利用習得無助憂鬱症動物模式來研究食慾素系統在憂鬱症扮演的角色
2016
Hochschulschrift
Zugriff:
104
In recent years, many studies have shown that orexin system not only regulate sleep and appetite, but also regulate behaviors in animal model of depression, including activity, learning, memory, and fear behaviors. Similar physiological and behavioral dysfunctions were also seen in depression patients. Growing evidences from preclinical and clinical studies suggest that orexin (Ox) and orexin receptor (Ox R) are involved in the pathophysiology of depression. Previous studies have noted that stress increases the activation of Ox neurons. In the present studies, we used male Sprague-Dawley (SD) rats, and we used foot shocks in the shuttle box to select animals displaying learned helplessness (LH) and no learned helplessness (NoLH) behaviors to simulate helplessness symptoms of depression patient. We investigated whether the number and activation of Ox neuron in the hypothalamus of LH and NoLH rats were different. We also observed Ox A, B and Ox R-1/2 protein expression in regions related to depression, as well as Ox concentration in the serum. In another experment, LH rats were given bupropion antidepressant (20mg/kg/day) or vehicle (control group) injections for 12 days, and to observe whether the number and activation of Ox neurons were different in treatment responsive and resistant rats. We found that LH rat showed lower number of Ox A neurons and reduced Ox A activation in the hypothalamus, as well as a lower concentration of Ox A but higher concentration of corticosterone in the serum compared with that of NoLH rats. In addition, in brain regions related to depression, we found the LH rats had lower Ox A protein levels in the dentate gyrus of hippocampus whereas Ox B protein levels were higher in the amygdala and paraventricular nucleus of the thalamus (PVT). Furthermore, the Ox R-1 expression was higher in the amygdale but lower in the ventral tegmental area (VTA). These changes might associated with fear and anxiety-like behaviors. In the antidepressant experiment we found that bupropion could reverse foot shock induced reduction in sucrose consumption, which indicated anhedonic behavior. However, the antidepressant treatment only reversed the LH behavior in a subgroup of rats (responsive). In addition, we found that there was an increase in Ox A neurons in the hypothalamus of treatment responsive rats and their serum Ox A concentration were also higher. These changes were similar to NoLH rats. In conclution, we think the orexin system is related to learned helplessness behaviors, in particular, Ox A activation could reduce depression-like behaviors.
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利用習得無助憂鬱症動物模式來研究食慾素系統在憂鬱症扮演的角色
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Autor/in / Beteiligte Person: | Hsu, Chung-Wei ; 徐仲緯 |
Link: | |
Veröffentlichung: | 2016 |
Medientyp: | Hochschulschrift |
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