インターフェロン連続投与によるラット自発運動,摂食・摂水行動の減少と脳幹縫線核セロトニン陽性ニューロンの減少

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Recently, repeated administration of interferon (IFN) has been widely applied to the treatment of chronic active hepatitis C. This regimen does, however, have various potentially serious side effects. The untoward effects include psychiatric disorders, most notably depression, as suggested by several recent reports. A disorder involving serotonin metabolism or its receptors in the nervous system (CNS) has been suggested to be related to depression and depressive symptoms. Research into this subject has, however, been minimal in animal models. We quantified the spontaneous behavioral activities of rats during an IFN administration protocol and examined the immunoreactivity of serotonergic neurons of the dorsal raphe nucleus. Twelve male rats, 6～7 weeks old and weighing 203 ± 5 g, were intravenously injected with 1,000 units of IFN once a day for 12 days. Movements of each rat were monitored by Animex. Cumulative spontaneous movements for an entire day began to decrease on the 1st day of IFN administration, and by the 3rd day, had declined to approximately 85% of those observed prior to administration (p<0.05), whereas movements increased (to 110%) in rats injected with physiological saline (controls). Diurnal and nocturnal movements were approximately 90% and 70%, respectively, of the initial values on the 4th day of IFN administration. The decrease was maintained throughout the administration period. The amount of food ingested per day had decreased to approximately 70% of the pretreatment volume by the 4th day (p <0.05), and water ingestion declined steadily reaching approximately half the volume ingested by the saline control rats. The rate of increase in body weight was significantly reduced during IFN administration, as compared with control rats (p <0.05). After treatment with IFN or saline for 12 days, rats were sacrificed and the number of 5-HT positive neurons in the doral raphe nucleus was counted on microscope photographs. The number of serotonin-positive neurons in IFN treated rats was decreased to approximately 1/3 that in the corresponding area of control rats (p < 0.05). Thus, IFN effects manifested in rats as decreases in spontaneous movement and appetite, which were accompanied by a reduction in serotonin-positive neurons in the CNS. The present findings suggest that a reduction in serotonin-positive neurons in the CNS seem to relate with depressive disorder caused by IFN therapy.
東京女子医科大学の論文
1997-02-25

インターフェロン連続投与によるラット自発運動,摂食・摂水行動の減少と脳幹縫線核セロトニン陽性ニューロンの減少

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