AMPA receptor–mTOR activation is required for the antidepressant-like effects of sarcosine during the forced swim test in rats: insertion of AMPA receptor may play a role

摘要

Figure 1. Schemata demonstrating the timeline of the experiments for drugs administrations, behavioral tests, and time of sacrifice for western blots analysis. For acute sarcosine administration (A,B), rats were given saline or sarcosine (560 mg/kg, i.p.) once. The forced swim test (FST) was conducted 30 min later (A). At 24 h before FST, rats had a 15-min conditioning swim. To evaluate the general locomotor activity, rats were administrated with saline or sarcosine (560 mg/kg, i.p.) once. The elevated plus-maze test (EPM) was conducted 30 min later (B). Immediately after EPM, rats were sacrificed and then rapidly decapitated. The hippocampus was removed for biochemical analysis (B). For acute sarcosine administration in the absence or presence of mTOR and AMPAR inhibitors (C,D), either AMPA inhibitor (NBQX, 10 mg/kg, i.p.) or mTOR pathway inhibitor (rapamycin, 20 mg/kg, i.p.) was administrated 30 min before sarcosine (560 mg/kg, i.p.) or saline treatment. At 30 min after last injection, rats were then tested in an FST paradigm (C). In a separate study (D), na?ve rats were randomly treated with either AMPA inhibitor (NBQX, 10 mg/kg, i.p.) or mTOR pathway inhibitor (rapamycin, 20 mg/kg, i.p.) was administrated 30 min before sarcosine (560 mg/kg, i.p.) treatment. Thirty minutes after last injection, rats were sacrificed and then rapidly decapitated. The hippocampus was removed for biochemical analysis.