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

Abstract

It is known that neonatal handling may cause long-term changes in neurobiological and behavioral phenotypes. The neonatal handling of rats selected for enhanced aggressiveness towards humans (“aggressive” rats of generation 44) significantly mitigates aggression and stress responsiveness. However, the levels of corticosterone in stress in intact aggressive rats of later (70s) generations are lower than in generation 44, which differ little from the corresponding value in “tame” rats, selected in the opposite direction, for the absence of the aggressiveness towards humans. The goal of the present study is to find out whether the decrease in the stress response in aggressive rats at the current stage of selection is accompanied by a decrease in the influence of handling on aggressiveness. Experiments have been conducted with the Norway rat populations of the 75th generation of selection for aggressive and tame behavior, respectively. It has been found that the neonatal handling of aggressive animals causes a significant decrease in aggressiveness, albeit, considerably smaller than in generation 44. In both aggressive and tame rats, the blood corticosterone level under stress returns to the basal level for a longer time than in the corresponding control groups. Neonatal handling decreases the amount of mRNA for the glucocorticoid receptor (GR) in the hippocampus of aggressive rats but does not significantly affect the amount of mRNA for the corticotropin-releasing hormone (CRH) in the hypothalamus. However, in the control groups the level of CRH mRNA recorded in aggressive rats is higher than in tame ones. On the contrary, no differences in the GR mRNA are found between the strains, in contrast to earlier generations. It has been shown that the neonatal handling of pups is beneficial for maternal behavior in tame rats. Thus, the results obtained in generation 75 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 glucocorticoid-mediated 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.