腹外侧眶皮层参与抗伤害感受与情绪调节的研究
发布时间：2018-11-13 13:37
【摘要】：腹外侧眶皮层(ventrolateral orbital cortex,VLO)是眶皮层(或眶额皮层,orbital cortex或orbitofrontal cortex)的主要组成,占前额叶皮层(prefrontal cotex,PFC)的大部分区域。解剖学研究提示VLO可能参与中枢神经系统复杂的功能整合。因为VLO主要接受来自丘脑中央下核(thalamic nucleus submedius,Sm)的投射,并发出纤维投射到导水管周围灰质(periaqueductal gray,PAG),因此,VLO作为Sm-VLO-PAG通路中一个的高级中枢,不仅参与痛觉感受,也参与伤害感受性调制;又因为VLO与其它情绪调节相关脑区如下丘脑(hypothalamus)、杏仁核(amygdala)等之间的联系,因此也可能参与情绪调控。本课题研究了:(1)多巴胺及D1、D2样多巴胺受体在VLO参与的抗大鼠神经病理性疼痛中的作用以及可能的机制;(2)多巴胺及D1、D2样多巴胺受体在VLO参与的抗大鼠持续性炎性疼痛中的作用;(3)组蛋白脱乙酰基酶(histone deacetylases,HDACs)抑制剂VPA微量注射于VLO诱发的抗抑郁样行为。结果如下: 1.VLO内微量注射非选择性多巴胺受体激动剂apomorphine(1.0,2.5,5.0μg)剂量依赖性的减轻大鼠坐骨神经分支损伤模型(spared nerve injury,SNI)引起的触诱发痛;D2样多巴胺受体拮抗剂raclopride(1.5μg)阻滞这一效果,D1样多巴胺受体拮抗剂SCH23390(5.0μg)则增强上述效果;而D2样多巴胺受体激动剂quinpirole(0.5,1.0,2.0μg)产生的效应与apomorphine相同;较大剂量(10,20μg)SCH23390也显著缓解上述触诱发痛。进一步研究发现:VLO内微量注射GABAA受体拮抗剂bicuculline和picrotoxi(n均为200,300 ng)同样缓解上述触诱发痛,而小剂量bicuculline和picrotoxin(100 ng)加强quinpirole(0.5μg)的效果;GABAA受体激动剂muscimol(250 ng)或THIP(1.0μg)阻滞quinpirole(2.0μg)的效果。这些结果说明多巴胺能神经系统参与调节VLO的抗痛觉超敏作用:激活D2样多巴胺受体,或者抑制D1样多巴胺受体均具有抗痛觉超敏作用;GABA能脱抑制作用可能参与D2样多巴胺受体在神经病理痛中的作用。 2.VLO内微量注射非选择性多巴胺受体激动剂apomorphine(1.0,2.5,5.0μg)剂量依赖性的抑制大鼠福尔马林实验晚时相伤害感受行为;D2样多巴胺受体拮抗剂raclopride(3.0μg)阻滞上述效应,而D2样多巴胺受体激动剂quinpirole(1.0,2.0,5.0μg)完全模拟了apomorphine的效应;D1样多巴胺受体拮抗剂SCH23390(2.5, 5.0, 10μg)则剂量依赖的抑制福尔马林诱发的伤害感受行为。这些结果说明D1、D2样多巴胺受体在VLO参与的抗大鼠持续性炎性疼痛中的作用不同:D2样多巴胺受体参与多巴胺引起的抗伤害感受效应,而D1样多巴胺受体对伤害感受行为具有紧张性易化作用,因此阻滞D1样多巴胺受体产生抗伤害感受作用。 3.大鼠双侧VLO内微量注射组蛋白脱乙酰基酶(histone deacetylases,HDACs)抑制剂丙戊酸钠(sodium valproate,VPA,300μg),显著减少大鼠在强迫游泳实验(forced swimming test,FST)中的不动(immobility)时间,但并不会对大鼠的自主活动(locomotor activity)行为产生明显的影响,其效应与慢性腹腔注射SSRIs类抗抑郁剂氟西汀(fluoxetine,10mg/kg,连续14d)相似。上述结果表明VLO在情绪调控中起一定作用。
[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
【学位授予单位】：西安交通大学
【学位级别】：博士
【学位授予年份】：2010
【分类号】：D919.4
本文编号：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
【学位授予单位】：西安交通大学
【学位级别】：博士
【学位授予年份】：2010
【分类号】：D919.4
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