The effects of chronic losartan pretreatment on restraint stress-induced changes in motor activity, nociception and pentylenetetrazol generalized seizures in rats

Abstract

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.