunched position over pups. Some aspects of quiescent "nursing" behaviors of virgins were surprisingly similar to those of suckled dams, including the latency to and duration of quiescence. Nonsuckling pup stimulation elicited more kyphosis in virgins than in lactating dams, which was still much less than in suckled dams. Virgins also "nursed" pups in hunched and prone postures. Differences between sensitized and postpartum females in their maternal behaviors likely reflect differences in motivation as well as sensory inputs they receive from pups. In particular, sensory regulation of "nursing" behaviors is influenced by reproductive state because nonsuckling pups elicit different postural responses in sensitized and lactating mothers.     

Maternal methyl supplements affect the phenotypic variation of the <Emphasis Type="Italic">agouti</Emphasis> gene in the offspring of rats with different behavioral types

The effects of selection of agouti rats (with genotype AAHH) on the tame and aggressive behavior and dietary methyl given to females from the eighth day of pregnancy to the fifth day after the birth of the offspring on the intensity of the agouti coat color in the offspring have been studied. The morphometric parameters of hair determining the darkness of the agouti color (the total length of guard hairs, the lengths of their eumelanin end and pheomelanin band, the ratio between the lengths of the eumelanin and pheomelanin portions of the hair, the total length of the awn hairs, and the relative length of their widened “lanceolate” upper end) have been compared. It has been found that selection of agouti rats for aggressive behavior is accompanied by darkening of the coat color compared to tame rats due to an increase in the ratio of the length of the black eumelanin end of the guard hairs to the length of the yellow pheomelanin band. Methyl-containing additives to the diet of females affect the intensity of the agouti coat color in the offsprings with both types of behavior, but to different extents. Aggressive offspring is more sensitive to the mother’s methyl-containing diet: the percentage of animals that are darker than control rats is higher among aggressive animals than among tame ones due to a greater increase in the ratio between dark and light portions of hairs. The possible mechanisms of differences in the phenotypic modifications of coat color in control and experimental agouti rats with different types of behavior are discussed.     

Behavioral and physiological characteristics of nonagouti mutation in gray rats during selection for aggressiveness

The goal of this work was to find out to which degree the black coat color mutation nonagouti that appears in wild Norway rat in the course of breeding for the maintenance and enhancement of aggressiveness towards a human affects selected and other behavioral traits as well as stress reactivity and brain neurochemistry. Nonagouti rats displayed increased emotionality in the open-field and forced-swimming tests as compared to agouti animals, whereas there were no differences in anxiety estimated in the elevated plus-maze. Neither were there any differences in glucocorticoid reactions to a combined stressful procedure such as forced swimming. The dopamine content in the frontal cortex and striatum and noradrenaline content in the frontal cortex were increased in black rats as compared to gray rats. The result suggest that the nonagouti mutation in gray aggressive rats enhances the effects of selection for aggressiveness on some behavioral traits and brain catecholamine level.     

Further evidence for the role of nitric oxide in maternal aggression: effects of L-NAME on maternal aggression towards female intruders in Wistar rats

It has been shown that nitric oxide (NO) increases aggression in male mice, whereas it decreases aggression in lactating female mice and prairie voles. It is also known that aggression can be exhibited at different levels in rodent species, strain or subtypes. The aims of this study were to investigate the proportion of aggressiveness in Wistar rats, the effect of intraperitoneally administered nonspecific nitric oxide synthase (NOS) inhibitor L-NAME (NG-nitro L-arginine methyl ester) on maternal aggression towards female intruders, and whether these effects are due to NO production or not. Rats were given saline intraperitoneally on the postpartum Day 2 and aggression levels were recorded. The same rats were given 60 mg/kg L-NAME or D-NAME (NG-nitro D-arginine methyl ester) on the postpartum Day 3 and their effects on aggression levels were compared to saline. While L-NAME administration did not cause any differences in the total number of aggressive behavior, aggression duration and aggression intensity, it reduced the proportion of animals showing aggressive behavior. In addition, the latency of the first aggression was significantly increased by L-NAME. In the D-NAME group, however, no significant change was found. Our results have shown that L-NAME reduces maternal aggression towards female intruders in Wistar rats through inhibition of NO production. These results suggest that the role of NO in offensive and defensive maternal aggression shares neural mechanisms.     

The role of brain noradrenaline in regulating the endocrine function of the gonads in male brown rats selected for behavior

In two groups of gray rats--nonaggressive ones, selected by the lack of aggression towards investigator, and aggressive animals--studies have been made on the relationship between noradrenaline system of the brain and the activity of pituitary-testicular system. In tame rats, less evident dependence of the gonadal activity on activating effect of noradrenaline was noted. After injection of norepinephrine, dopamine, and serotonin in the same brain region. *****were less significant in tame rats as compared to those in aggressive ones. The disturbed relationship between noradrenaline system of the brain and hypothalamo-pituitary-testicular complex is presumably one of the causes of associate changes in the reproductive system during selection for the domestic type of behaviour.