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- 2015
帕金森病大鼠伏隔核神经元电活动变化及5-HT7受体激活的作用
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Abstract:
摘要：目的 研究帕金森病(Parkinson disease, PD)模型大鼠伏隔核(nucleus accumbens, NAc)神经元的电活动变化，以及NAc神经元对5-HT7受体刺激的反应。方法 采用在体神经电生理学和神经药理学相结合的方法，观察PD大鼠NAc神经元的电活动变化以及NAc神经元对5-HT7受体激动剂的反应，并与假手术组进行对比分析。结果 ①PD组大鼠NAc神经元的平均放电频率(5.46±0.88)Hz显著高于假手术组(3.77±0.48)Hz(P<0.05)。PD组大鼠65%的NAc神经元表现为爆发式放电、35%呈不规则放电；假手术组57.5%的NAc神经元呈爆发式放电、42.5%为不规则放电。与假手术组相比，PD组大鼠NAc神经元的爆发式放电比例增多，但差异无统计学意义(P>0.05)。②体循环给予5-HT7受体激动剂AS19后，假手术组大鼠的NAc神经元电活动变化整体上呈现兴奋反应，当累积剂量为160μg/kg时，NAc神经元的兴奋程度明显高于基础放电，且具有统计学意义(P<0.05)；PD组大鼠虽然也表现为兴奋反应，但NAc神经元的兴奋效应在80μg/kg累积剂量时具有统计学意义(P<0.05)，PD组产生统计学意义的累积剂量低于假手术组。AS19所引起的效应能够被特异性5-HT7受体拮抗剂SB269970所反转。结论 NAc神经元5-HT7受体可能介导PD模型大鼠NAc神经元电活动增强效应。
ABSTRACT: Objective To investigate changes in the firing activities of nucleus accumbens (NAc) neurons and their response to 5-HT7 receptor stimulation in a rat model of Parkinson’s disease (PD). Methods The firing activities and response of NAc neurons to 5-HT7 receptor agonist in PD rats were recorded by in vivo electroneurophysiology and neuropharmacology and then were compared with those in the sham group. Results The mean firing rate of NAc neurons was (5.46±0.88)Hz in the sham rats and (3.77±0.48)Hz in the PD rats. The firing rate of NAc neurons increased significantly compared with that in the sham rats (P<0.05). In PD rats, 65% of NAc neurons fired in bursts and 35% fired irregularly. However, in the sham rats, 57.5% of NAc neurons fired in bursts and 42.5% fired irregularly. There was no significant difference in the firing pattern of NAc neurons between the PD and sham rats (P>0.05). Systemic administration of 5-HT7 receptor agonist AS19 increased the firing rate of NAc neurons in the sham and PD rats. This excitation was significant at a high dose of 160 μg/kg for NAc neurons in the sham rats (P<0.05). However, the excitation produced by AS19 was significant at a high dose of 80 μg/kg in PD rats (P<0.05). The cumulative dose-produced excitation in the PD rats was lower than that in the sham rats. The effects induced by AS19 were reversed by the 5-HT7 receptor antagonist SB269970 in both groups. Conclusion The reinforced firing activity of NAc neurons might be mediated by 5-HT7 receptor in the neurons of PD rats
| [1] | AKIMOVA E, LANZENBERGER R, KASPER S. The serotonin-1A receptor in anxiety disorders[J]. Biol Psychiatry, 2009, 66(7):627-635. |
| [2] | KUAN WL, ZHAO JW, BARKER RA. The role of anxiety in the development of levodopa induced dyskinesias in an animal model of Parkinson’s disease, and the effect of chronic treatment with the selective serotonin reuptake inhibitor citalopram[J]. Psychopharmacology (Berl), 2008, 197(2):279-293. |
| [3] | HIGASHINO K, AGO Y, UMEHARA M, et al. Effects of acute and chronic administration of venlafaxine and desipramine on extracellular monoamine levels in the mouse prefrontal cortex and striatum[J]. Eur J Pharmacol, 2014, 729:86-93. |
| [4] | THOMAS DR, MELOTTO S, MASSAGRANDE M, et al. SB656104-A, a novel selective 5-HT<sub>7</sub> receptor antagonist, modulates REM sleep in rats[J]. Br J Pharmacol, 2003, 139(4):705-714. |
| [5] | 赵春禹,徐满英,吕宁.多巴胺对成瘾大鼠伏隔核神经元放电及形态的影响[J].中国临床康复, 2003, 7(10):1489-1491. |
| [6] | BROWN CA, CAMPBELL MC, KARIMI M, et al. Dopamine pathway loss in nucleus accumbens and ventral tegmental area predicts apathetic behavior in MPTP-lesioned monkeys[J]. Exp Neurol, 2012, 236:190-197. |
| [7] | 董建. 多巴胺受体和NMDA受体功能对伏隔核中型棘突神经元兴奋特征的影响[D]. 陕西: 陕西师范大学, 2013. |
| [8] | PAXINOS G, WATSON C. The rat brain in stereotaxic coordinates[M]. Fourth Ed, Sydney: Academic Press, 1995:1-119. |
| [9] | CAO J, LIU J, ZHANG QJ, et al. The selective 5-HT<sub>1A</sub> receptor antagonist WAY-100635 inhibits neuronal activity of the ventromedial prefrontal cortex in a rodent model of Parkinson’s disease[J]. Neurosci Bull, 2007, 23:315-322. |
| [10] | WANG T, ZHANG QJ, LIU J, et al. Firing activity of locus coeruleus noradrenergic neurons increases in a rodent model of Parkinsonism[J]. Neuroscience, 2009, 25(1):15-20. |
| [11] | SATO H, SKELIN I, DIKSIC M. Acute desipramine treatment reduces regional serotonin synthesis rates, while chronic treatment elevates rates, in a rat model of depression: An autoradiographic study[J]. Neurochem Int, 2011, 58(7):759-766. |
| [12] | PEREZ-GGARCIA GS, MENESES A. Effects of the potential 5-HT<sub>7</sub> receptor agonist AS19 in an autoshaping learning task[J]. Behav Brain Res, 2005, 163(1):136-140. |
| [13] | GOLDSTEIN M, LIEBERMAN A, PEARSON J. Relatively high levels of dopamine in nucleus accumbens of levodopa treated patients with Parkinson’s disease[J]. Neural Transmission, 1982, 54:129-134. |
| [14] | ZHANG QJ, LI LB, LIU J, et al. The pyramidal neurons in the medial prefrontal cortex show decreased response to 5-hydroxytryptamine-3 receptor stimulation in a rodent model of Parkinson’s disease[J]. Brain Res, 2011, 1384:69-79. |
| [15] | WANG S, ZHANG QJ, LIU J, et al. Unilateral lesion of the nigrostriatal pathway induces an increase of neuronal firing of the midbrain raphe nuclei 5-HT neurons and a decrease of their response to 5-HT (1A) receptor stimulation in the rat[J]. Neuroscience, 2009, 159 (2):850-861. |
| [16] | TOKARSKI K, ZAHORODNA A, BOBULA B, et al. 5-HT<sub>7</sub> receptors increase the excitability of rat hippocampal CA1 pyramidal neurons[J]. Brain Res, 2003, 993(1-2):230-234 |
| [17] | SARKISYAN G, HEDLUND PB. The 5-HT<sub>7</sub> receptor is involved in allocentricspatial memory information processing[J]. Behav Brain Res, 2009, 202:26-31. |
| [18] | FAN LL, ZHANG QJ, LIU J, et al. <em>In vivo</em> effect of 5-HT<sub>7</sub> receptor agonist on pyramidal neurons in medial frontal cortex of normal and 6-hydroxydopamine-lesioned rats: an electrophysiological study[J]. Neuroscience, 1999, 190:328-338. |
