Pechlivanova Daniela M, Stoynev Alexander G, Tchekalarova Jana D
Institute of Neurobiology, Bulgarian Academy of Sciences, Medical University, Sofia, Bulgaria.
Folia Med (Plovdiv). 2011 Apr-Jun;53(2):69-73. doi: 10.2478/v10153-010-0040-z.
Accumulated evidence has shown that renin-angiotensin system has a pivotal role in stress responses.
to assess the participation of AT1 receptor in stress-induced modulation of motor activity, nociception and seizure susceptibility in male Wistar rats.
AT1 receptor antagonist losartan was administered subcutaneously to rats for 10 days at a dose of 10 mg/kg either alone or as a pretreatment before chronic restraint stress applied for 10 days. Locomotor and exploratory activity (open field test), the nociception (paw-pressure test) and the seizure susceptibility (pentylenetetrazol seizure test) were analysed.
Chronic restraint stress decreased motor activity and increased anxiety-like behaviour (grooming) while losartan pretreatment alleviated anxiety-like behaviour. Chronic restraint stress had an antinociceptive effect in paw-pressure test and losartan pretreatment abolished stress-induced antinociception. Both chronic restraint stress and losartan showed anticonvulsant activity in pentylenetetrazol seizure test. However, drug pretreatment attenuated this effect in chronically-stressed rats.
Our findings suggest that the AT1 receptor is involved in the mechanism of stress-induced changes in anxiety-like behaviour, nociception and seizure susceptibility in rats.
累积证据表明肾素 - 血管紧张素系统在应激反应中起关键作用。
评估AT1受体在雄性Wistar大鼠应激诱导的运动活动、痛觉和癫痫易感性调节中的参与情况。
将AT1受体拮抗剂氯沙坦以10mg/kg的剂量皮下注射给大鼠,单独给药10天,或在施加10天慢性束缚应激前作为预处理给药。分析运动和探索活动(旷场试验)、痛觉(爪压力试验)和癫痫易感性(戊四氮癫痫试验)。
慢性束缚应激降低了运动活动并增加了焦虑样行为(梳理),而氯沙坦预处理减轻了焦虑样行为。慢性束缚应激在爪压力试验中具有抗伤害感受作用,氯沙坦预处理消除了应激诱导的抗伤害感受。慢性束缚应激和氯沙坦在戊四氮癫痫试验中均显示出抗惊厥活性。然而,药物预处理减弱了慢性应激大鼠的这种作用。
我们的研究结果表明,AT1受体参与了大鼠应激诱导的焦虑样行为、痛觉和癫痫易感性变化的机制。