| The central nervous system of organisms is not yet mature at early postnatal development. Any noxious stimuli during this period might affect the development of brain structure, thus altering the function of brain. Early life stress is very important risk factor that can cause some neuropsychiatric diseases, such as attention deficit hyperactivity disorder, schizophrenia, autism and etc. The closest relation with organisms after birth is their mothers. Maternal relationship plays an important role in brain development at early postnatal days. When the babies and their mothers were separated for several weeks or longer, abnormal behavioral phenotype could be observed after they grew up. Although the pathogenesis of these abnormal behaviors is not known, some studies show that there are dysfunctions of monominergic neurotransmitters found in thes patients. Animal experiments show that mother rats are not only necessary for the neonatal offspring survival, but also for the development of the nervous system. Therefore, the present study used early separation of neonatal rats as experimental animal models, in order to observe the effect of the early maternal separation of neonatal offspring on the behaviors and its mechanism.Objective: To observe the effect of the early maternal separation of neonatal offspring on the behaviors and its mechanism.Methods: The neonatal rats 7 days after birth were randomly divided into normal control group, maternal deprivation group and materal separation group. Open-field behaviors were documented of rats at 49 days after birth and then immunohistochemistry were done to reveal the altered dopaminergic and serotonergic neurons in related brain regions. Results: 1 Open field test: The number of vertical movement in maternal deprivation group and in materal separation group were significantly more than that in normal control group (P<0.01). Grooming latency in maternal deprivation group and in materal separation group was shorter than in normal control group (P<0.01).Immunohistochemistry:1) TH immunohistochemistry results: Optical density analysis showed that optical density value of TH immunoreative intensity in the substantia nigra and caudate nucleus in maternal deprivation group was significantly higher than that in normal control group. 19%, 11% (P<0.05), 42% and 19% (P <0.01) increases in substantial nigra, dorsomedial part of caudate-putamen, ventral tegmental area and ventomedial part of caudate-putamen were found compared to corresponding control group. 21%, 2% (P<0.05), 49% and 8% (P <0.01) increases in substantia nigra, dorsomedial part of caudate-putamen, ventral tegmental area and ventromedial part of caudate-putamen were found in materal separation group compared to corresponding control group.2) DAT immunohistochemistry results: Optical density value of DAT immunoreative intensity in substantia nigra, ventral tegmental area and caudate-putamen in maternal deprivation group was significantly higher than that in normal control group. 23%, 21% , 19% (P<0.01) and 11% (P<0.05) increases were respectively found in substantia nigra, ventral tegmental area, ventromedial part of caudate putamen and dorsomedial part of caudate-putamen compared to corresponding control. 22%, 15%, 8% (P<0.01) and 8% (P<0.05) increases were observed in substantia nigra, ventral tegmental area, ventromedial part of caudate-putamen and dorsomedial part of caudate-putamen in materal separation group were found compared to corresponding control group.3) TPH immunohistochemistry results: Optical density value of TPH immunoreative intensity in dorsal part of dorsal raphe nucleus respectively rises 46% and 42% (P<0.01) in maternal deprivation group and materal separation group compared to normal control group. 47% increases in ventrolateral part of dorsal raphe nucleus were found in materal separation group compared to control group (P<0.01).4) 5-HT immunohistochemical results: Optical density value of 5-HT immunoreative intensity in ventrolateral part of dorsal raphe nucleus increases 54% and 26% (P<0.01) in maternal deprivation group and materal separation group respectively compared to normal control group. 46% and 28% increases in ventrolateral part of dorsal raphe nucleus were found in materal separation group and materal separation group compared to control group (P<0.01).5) SERT immunohistochemistry results: There is no significant difference of optical density value of sert immunoreative intensity in ventral part of dorsal raphe nucleus between maternal deprivation group and normal control group. 45% rises in ventrolateral part of dorsal raphe nucleus compared to that in normal control group (P<0.01).Conclusion: Early separation of neonatal rats altered open-field behaviors and increased TH and DAT expression in substantial nigra and caudate-putamen, as well as TPH,5-HT and SERT expression in dorsal raphe nucleus, suggesting that early separation of neonatal rats might pertain to pathogenesis of some neuropsychiatric diseases, such as attention deficit hyperactivity disorder, anxiety, autism and schizophrenia.
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