Eiji Itoh

Behavioral characteristics of SART-Stressed mice in the forced swim test and drug action

SART-stressed (repeated cold-stressed) mice exhibited shortened immobility time in forced swimming tests, and a time-dependent increase in the duration of immobility time of stressed mice was less compared to unstressed mice. These changes were blocked by diazepam and alprazolam without influence on the immobility time of unstressed mice. The shortening of immobility time caused by SART stress was inhibited by repeated pretreatment with imipramine and mianserin, but not by a single dose. In contrast, neither single nor repeated administrations of lithium carbonate had effect on the immobility time of SART-stressed mice. The SART stress technique may be a potential model to investigate the relationship between stress and depression with complex symptoms like excessive emotion- and anxiety-related depression.

Platelet hypoaggregability in rats exposed to SART stress (repeated cold stress)

A prolongation of bleeding time accompanied by thrombocytopenia and abnormalities in coagulation-fibrinolysis systems has been observed in laboratory animals exposed to a chronic form of environmental stress induced by severe fluctuations of air temperature, known as SART (specific alternation of rhythm in temperature) stress. In order to clarify the hemostatic profile under SART stress in more detail, the present study examined platelet aggregability in vitro as well as in vivo in stressed rats. During exposure to stress, thrombocytopenia developed from day 5, and remained up to at least day 14. In vitro aggregation of platelets stimulated by ADP or collagen was markedly decreased in stressed rats, compared with unstressed rats. Furthermore, stressed rats exhibited in vivo hypoaggregability of platelets, as estimated by the magnitude of the drop in circulating platelet counts following intravenous injection of ADP and collagen. Protein and cholesterol content in platelets remained constant after stress exposure. These results indicate that SART-stressed rats exhibit platelet dysfunctions in addition to thrombocytopenia. Considering the previous findings, the hemostatic system under SART stress appears to show a general tendency toward hemorrhage.

Effects of the α1-adrenoceptor agonist phenylephrine on SART stress-induced orthostatic hypotension in rats

BackgroundSpecific alternation of rhythm in temperature (SART)-stressed rats, an animal model of autonomic imbalance, exhibit low blood pressure and tachycardia during consciousness and under anesthesia. In addition, these rats easily develop orthostatic hypotension (OH) as a response to postural manipulation. Hence, we studied the influence of the adrenalin α1-receptor agonist phenylephrine on stress-induced OH in SART-stressed rats and unstressed rats.MethodsMale Wistar rats weighing 250-300 g were used. Rats were fixed in the supine position under urethane anesthesia. Blood pressure was directly measured from the left common carotid artery and ECG was recorded simultaneously.ResultsThe maximum decrease in blood pressure and the area under the blood pressure-time curve were both large, while the %reflex was small in the SART-stressed rats compared with unstressed rats. In the SART-stressed rats, prolonged intravenous administration of phenylephrine reduced OH at a dose that barely affected unstressed rats.ConclusionThe results suggested that sympathetic dysfunction is a factor underlying SART stress-induced OH.