Proton magnetic resonance spectroscopy of neurometabo­lites in the hippocampi of aggressive and tame male rats

Proportions of major neurometabolites with regard to their total amount in the dorsal region of the hippocampus were studied in adult male rats of populations selected for long for increase and absence of aggressivefearful response to humans and in unselected vivarium- kept rats by 1H magnetic resonance spectrometry. Tame and unselected males showed no significant differences in the proportions of any neurometabolites studied. Differences in the proportions of some neurometabolites were found in aggressive vs. tame and in aggressive vs. unselected animals. Tame animals showed higher pro­portions of GABA, N-acetylaspartate (NAA), and choline derivatives and a lower proportion of phosphoryl­ethanolamine than aggressive ones. It is likely that the elevated content of GABA, one of the main inhibitory neurotransmitters in the brain, lowers excita­tion intensity in tame pups in comparison to aggressive ones. In comparison to unselected animals, aggressive rats demonstrated higher proportions of glutamine, aspartate, phosphorylethanolamine, and lactate and lower proportions of NAA and creatinine+ phosphocreatinine. Aspartate is one of the main excitement transmitter, and its elevated proportion in the brain of aggressive rats may favor more intense excitation than in unselected rats. In contrast, the elevated proportion of glutamine in aggressive rats vs. tame rats may be indicative of (1) a metabolic disturbance in the glutamate–glutamine cycle, which links neural and glial cells, and (2) decrease in the activity of glutaminase, the enzyme converting glutamine to glutamate (GABA precursor). The reduced NAA proportion together with the elevated proportion of glutamine in aggressive rats point to impaired energy metabolism in comparison to unselected animals. The differences in neurometabolite patterns between hippocampi of male rats of the unselec­ted and aggressive populations suggest the existence of different neurobiological mechanisms governing aggression manifestation

Effects of neonatal handling on behavior and stress-response in rats selected for reaction towards humans

It is known that neonatal handling may cause longterm changes in neurobiological and behavioral phenotypes. Neonatal handling of rats selected for enhanced aggressiveness towards humans (“aggressive” rats of generation 44) significantly mitigated aggression and stress responsiveness. However, levels of corticosterone in stress in intact aggressive rats of later generations (70s) were lower than in generation 44, which differed little from the corresponding value in “tame” rats, selected in the opposite direction, for the absence of aggressiveness towards humans. The study was conducted with Norway rat populations of the 75th generation of selection for aggressive and tame behavior, respectively. The goal was to find out whether the decrease in stress response in aggressive rats at the current stage of selection was accompanied by a decrease in the influence of handling on aggressiveness. It was found that neonatal handling of aggressive animals caused a significant decrease in aggressiveness, although considerably smaller than in generation 44. In both aggressive and tame rats, the blood corticosterone level at stress was getting back to the basal level for a longer time than in the corresponding control groups. Neonatal handling decreased the amount of mRNA for the glucocorticoid receptor (GR) in the hippocampus of aggressive rats but did not affect significantly the amount of mRNA for the corticotropin-releasing hormone (CRH) in the hypothalamus. However, higher contents of CRH mRNA were recorded in aggressive rats than in tame ones in the control groups. However, no differences in glucocorticoid receptor mRNA  were found between the strains in contrast to earlier generations. It was shown that neonatal handling was beneficial for maternal behavior in tame rats. Thus, the results obtained in the 75th generation of selection indicate that the effect of handling on aggressiveness weakens with decreasing stress responsiveness in aggressive rats. This is likely to be related to the changing amount of GR in the hippocampus and stronger glucocorticoidmediated feedback at the current stage of selection. The minor prolongation of the stress response appears to be related to the stressing component of neonatal handling rather than to changes in maternal care

REDERIVATION BY EMBRYO TRANSFER IN STRAINS OF LABORATORY MICE AND RATS

Rederivation allows laboratory animal populations to be purged from specified pathogens and thus turns these animals to the SPF (specified pathogens free) status. Results of the rederivation of two unique rat strains selected at the Institute of Cytology and Genetics and one mouse strain are presented. The two rat strains are: tame Norway rats and rats with Inherited Stress Induced Arterial Hypertension (ISIAH strain). The ICR mouse strain has been named as abbreviation of the Institute of Cancer Research wherefrom these mice were distributed to laboratories all over the world. The SPF status of the rats after rederivation was confirmed by the method of indicator animals (sentinel animals). The optimized model of rederivation offered here involves a combination of such embryotechnological methods as freezing/cryopreservation of embryos, their washing through the number of fresh volumes of sterile media, growing in vitro for 48 hours, and subsequent transfer into either one or both uterine horns of recipient females. Application of this model to rederivation of ICR mice yielded 39 pups born in an SPF vivarium. It should be noticed that the effectiveness of the procedure met international standards, and characteristic features of phenotype were retained in all the three strains after rederivation

EFFECTS OF SOCIAL EXPERIENCE IN ADOLESCENCE: BEHAVIOR AND STRESS-RESPONSE IN NORWAY RATS SELECTED FOR ATTITUDE TO HUMANS

The influence of social experience in adolescence (early separation from the mother and change partner in cage and keeping in twos in cage) on anxiety behavior, social behavior and stress-response investigated in tame, aggressive and unselected male rats. Aggressive behavior in experimental unselected and aggressive rats reduced in comparison with control animals. The testosterone level reduced after restriction stress in experimental unselected rats and corticosterone level reduced in experimental aggressive rats in comparison with control animals.Работа выполнена при поддержке Российского фонда фундаментальных исследований (грант № 12-04-00494-а)

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. Heredity (2011) 107, 205-214; doi: 10.1038/hdy.2011.4;published online 9 February 201