Background:Cisplatin (CP) is a chemotherapy drug, with the major side effect of nephrotoxicity. The level of endothelin-1 (ET-1) increases during nephrotoxicity, which is accompanied with vasoconstrictive properties. Bosentan (BOS) is a nonselective ET-1 receptor antagonist, having vasodilatory and anti-hypertension effects. The purpose of this study was to investigate the renoprotective effect of BOS against CP-induced nephrotoxicity in male and female rats.Materials and Methods:Male and female rats were divided into six groups; groups 1–3 and 4–6 were male and female rats, respectively. Animals in groups 1 and 4 were considered as negative control and groups 2 and 5 considered as positive control groups received BOS (30 mg/kg/day) alone and CP (2.5 mg/kg/day) alone, respectively, for 1-week. The animals in groups 3 and 6 were treated with both CP and BOS. Finally, serum parameters were measured, and the kidney tissue was subjected to staining to evaluate tissue damage.Results:The serum levels of blood urea nitrogen and creatinine, kidney tissue damage score and kidney weight elevated, and body weight significantly decreased in both CP alone and in CP plus BOS-treated groups when compared with the control groups (P < 0.05), while BOS did not ameliorate these parameters neither in males nor in females. No significant differences were observed in serum levels of nitrite and malondialdehyde between the groups, but kidney tissue level of nitrite decreased significantly in CP alone and CP plus BOS-treated groups (P < 0.05).Conclusion:Renoprotective effect of BOS, as ET-1 blocker, was not observed against CP-induced nephrotoxicity neither in male nor in female rats. This is while BOS promoted the severity of injuries in females.

Background and purpose: The central nucleus of the amygdala (CeA) is one of the nuclei involved in the reward system. The aim of the current study was to investigate the electrical stimulation (e-stim) effect of the CeA in combination with dopamine D1 receptor antagonist on morphine-induced conditioned place preference (CPP) in male rats. Experimental approach: A 5-day procedure of CPP was used in this study. Morphine was administered at an effective dose of 5 mg/kg, and SCH23390 as a selective D1 receptor antagonist was administrated into the CeA. In addition, the CeA was stimulated with an intensity of the current of 150 μA. Finally, the dependence on morphine was evaluated in all experimental groups. Findings /Results: Morphine significantly increased CPP. While the blockade of the D1 receptor of the CeA reduced the acquisition phase of morphine-induced CPP. Moreover, the combination of D1 receptor antagonist and e-stim suppressed morphine-induced CPP, even it induced an aversion. Conclusion and implication: The current study suggests that the administration of dopamine D1 receptor antagonist into the CeA in combination with e-stim could play a prominent role in morphine dependence.

The basolateral amygdala (BLA), which is sensitive to stress, is necessary for reward‐seeking behavior and addiction. Regular exercise can produce various positive effects by affecting the BLA. Therefore, we aimed to investigate the effects of chronic stress and treadmill running (TR) on anxiety‐like behavior, neuronal activity, lipid peroxidation (measured by malondialdehyde (MDA) levels, a marker for oxidative stress), and total thiol in BLA, in morphine‐treated rats. Male Wistar rats were restricted in restraint stress and/or ran on the treadmill and treated with morphine (5 mg/kg) for 21 days. Anxiety‐like behavior was evaluated using an elevated plus maze (EPM) and open field tests (OFTs), on day 22. On day 23, neuronal activity in BLA was assessed via single‐unit recording. Finally, MDA and total thiol were assessed in BLA. Our results showed that chronic administration of morphine (5 mg/kg) did not affect anxiety‐like behavior. However, the morphine‐treated rats, subjected to chronic stress and exercise, showed fewer anxiety‐like behaviors. Morphine increased BLA's MDA levels but it was prevented by TR. Glutamatergic and GABAergic basal neuronal activities were low in morphine‐treated rats but after acute morphine application, there was a significant decrease in GABAergic neuronal activities in the morphine‐exercise‐stress (Mor‐Exe‐St) group. The results of this study showed that in morphine‐treated rats, stress and exercise or their combination could have either co‐directional or opposite effects to the chronic effects of morphine. These results indicate the existence of common pathways similar to endogenous opioids.