腹外側眶皮層參與抗傷害感受與情緒調節(jié)的研究
發(fā)布時間：2018-11-13 13:37
【摘要】：腹外側眶皮層(ventrolateral orbital cortex,VLO)是眶皮層(或眶額皮層,orbital cortex或orbitofrontal cortex)的主要組成,占前額葉皮層(prefrontal cotex,PFC)的大部分區(qū)域。解剖學研究提示VLO可能參與中樞神經系統(tǒng)復雜的功能整合。因為VLO主要接受來自丘腦中央下核(thalamic nucleus submedius,Sm)的投射,并發(fā)出纖維投射到導水管周圍灰質(periaqueductal gray,PAG),因此,VLO作為Sm-VLO-PAG通路中一個的高級中樞,不僅參與痛覺感受,也參與傷害感受性調制;又因為VLO與其它情緒調節(jié)相關腦區(qū)如下丘腦(hypothalamus)、杏仁核(amygdala)等之間的聯系,因此也可能參與情緒調控。本課題研究了:(1)多巴胺及D1、D2樣多巴胺受體在VLO參與的抗大鼠神經病理性疼痛中的作用以及可能的機制;(2)多巴胺及D1、D2樣多巴胺受體在VLO參與的抗大鼠持續(xù)性炎性疼痛中的作用;(3)組蛋白脫乙�；�(histone deacetylases,HDACs)抑制劑VPA微量注射于VLO誘發(fā)的抗抑郁樣行為。結果如下: 1.VLO內微量注射非選擇性多巴胺受體激動劑apomorphine(1.0,2.5,5.0μg)劑量依賴性的減輕大鼠坐骨神經分支損傷模型(spared nerve injury,SNI)引起的觸誘發(fā)痛;D2樣多巴胺受體拮抗劑raclopride(1.5μg)阻滯這一效果,D1樣多巴胺受體拮抗劑SCH23390(5.0μg)則增強上述效果;而D2樣多巴胺受體激動劑quinpirole(0.5,1.0,2.0μg)產生的效應與apomorphine相同;較大劑量(10,20μg)SCH23390也顯著緩解上述觸誘發(fā)痛。進一步研究發(fā)現:VLO內微量注射GABAA受體拮抗劑bicuculline和picrotoxi(n均為200,300 ng)同樣緩解上述觸誘發(fā)痛,而小劑量bicuculline和picrotoxin(100 ng)加強quinpirole(0.5μg)的效果;GABAA受體激動劑muscimol(250 ng)或THIP(1.0μg)阻滯quinpirole(2.0μg)的效果。這些結果說明多巴胺能神經系統(tǒng)參與調節(jié)VLO的抗痛覺超敏作用:激活D2樣多巴胺受體,或者抑制D1樣多巴胺受體均具有抗痛覺超敏作用;GABA能脫抑制作用可能參與D2樣多巴胺受體在神經病理痛中的作用。 2.VLO內微量注射非選擇性多巴胺受體激動劑apomorphine(1.0,2.5,5.0μg)劑量依賴性的抑制大鼠福爾馬林實驗晚時相傷害感受行為;D2樣多巴胺受體拮抗劑raclopride(3.0μg)阻滯上述效應,而D2樣多巴胺受體激動劑quinpirole(1.0,2.0,5.0μg)完全模擬了apomorphine的效應;D1樣多巴胺受體拮抗劑SCH23390(2.5, 5.0, 10μg)則劑量依賴的抑制福爾馬林誘發(fā)的傷害感受行為。這些結果說明D1、D2樣多巴胺受體在VLO參與的抗大鼠持續(xù)性炎性疼痛中的作用不同:D2樣多巴胺受體參與多巴胺引起的抗傷害感受效應,而D1樣多巴胺受體對傷害感受行為具有緊張性易化作用,因此阻滯D1樣多巴胺受體產生抗傷害感受作用。 3.大鼠雙側VLO內微量注射組蛋白脫乙酰基酶(histone deacetylases,HDACs)抑制劑丙戊酸鈉(sodium valproate,VPA,300μg),顯著減少大鼠在強迫游泳實驗(forced swimming test,FST)中的不動(immobility)時間,但并不會對大鼠的自主活動(locomotor activity)行為產生明顯的影響,其效應與慢性腹腔注射SSRIs類抗抑郁劑氟西汀(fluoxetine,10mg/kg,連續(xù)14d)相似。上述結果表明VLO在情緒調控中起一定作用。
[Abstract]:The lateral orbital cortex (VLO) is the main component of the orbital cortex (or the orbitofrontal cortex), which accounts for most of the prefrontal cortex (PFC). The anatomical study suggests that the VLO may be involved in the complex function of the central nervous system. Because the VLO mainly receives the projection from the thalamic nucleus submedius (Sm) from the center of the thalamus, and emits the fibers to the periaqueductal gray (PAG) of the water guide tube, the VLO is used as a high-level center in the Sm-VLO-PAG pathway, not only participating in the pain sense, but also participating in the injury-sensitive modulation; It is also possible to be involved in emotional regulation because of the link between the VLO and other mood-regulating brain regions, such as the hypothalamus (Hypothalamus), amygdala, and the like. (1) The role of dopamine and D1 and D2-like dopamine receptors in the anti-rat neuropathic pain of VLO and the possible mechanism; (2) the role of dopamine and D1, D2-like dopamine receptors in the persistent inflammatory pain of the rats with the participation of VLO; (3) The microinjection of histone deacetylases (HDACs) inhibitor VPA into VLO-induced antidepressants. The results are as follows: 1. The dose-dependence of the non-selective dopamine receptor agonist apomorphine (1.0, 2.5, 5.0. mu.g) in the VLO was dose-dependent in the rat sciatic nerve branch injury model (SNI), and the D2-like dopamine receptor antagonist raclopride (1. 5. mu.g) blocked the one. Effect, D1-like dopamine receptor antagonist SCH23390 (5.0. mu.g) enhanced the above-mentioned effect; while D2-like dopamine receptor agonist quinpirole (0.5, 1.0, 2.0. mu.g) produced the same effect as apomorphine; the larger dose (10, 20. mu.g) of SCH23390 also significantly alleviated the above-mentioned contact It was further found that the microinjection of the GABAA receptor antagonist bicuculline and picrotoxin (n = 200, 300 ng) in the VLO also alleviated the above-mentioned touch-induced pain, while small doses of bicuculline and picrotoxin (100 ng) enhanced the effect of quinpirole (0.5. mu.g); the GABAA receptor agonist, muscimol (250 ng) or THIP (1.0. mu.g), blocked the quinpirole (2.0. mu.g). Effect. These results show that the dopaminergic nervous system is involved in the regulation of the anti-hyperalgesia of the VLO: the activation of the D2-like dopamine receptor, or the inhibition of the D1-like dopamine receptor, has an anti-hyperalgesia effect; the inhibition of the inhibition by the GABA may be involved in the D2-like dopamine receptor in the neuropathic pain Effect of the dose-dependent inhibition of the dose-dependent inhibition of the non-selective dopamine receptor agonist apomorphine (1.0, 2.5, 5.0. mu.g) in the VLO in the presence of a dose-dependent inhibitor of apomorphine (1.0, 2.5, 5.0. mu.g); D2-like dopamine receptor antagonist raclopride (3.0. mu.g) The effect of the above-mentioned effect, while the D2-like dopamine receptor agonist, quinpirole (1.0, 2.0, 5.0. mu.g), completely simulated the effect of apomorphine; D1-like dopamine receptor antagonist SCH23390 (2.5, 5.0, 10. mu.g) inhibited formalin-induced injury. These results indicate that D1, D2-like dopamine receptors play a different role in the anti-rat persistent inflammatory pain involved in the participation of VLO: D2-like dopamine receptors are involved in the anti-injury-receptive effect of dopamine, while the D1-like dopamine receptor has a strain on the sense of injury Sexual facilitation, thus blocking the D1-like dopamine receptor to produce an anti-injury 3. The microinjection of histone deacetylases (HDACs) and sodium vallate (VPA, 300. mu.g) in the double-side VLO of the rat significantly reduced the immobility of rats in the forced swimming test (FST). The time, but does not have a significant effect on the behavior of the rat's autonomic activity, and its effect is related to the chronic intraperitoneal injection of the SSRIs class of antidepressants, fluoxetine, 10 mg/ kg, Continuous 14d) similar. The above results show that VLO is in the mood
【學位授予單位】：西安交通大學
【學位級別】：博士
【學位授予年份】：2010
【分類號】：D919.4
本文編號：2329274
[Abstract]:The lateral orbital cortex (VLO) is the main component of the orbital cortex (or the orbitofrontal cortex), which accounts for most of the prefrontal cortex (PFC). The anatomical study suggests that the VLO may be involved in the complex function of the central nervous system. Because the VLO mainly receives the projection from the thalamic nucleus submedius (Sm) from the center of the thalamus, and emits the fibers to the periaqueductal gray (PAG) of the water guide tube, the VLO is used as a high-level center in the Sm-VLO-PAG pathway, not only participating in the pain sense, but also participating in the injury-sensitive modulation; It is also possible to be involved in emotional regulation because of the link between the VLO and other mood-regulating brain regions, such as the hypothalamus (Hypothalamus), amygdala, and the like. (1) The role of dopamine and D1 and D2-like dopamine receptors in the anti-rat neuropathic pain of VLO and the possible mechanism; (2) the role of dopamine and D1, D2-like dopamine receptors in the persistent inflammatory pain of the rats with the participation of VLO; (3) The microinjection of histone deacetylases (HDACs) inhibitor VPA into VLO-induced antidepressants. The results are as follows: 1. The dose-dependence of the non-selective dopamine receptor agonist apomorphine (1.0, 2.5, 5.0. mu.g) in the VLO was dose-dependent in the rat sciatic nerve branch injury model (SNI), and the D2-like dopamine receptor antagonist raclopride (1. 5. mu.g) blocked the one. Effect, D1-like dopamine receptor antagonist SCH23390 (5.0. mu.g) enhanced the above-mentioned effect; while D2-like dopamine receptor agonist quinpirole (0.5, 1.0, 2.0. mu.g) produced the same effect as apomorphine; the larger dose (10, 20. mu.g) of SCH23390 also significantly alleviated the above-mentioned contact It was further found that the microinjection of the GABAA receptor antagonist bicuculline and picrotoxin (n = 200, 300 ng) in the VLO also alleviated the above-mentioned touch-induced pain, while small doses of bicuculline and picrotoxin (100 ng) enhanced the effect of quinpirole (0.5. mu.g); the GABAA receptor agonist, muscimol (250 ng) or THIP (1.0. mu.g), blocked the quinpirole (2.0. mu.g). Effect. These results show that the dopaminergic nervous system is involved in the regulation of the anti-hyperalgesia of the VLO: the activation of the D2-like dopamine receptor, or the inhibition of the D1-like dopamine receptor, has an anti-hyperalgesia effect; the inhibition of the inhibition by the GABA may be involved in the D2-like dopamine receptor in the neuropathic pain Effect of the dose-dependent inhibition of the dose-dependent inhibition of the non-selective dopamine receptor agonist apomorphine (1.0, 2.5, 5.0. mu.g) in the VLO in the presence of a dose-dependent inhibitor of apomorphine (1.0, 2.5, 5.0. mu.g); D2-like dopamine receptor antagonist raclopride (3.0. mu.g) The effect of the above-mentioned effect, while the D2-like dopamine receptor agonist, quinpirole (1.0, 2.0, 5.0. mu.g), completely simulated the effect of apomorphine; D1-like dopamine receptor antagonist SCH23390 (2.5, 5.0, 10. mu.g) inhibited formalin-induced injury. These results indicate that D1, D2-like dopamine receptors play a different role in the anti-rat persistent inflammatory pain involved in the participation of VLO: D2-like dopamine receptors are involved in the anti-injury-receptive effect of dopamine, while the D1-like dopamine receptor has a strain on the sense of injury Sexual facilitation, thus blocking the D1-like dopamine receptor to produce an anti-injury 3. The microinjection of histone deacetylases (HDACs) and sodium vallate (VPA, 300. mu.g) in the double-side VLO of the rat significantly reduced the immobility of rats in the forced swimming test (FST). The time, but does not have a significant effect on the behavior of the rat's autonomic activity, and its effect is related to the chronic intraperitoneal injection of the SSRIs class of antidepressants, fluoxetine, 10 mg/ kg, Continuous 14d) similar. The above results show that VLO is in the mood
【學位授予單位】：西安交通大學
【學位級別】：博士
【學位授予年份】：2010
【分類號】：D919.4
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