Sarawut LapmaneeNarattaphol CharoenphandhuNateetip KrishnamraJantarima CharoenphandhuMahidol UniversityFaculty of Medicine, Thammasat University2018-06-112018-06-112012-05-16Behavioural Brain Research. Vol.231, No.1 (2012), 20-2818727549016643282-s2.0-84858992258https://repository.li.mahidol.ac.th/handle/20.500.14594/15129Despite being potent anxiolytic agents, benzodiazepines (BDZ) sometimes show reduced therapeutic efficacy in stressed rodents. However, the effectiveness of norepinephrine reuptake inhibitors (NRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) or other anxiolytic interventions, e.g., exercise, remained elusive. Here, we demonstrated that male rats subjected to restraint stress for 4 weeks showed decreases in percent open arm time and open arm entry, as determined by elevated plus-maze test (EPM). Increases in inhibitory avoidance trial 2 and outer zone time were also observed in elevated T-maze (ETM) and open field test (OFT), respectively. To evaluate the anxiolytic-like actions of exercise and anxiolytic drugs, stressed rats were subjected for 4 weeks to swimming or daily gavage with 2. mg/kg diazepam (BDZ), or 10. mg/kg fluoxetine (selective serotonin reuptake inhibitor), reboxetine (NRI), or venlafaxine (SNRI). In EPM, the open arm activity was higher in the swimming, reboxetine-treated and venlafaxine-treated groups as compared to age-matched controls, while diazepam and fluoxetine were without effect. In ETM, a reduction in avo idance latency was observed only in swimming and venlafaxine-treated groups. However, the combined swimming and pharmacological treatment showed no additive anxiolytic-like effect. It could be concluded that restraint stress induced anxiety-like behaviors, which were not responsive to diazepam or fluoxetine, whereas reboxetine, venlafaxine and swimming showed anxiolytic-like actions in stressed rats. © 2012 Elsevier B.V..Mahidol UniversityNeuroscienceArticleSCOPUS10.1016/j.bbr.2012.02.037