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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, reg-

As an adverse form of early-life stress (ELS), maternal separation (MS) can interfere with the development of cognition and behaviors of adolescent rodents. Brain-derived neurotrophic factor (BDNF) is involved in the regulation of brain development and function, but the molecular mechanisms by which BDNF regulates brain function and behavior in MS with different stressor strengths remain unclear. This descriptive study characterized the levels of BDNF in the prefrontal cortex (PFC) and plasma corticosterone (CORT) from the offspring of rats exposed to early handling (EH, 15-min separation per day) and prolonged MS (PMS, 180-min separation per day), during postnatal days (PND) 1-21. The behavioral and biochemical analyses were performed during adolescence (PND 42-56). PMS resulted in reduced weight and decreased locomotor activity in the open field test and Y-maze task compared to control (CON) group, with EH showing an intermediate phenotype. BDNF protein levels in the PFC were lower in PMS compared to EH and further reduced in CON male rats. Plasma CORT levels were higher in PMS compared to CON with EH again showing intermediate levels. Neither PMS or EH affected spatial learning in the Y-maze task. These findings indicate that longer periods of maternal separation are necessary to increase anxiety-like behavior, elevate CORT levels, and further suppress BDNF levels in the PFC, providing a possible mechanism to explain why more severe forms of ELS lead to more significant psychiatric and medical consequences later in life.

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