大鼠前扣带皮层多巴胺D1受体参与痛相关情绪调节的行为-电生理学观察

本研究旨在探索前扣带皮层(anterior cingulate cortex, ACC)的多巴胺D1受体参与痛情绪反应的调节作用。第一天大鼠适应环境并记录检测指标的基础值;第二天预先在ACC给予多巴胺D1受体拮抗剂SCH-23390或激动剂SKF-38393,然后大鼠左后足底注射完全弗氏佐剂(complete Freund’s adjuvant, CFA, 0.08 mL),与特定环境匹配后建立条件位置逃避(conditioned placeavoidance,CPA)反应;第三天同步观察大鼠在痛环境中的CPA反应与ACC脑区神经元的放电频率,随后进行旷场行为、机械痛行为和热缩足反射潜伏期(paw withdrawal latency, PWL)测试;在另外一组实验中,给予大鼠足底注射生理盐水(NS),ACC脑区预先给予多巴胺D1受体拮抗剂或激动剂,并进行上述同样的实验观察。结果显示：(1)相比于对照组,足底注射CFA的大鼠PWL与机械痛阈值明显降低(P <0.05);(2)注射CFA组的大鼠在“痛环境”和旷场中心的停留时间明显缩短(P <0.05);(3)预先在ACC注射...     

不同时间电针干预痛厌恶大鼠焦虑行为的前扣带皮层机制研究

目的 探究电针干预对痛厌恶大鼠焦虑行为的缓解效应和其对前扣带皮层(anterior cingulate cortex,ACC)N-甲基-D-天冬氨酸(N-methyl-D-aspartate,NMDA)和γ-氨基丁酸(γ-aminobutyric acid,GABA)受体的影响.方法 所有健康大鼠完全随机分为空白(NS...     

痛转化大鼠模型焦虑样情绪行为探索及其前扣带皮层兴奋性变化研究

目的 动态观察痛转化大鼠模型不同时间点机械缩足阈(PWTs)、焦虑样情绪行为及双侧前扣带皮层(ACC)内即刻早期基因(c-Fos)、小清蛋白(PV)的表达变化,探索痛转化大鼠模型诱导焦虑样情绪的时间特征及ACC兴奋性变化。方法 所有实验大鼠随机分为假敏化组和敏化组,敏化组于大鼠左后足足底皮下注射1%角叉菜胶(Car)100μL(第1次),待痛阈恢复至基础水平后,于左侧足背中央注射100 ng/25μL前列腺素E₂(PGE₂)25μL(第2次),建立痛转化模型;假敏化组大鼠第1次注射等量生理盐水,第2次注射等量相同浓度PGE₂。观察痛转化模型大鼠造模前(base)、Car注射后4、24、48、72 h和10 d, PGE₂注射后1、4、24、48、72 h、7 d和14 d的PWTs;分别观察PGE₂注射后24 h、7 d、14 d旷场实验(OF),PGE₂注射后24 h、8 d、15 d高架O迷宫实验(EZM)中大鼠焦虑样行为改变情况。免疫荧光法检测Car...     

虎纹蜘蛛毒素-Ⅰ对大鼠急性内脏疼痛的抑制性效应及与ω-芋螺毒素的比较研究(英文)

研究一种新型的N型电压敏感性钙通道阻断剂虎纹蜘蛛毒素 Ⅰ (HWTX Ⅰ ) ,硬脊膜外腔用药对福尔马林结肠壁粘膜下注射诱导的大鼠急性炎性内脏疼痛的抑制性效应 .5 %福尔马林溶液15 0 μl快速注入SD大鼠乙状结肠壁粘膜下层 ,可产生几种可评估的反映内脏疼痛的固定性行为 .在此伤害性刺激反应前 30min ,经留置的导管向大鼠硬脊膜外腔分别注入各待测药品和试剂 ,观察其对该模型疼痛行为的影响 .与生理盐水阴性对照组 ,美国同类镇痛新药ω 芋螺毒素 (ω CTX MVIIA)和吗啡两个阳性对照组比较 ,HWTX Ⅰ五个剂量组 ,进行大鼠硬脊膜外腔注药 ,均能以剂量依赖方式明显抑制福尔马林结肠壁注射诱导的伤害性行为反应 .HWTX Ⅰ和ω CTX MVIIA在 2 0μg kg体重剂量时 ,其抑制效果是稳定和明显的 ;在 5 0 70 μg kg体重剂量下 ,抑制效果更为显著 .HWTX Ⅰ量 效实验发现 ,在等剂量下 ,ω CTX MVIIA镇痛效果略高于HWTX Ⅰ .但在 5 0～ 75 μg kg较高剂量下 ,ω CTX MVIIA可能引起大鼠产生明显的运动能力障碍 ,而HWTX Ⅰ在该剂量范围内则未见类似的毒副作用 .盐酸吗啡镇痛作用起效快于HWTX Ⅰ和ω CTX MVIIA ,但维持时间较后二者短 .实验结果表明 :同为多肽类N型电压敏感性钙通道拮抗剂 ,HWTX Ⅰ和ω CTX MVIIA大鼠硬脊     

NMDA受体参与小鼠的前额扣带回的神经突触传递

谷氨酸性突触是哺乳动物神经系统的主要兴奋性突触。在正常条件下,大多数的突触反应是由谷氨酸的AMPA受体传递的。NMDA受体在静息电位下为镁离子抑制。在被激活时,NMDA受体主要参与突触的可塑性变化。但是,许多NMDA受体拮抗剂在全身或局部注射时能产生行为效应,提示NMDA受体可能参与静息状态的生理功能。此文中,我们在离体的前额扣带回脑片上进行电生理记录,发现NMDA受体参与前额扣带回的突触传递。在重复刺激或近于生理性温度时,NMDA受体传递的反应更为明显。本文直接显示了NMDA受体参与前额扣带回的突触传递,并提示NMDA受体在前额扣带回中起着调节神经元兴奋的重要作用。     

The facilitatory influence of anterior cingulate cortex on ON-OFF response of tactile neuron in thalamic ventrobasal nucleus

The structures of limbic system have been found to modulate the auditory, visual and pain afferent signals in the related nuclei of thalamus. One of those structures is anterior cingulate cortex (ACC) that influences nocuous response of the pain-sensitive neurons in the ventropostero-lateral nucleus of thalamus. Thus, we inferred that ACC would also modulate tactile information at the thalamic level. To test this assumption, single units were recorded extracellularly from thalamic ventrobasal nucleus (VB). Tactile ON-OFF response and the relationship between different patterns of the responses and the parameters of tactile stimulation were examined. Furthermore, the influence of ACC on the tactile ON-OFF response was studied. ACC stimulation was found to produce a facilitatory effect on the OFF-response of ON-OFF neurons. It lowered the threshold of the off-response of that neuron, and therefore changed the response pattern or enhanced the firing rate of the OFF-response of the neuron. The study on receptive fields of ON-OFF neurons showed that the excitation of the ACC could change an ON-response on the verge of a receptive field into an ON-OFF response. The above results suggest that the ACC modulation sharpens the response of a VB neuron to a moving stimulus within its receptive field, indicating that the limbic system can modulate tactile ascending sensory information.     

The facilitatory influence of anterior cingulate cortex on ON-OFF response of tactile neuron in thalamic ventrobasal nucleus

The structures of limbic system have been found to modulate the auditory, visual and pain afferent signals in the related nuclei of thalamus. One of those structures is anterior cingulate cortex (ACC) that influences nocuous response of the pain-sensitive neurons in the ventropos-tero-lateral nucleus of thalamus. Thus, we inferred that ACC would also modulate tactile information at the thalamic level. To test this assumption, single units were recorded extracellularly from thalamic ventrobasal nucleus (VB). Tactile ON-OFF response and the relationship between different patterns of the responses and the parameters of tactile stimulation were examined. Furthermore, the influence of ACC on the tactile ON-OFF response was studied. ACC stimulation was found to produce a facilitatory effect on the OFF-response of ON-OFF neurons. It lowered the threshold of the off-response of that neuron, and therefore changed the response pattern or enhanced the firing rate of the OFF-response of the neuron. The study on rec     

Long-term potentiation in the anterior cingulate cortex and chronic pain

Glutamate is the primary excitatory transmitter of sensory transmission and perception in the central nervous system. Painful or noxious stimuli from the periphery ‘teach’ humans and animals to avoid potentially dangerous objects or environments, whereas tissue injury itself causes unnecessary chronic pain that can even last for long periods of time. Conventional pain medicines often fail to control chronic pain. Recent neurobiological studies suggest that synaptic plasticity taking place in sensory pathways, from spinal dorsal horn to cortical areas, contributes to chronic pain. Injuries trigger long-term potentiation of synaptic transmission in the spinal cord dorsal horn and anterior cingulate cortex, and such persistent potentiation does not require continuous neuronal activity from the periphery. At the synaptic level, potentiation of excitatory transmission caused by injuries may be mediated by the enhancement of glutamate release from presynaptic terminals and potentiated postsynaptic responses of AMPA receptors. Preventing, ‘erasing’ or reducing such potentiation may serve as a new mechanism to inhibit chronic pain in patients in the future.     

Infusion of methylphenidate into the basolateral nucleus of amygdala or anterior cingulate cortex enhances fear memory consolidation in rats

The psychostimulant methylphenidate (MPD; also called Ritalin) is a blocker of dopamine and norepi-nephrine transporter. It has been clinically used for treatment of Attention Deficit and Hyperactivity Disorder (ADHD). There have been inconsistent reports regarding the effects of systemically adminis-tered MPD on learning and memory, either in animals or humans. In the present study, we investigated the effect of direct infusion of MPD into the basolateral nucleus of amygdala (BLA) or the anterior cin-gulate cortex (ACC) on conditioned fear memory. Rats were trained on a one-trial step-through inhibi-tory avoidance task. MPD was infused bilaterally into the BLA or the ACC, either at ‘0’ or 6 h post-training. Saline was administered as control. Memory retention was tested 48 h post-training. In-tra-BLA or intra-ACC infusion of MPD ‘0’ h but not 6 h post-training significantly improved 48-h memory retention: the MPD-treated rats had significant longer step-through latency than controls. The present results indicate that action of MPD in the BLA or the ACC produces a beneficial effect on the consoli-dation of inhibitory avoidance memory.     

Role of anterior cingulate cortex inputs to periaqueductal gray for pain avoidance

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Genetic and pharmacological studies of GluR5 modulation of inhibitory synaptic transmission in the anterior cingulate cortex of adult mice

In the anterior cingulate cortex (ACC), GluR5-containing kainate receptor mediated the small portion of excitatory postsynaptic current. However, little is known about its role in modulation of neurotransmitter release in this brain region. In the present study, we address this question by using selective GluR5 agonist and antagonist, as well as GluR5(-/-) mice. Our results showed that activation of GluR5 induced action potential-dependent GABA release, which is also required for the activation of voltage-dependent calcium channel and Ca(2+) influx. The effect of GluR5 activation is selective to the GABAergic, but not glutamatergic synaptic transmission. Endogenous activation of GluR5 also enhanced GABA release to ACC pyramidal neurons and the corresponding postsynaptic tonic GABA current. Our results suggest the somatodendritic, but not presynaptic GluR5, in modulation of GABA release. The endogenous GluR5 activation and the subsequent tonic GABA current may play an inhibitory role in ACC-related brain functions.     

Phosphorylated CaMKII post-synaptic binding to NR2B subunits in the anterior cingulate cortex mediates visceral pain in visceral hypersensitive rats

The NR2B subunit of NMDA receptor in the anterior cingulate cortex (ACC) is up-regulated in viscerally hypersensitive (VH) rats induced by colonic anaphylaxis. It plays a critical role in modulation of ACC sensitization and visceral pain responses. Given the key role of calcium/calmodulin-dependent protein kinase II (CaMKII) in synaptic plasticity and behavior learning and memory, we hypothesize that phosphorylation of CaMKII binding to NR2B mediates visceral pain in VH states. We performed in vivo electroporation of CaMKII siRNA produced inhibition of colorectal distension-induced visceromotor response in the VH rats. The NR2B, CaMKII and P-CaMKII-Thr2?? protein levels were increased in 180%, 220% and 304% fold in the post-synaptic density (PSD) fraction in VH rats separately. Western blotting following co-immunoprecipitation showed that P-CaMKII-Thr2?? bound to NR2B in the PSD, which was increased to 267% of control in VH rats. Administration of CaMKII antagonist Antennapedia-CaMKIINtide suppressed visceromotor response in VH rats in parallel with decrease of NR2B levels and reduction of the NR2B-P-CaMKII-Thr2?? protein complex in PSD. In conclusion, CaMKII is a critical signaling molecule in the ACC glutamatergic synaptic transmission and phosphorylation of CaMKII at Thr286, which binds to NR2B subunit at post-synaptic site, modulates visceral pain in viscerally hypersensitive state.