Effects of postnatal handling on adult behavior and brain mRNA expression of serotonin receptor, brain-derived neurotrophic factor and GABA-A receptor subunit.

Development of brain and behavior is influenced by the interaction of genetic and environmental factors. Postnatal handling, a manipulation that briefly separates mouse offspring from their mother during the postnatal period, has been reported to yield beneficial effects on the behavior of adult offspring. However, brain mechanisms underlying the effects on the behavior have not been well understood. Here we first examined effects of postnatal handling on the behavior of adult male BALB/c mice. Offspring were separated for 15 min every day between postnatal day 1 (P1) and P14 and then various behaviors were tested in the adulthood. Postnatal handling reduced anxiety-like behavior in elevated plus maze and improved spatial learning and memory in Morris water maze without effects on depression-like behavior in forced swim test. Next, to elucidate mechanisms underlying the behavioral effects, we evaluated mRNA expression of the serotonin 1A (5-HT1A) receptor, brain-derived neurotrophic factor (BDNF), and GABA-A receptor subunits in the medial prefrontal cortex, amygdala, dorsal and ventral hippocampi, and dorsal raphe nucleus by quantitative RT-PCR, since these genes and brain regions have been shown to be involved in cognition and emotion. Postnatal handling up-regulated mRNA expression of the 5-HT1A receptor in the dorsal raphe nucleus and down-regulated 5-HT1A receptor mRNA expression in the amygdala on P15 and P71. In adulthood, mRNA expression of BDNF was up-regulated in the amygdala and dorsal hippocampus and down-regulated in the dorsal raphe nucleus, whereas that of GABA-A receptor α2 subunit was down-regulated in the amygdala. Taken together, the present study suggests that postnatal handling reduced anxiety-like behavior and improved learning and memory, which were accompanied by changes in mRNA expression of 5-HT1A receptor, BDNF and GABA-A receptor α2 subunit in the amygdala, 5-HT1A receptor in the dorsal raphe nucleus and BDNF in the dorsal hippocampus.