Maternal separation (MS) plays a central role in developing physiology and psychology during the individual ontogeny process. MS is used to research the neurobiological mechanisms of mental disorders and early life stress. In this study, we investigated the effects of repeated MS and early handling (EH) on locomotor activity in an open-field test, a light–dark box test and an elevated plus-maze test of adolescent rats. The results showed that MS reduced locomotor activities in the open-field test, and increased anxiety-like behaviours in the light–dark box test and the elevated plus-maze test in adolescent rats. These tests indicated that early life stress caused by MS might induce anxiety-like behaviours during adolescence. However, compared with the control group, both the MS and EH groups showed conflicting anxiety levels. The results also suggested that females were more prone to showing anxiety-like behaviour compared with males when suffering from high-intensity stimulation. However, because of the low anxiety level associated with EH, the sex difference in behaviour was not significant. The present study provides novel insights into the effects of MS and EH on behaviour, which shows unique anxiety levels different in adolescent male and female rats.

Objective: This research was aimed to evaluate the behaviors of short‐ or long‐term antidepressant effects of ketamine in rats exposed to chronic unpredictable stress (CUS).Background: Ketamine, a glutamate noncompetitive NMDA receptor antagonist, regulates excitatory amino acid functions, such as anxiety disorders and major depression, and plays an important role in synaptic plasticity and learning and memory.Methods: After 42 days of CUS model, male rats received either a single injection of ketamine (10 mg/kg; day 43) or 15 daily injections (days 43–75). The influence of ketamine on behavioral reactivity was assessed 24 hr (short‐term) or 7 weeks after ketamine treatment (long‐term). Behavioral tests used to assess the effects of these treatments included the sucrose preference (SP), open field (OF), elevated plus maze (EPM), forced swimming (FS), and water maze (WM) to detect anxiety‐like behavior (OF and EPM), forced swimming (FS), and water maze (WM).Results: Short‐term ketamine administration resulted in increases of body weight gain, higher sensitivity to sucrose, augmented locomotor activity in the OF, more entries into the open arms of the EPM, along increased activity in the FS test; all responses indicative of reductions in depression/despair in anxiety‐eliciting situations. No significant differences in these behaviors were obtained under conditions of long‐term ketamine administration (p > .05). The CUS + Ketamine group showed significantly increased activity as compared with the CUS + Vehicle group for analysis of the long‐term effects of ketamine (*p < .05). Nor were significant differences obtained in learning and memory performance in rats receiving ketamine (p > .05).Conclusion: Taken together these findings demonstrate that a short‐term administration of ketamine induced rapid antidepressant‐like effects in adult male rats exposed to CUS conditions, effects that were not observed in response to the long‐term treatment regime.

The function of the hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) and the expression of brain-derived neurotrophic factor (BDNF) may be involved in the pathogenesis of post-traumatic stress disorder (PTSD). This study aims to explore the role of the HCN1 channel, BDNF, and mTOR in the actions of PTSD and to examine whether synaptic transmission or plasticity is involved in the regulation of this disease. In the present study, rats were exposed to the single prolonged stress and electric foot shock (SPS&S) procedure, which can induce PTSD-like behaviors in rats. ZD7288 was administered by intracerebroventricular (i.c.v.) injection to one experimental group to inhibit the function of the HCN1 ion channel while 8-Br-cAMP was administered to another group to activate the function of the HCN1 ion channel. A series of behavioral tests and biochemical assessments of certain proteins (HCN1, BDNF, and pmTOR) and synaptic ultrastructure in the prefrontal cortex (PFC) and hippocampus (Hip) were then conducted. The SPS&S procedure induced apparent PTSD-like symptoms in rats. The administration of ZD7288 reduced the immobility time and escape latency time in the forced swim test (FST) and water maze test (WMT) with a decreased level of HCN1, upregulated BDNF-mTOR signaling pathways in the PFC and Hip, and synaptic ultrastructure changes in the PFC. In contrast, the administration of 8-Br-cAMP, which led to a higher level of HCN1 in PFC and Hip, resulted in a decreased number of entries to the open arms without significant change in total arm entries in the elevated plus maze test (EPMT) as well as a shorter center square distance and total distance in the open field test (OFT). Extended escape latency time was also observed in the WMT although there was no alteration of BDNF-mTOR signaling pathways and synaptic ultrastructure in the PFC and Hip. Overall, the inhibition of HCN1, which can alleviate PTSD-like behavior of rats by relieving depression and improving learning ability, may be related to the upregulated BDNF-mTOR signaling pathways and synaptic transmission.