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1. The present study examined the effect of naloxone (NAL), glycyrrhizic acid (GCA), deoxycorticosterone (DOC) and dexamethasone (DEX) on daily repeated 2 h chronic restrained stress (RS) on the locomotor activity (LA) of rats tested in the open field arena to elucidate the possible roles of opioids, glucocorticoids and mineralocorticoids in response to stress.2. Intact and adrenalectomized (ADX) rats were either injected with 0.1 mL of NAL (0.32 µg/100 g BW), 2.4 mg/kg DOC or 120 µg/kg DEX or had 1.0 mg/mL GCA dissolved in their drinking water or normal saline (for the ADX group) dissolved in their drinking water.3. In intact groups, treatment with NAL completely blocked the stress response and treatment with GCA, DOC and DEX partially prevented the stress response. Adaptation occurred on either days 4, 5, 6 or 7 for intact rats treated with DEX, DOC, GCA or control rats, respectively. All ADX control rats died following the first 2 h RS. Adrenalectomized rats treated with DEX or DOC adapted later compared with intact rats, while rats given either GCA or NAL were unable to block or adapt to chronic RS.4. These findings demonstrate that the stress response is primarily mediated by endogenous opioids, in that it is blocked by NAL. Both mineralocorticoids and glucocorticoids, which can act centrally to inhibit endorphins, partially blocked the stress response. The effect of GCA in intact rats was similar to that of both DEX and DOC in intact rats. Adrenalectomized rats treated with GCA (despite their lack of endogenous corticosterone) showed a stress response that was significantly different from the other ADX groups, implying that GCA had effects independent of endogenous corticosterone.