RESUMEN
We have already reported that ovariectomized (OVX) rats reduced the spontaneous activity during the dark period due to the decease of serotonin release in the amygdala. In this study, we examined the potential of sertraline, a selective serotonin reuptake inhibitor, on the recovery of less spontaneous activity seen in mice with OVX-induced despair-like behaviors. Female 9-week old ICR mice were underwent either OVX or sham surgery. Sertraline (10 mg/kg/day, s.c.) or saline were started to administer to each group for 8 weeks (6 times/week) from the 8th week after OVX. Each spontaneous activity of mouse was evaluated during the dark period (19:00-07:00) using an infrared sensor. Moreover, mRNA expression levels of tryptophan hydroxylase (TPH) and X-box binding protein 1 (XBP1) were measured in the hippocampus and prefrontal cortex using by a real-time PCR method. We found out that the OVX-induced despair-like behaviors were improved by the continuous administration of sertraline. After treatment of OVX, our real-time PCR data showed that sertraline significantly suppressed the upregulation of XBP1 expression levels in both hippocampus and prefrontal cortex, although this suppression of the downregulation of TPH expression levels was seen in only hippocampus. These results suggest that sertraline improves the decrease in spontaneous activity induced by OVX assessed by the hippocampus suppressing decreased serotonin synthesis in the serotonergic neuron.
Asunto(s)
Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Sertralina/farmacología , Animales , Conducta Animal/efectos de los fármacos , Femenino , Ratones Endogámicos ICR , Modelos Animales , Ovariectomía , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Sertralina/administración & dosificación , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGROUND: Decreases in female hormones not only affect bone metabolism and decrease bone mass, but also affect the central nervous system, causing brain disorders such as depression and dementia. Administration of estradiol by hormone replacement therapy can improve dementia, while reduced estradiol in ovariectomized (OVX) model rats can reduce both bone density and locomotor activity. The antidepressant fluvoxamine, which is widely used in clinical practice, can improve this effect on locomotor reduction. Similarly, lactoferrin (LF) can reportedly improve inhibitory locomotion due to stress. OBJECTIVE: In this study, we examined the effect of LF on neurite outgrowth in vitro and in vivo using PC12 cells and rats, respectively. METHODS: We performed an in vivo study in which 8-week-old female OVX rats were administered LF five days a week for 6 weeks from the day after surgery. After administration was completed, spontaneous locomotor activity in the dark period, immobility time in a forced swim test, and release amount of dopamine and serotonin in the brain were measured. RESULTS: LF was found to have a neurite outgrowth function in PC12 cells. Moreover, LF was found to improve OVX-induced decreases in locomotor activity and increases in immobility time in the forced swim test. Furthermore, the administration of LF elicited significant recovery of decreased dopamine and serotonin release in the brains of OVX group rats. CONCLUSION: These results strongly suggest that LF improved OVX-induced decreases in momentum during the dark period and, moreover, that release of dopamine and serotonin in the brain was involved in this effect.