Part 1:　　Background and objective:　　Mood disorders are one of the most common and devastating psychiatric disorders with lifetime prevalence and results in tremendous secondary costs to society. It is well established that environmental challenges during prenatal period adversely influence normal fetal neurodevelopment and long-lasting ultimately effect on the offspring’s physiology and behavior. The physiological and psychological status of pregnant mothers has been indicated to be associated with an increased risk of developing abnormal cognitive, behavioral and psychosocial outcomes in their offspring. Although accumulated evidence was presented, the underlying neurobiological mechanism of behavior deficit related with PNS was not fully elucidated. Emerging evidence has suggested that GABAergic and glutamatergic systems are implicated in the pathophysiological mechanism of prenatal stress. Moreover, glial cell deficits, especially astrocyte are involved in pathophysiology of mood disorder, in terms of its vital role involving glutamate andγ-amino acid butyric acid (GABA) metabolism. Most neuropsychiatric disorders, including mood disorders, may present early onsets during adolescence amd adolescence is a vital phase of development demonstrating high neuroplasticity and sensitivity to the adverse events. The objective of this study is to verify the hypothesis that adolescent prenatal stressed offspring show behavioral and molecular changes that are related to stress-induced mood disorder, including alteration of expression of glial fibrillary associated protein (GFAP), glial-specific excitatory amino-acid transporters (GLT-1 and GLAST), and GABAergic interneuron markers (GAD 65 and GAD 67) in the brain regions associated with mood regulation.　　Materials and methods:　　Pregnant rats were randomly assigned either prenatal stress group or control group. Restraint stress (45 min ×3/day) was performed from embryonic day 14 (E 14) through E 21. Control dams were left undisturbed in her home cages throughout gestation. After weaning, all the male pups were placed in their own cages and left undisturbed until they were adolescent (PND 30-40). Behavioral tests, including sucrose preference test (SPT), open field test (OFT), novelty suppressed feeding test (NSFT), and elevated plus maze (EPM) were starting from PND 30 through PND 37. Dissected bilateral prefrontal cortex, hippocampus, and amygdala were kept under-80℃for further Western Blot analysis.　　Results:　　Behavioral resultant indicated prenatal stress group showed more sucrose solution consumption than control group, even it was trend increasing (P = 0.08). Prenatal stress increased anxiety-like behavior, characterized with decreased number of entries in open arm of elevated plus maze (P = 0.04). No significant difference was found in sucrose preference percentage (P = 0.18) between two groups. Prenatal stressed rats did not show difference of latency to feed (P=0.70) in novelty suppressed feeding test comparing to control group. There were no difference in center entries time (P=0.97) and time spent in center (P=0.91) in the open field test between two groups. Western blot analysis revealed that PNS decreased protein expression of GAD 65/67 in prefrontal cortex (P=0.08 for GAD 65 and P=0.05 for GAD 67 respectively), although such decreasing trend were not found in both hippocampus and amygdala. No significant change were found in protein level of astroglial maker and excitatory glutamate transporter, even though increasing trend of GLAST was found in hippocampus in PNS group (P=0.07).　　Conclusion:　　1. Prenatal stress induced anxiety-like behavior in adolescent rats.　　2. Prenatal stress decreased GABAergic interneuron of prefrontal cortex in adolescent rats.　　3. The findings highlighted the long-lasting and detrimental effects of prenatal adversities.　　In conclusion, our data provide cross-sectional evidence that PNS potentially caused an increased anxiety-like behavior in the adolescent period, which could be mediated by alteration of GABAergic interneuron in prefrontal cortex.　　Part 2:　　Background and objective:　　It is now well-accepted that interaction between genetic and environmental influences across the lifespan likely underlie vulnerability for depression. Moreover, the childhood period is particularly sensitive to environment disturbance that increase depression risk. Early life stress, characterized stress, abuse, neglect, adverse family relations happened in early life, programming of neurobiological systems that are implicated in regulating emotion and stress responses appears to mediate increased stress vulnerability and depression later in life. Potential factors that might explain outcome variability to the effects of early life stress are remain poorly understood. Accumulating evidence suggested that glutamatergic systems implicated pathophysiological procedure of early life stress. Adolescence is a vital phase of development demonstrating high neuroplasticity and sensitivity to early adverse events. Consequently, the present study investigated the effect of early life stress in adolescent rats on brain neurometabolites, serum corticosterone, and depressive-like behavior.　　Materials and methods:　　Pregnant rats were randomly assigned either early life stress group or control group. Maternal deprivation (3 hr/day) was performed from postnatal day 1 through 14. Control group were left undisturbed in her home cages throughout lactation. After weaning, all the male pups were placed in their own cages and left undisturbed until they were adolescent (PND 30-40). Behavioral tests, including sucrose preference test (SPT) and forced swimming test (FST) were starting from PND 30 through PND 38. Serum and bilateral prefrontal cortex were kept under-80℃ for further analysis.　　Results:　　Behavioral resultant indicated early life stress increased anxiety-like behavior, characterized with dramatically decreased sucrose preference percentage (P<0.001) in the sucrose preference test and significantly increased immobility time (P<0.001) in the forced swimming test. In addition, significantly increased serum corticosterone level (P<0.001) was found in early life stress group. We also found reduced glutamate (P=0.004), glutamine (P<0.001), and N-acetyl aspartate (P<0.001) levels in the prefrontal cortex, even though reduced myo-inositol level was observed was not statistically significant (P=0.09). Finally, reduction in glutamate was limited to female adolescents (P<0.05), instead of males.　　Conclusion:　　1. Early life stress induced depressive-like behavior in adolescent rats.　　2. Early life stress increased corticosterone level in adolescent rats.　　3. Early life stress reduced prefrontal glutamate, glutamine, and N-acetyl asparate.　　In conclusion, our data provide evidence that the effect of early life stress on adolescent animals and underscore the long-lasting and detrimental effects of childhood adversities.　　Part 3:　　Background and objective:　　Depression is a common psychiatric condition characterized with affective, cognitive and psychomotor symptoms with high prevalence. Despite great efforts of researches related to depression and antidepressant agents, there are critical limitations among current treatment options. Emerging novel agents, especially Ketamine, that could potentially provide more efficacious and rapid response rates for depression. Present study is designed to determine dose-response of novel antidepressant agents in rodent, including Ketamine, Ro 25-6981, and Scopolamine.　　Materials and methods:　　Male Sprague-Dawley rats were used in our study. Concentrations for the drugs were as following: Ketamine with 3mg/kg, 30mg/kg, and 80mg/kg; Ro 25-6981 with 3mg/kg and 10mg/kg;Scopolamine with 5ug/kg, 25ug/kg, and 100ug/kg. All the animals firstly exposed to pre-swimming (15 min) followed by acute single-dose drug administration 24 hrs later and tested with second swim (10 min) 24 hrs later. The immobility time for each animal, defined as floating or remaining motionless without leaning against the wall of the cylinder, were scored by researcher, who is blind to this experiment.　　Results:　　For Ketamine group, 30mg/kg Ketamine administration significantly decreased immobility time than that of the Saline group in last 5 min of forced swimming test (P<0.05), instead of 3mg/kg and 80mg/kg Ketamine. Similarly, Ro 25-6981 10mg/kg group exhibited a decreased immobility time than Vehicle group (P<0.05) in the last 5 min of forced swimming test instead of Ro 25-6981 3mg/kg treatment. In addition, Scopolamine 25ug/kg treatment significantly decreased immobility time compared with Saline group (P < 0.05) in last 5 min of forced swimming test, instead of 5ug/kg and 100ug/kg Scopolamine treatment.　　Conclusions:　　Our preliminary data indicated that dose-dependent rapid-onset antidepressant effects were presented in Ketamine (30mg/kg), Ro 25-6981 (10mg/kg), and Scopolamine (25ug/kg), which provided practical does for their future studies.