大鼠伏隔核神经元膜特性及乙醇对其影响

目的:观察伏隔核神经元的膜特性及致醉剂量的乙醇(44 mmol/L)对其影响.方法:在大鼠伏隔核脑片上,采用细胞内电流钳记录技术.结果:所观察到的神经元包括五种类型,神经元的静息膜电位(mV)为-79.1±2.4,输入阻抗(MΩ)为48.4±2.3,锋电位的幅度(mV)平均为98.5±4.1;致醉剂量的乙醇(44 mmol/L)对大部分伏隔核神经元的膜电位、输入阻抗及I/V曲线无明显影响.结论:在伏隔核内,存在多种膜特性类型的神经元;致醉剂量的乙醇对大鼠伏隔核神经元的膜特性无明显影响,说明乙醇对伏隔核神经元的抑制作用主要并不是通过影响膜特性来实现的.     

吗啡成瘾对大鼠伏隔核神经元自发放电的影响

目的 研究吗啡成瘾对大鼠伏隔核电生理的影响及静脉吗啡注射对吗啡成瘾大鼠伏隔核神经元自发放电的影响探讨伏隔核在吗啡成瘾过程中的作用.方法 通过连续14日递增腹腔吗啡注射,建立急性大鼠吗啡成瘾模型,通过玻璃微电极记录吗啡依赖大鼠伏隔核单细胞细胞外放电,观察吗啡成瘾及静脉注射吗啡对大鼠伏隔核神经元放电的影响.结果 与生理盐水组相比,吗啡依赖组大鼠伏隔核神经元单位自发放电的频率分布组间差异显著(P<0.05),放电形式无明显差异.吗啡依赖大鼠伏隔核神经元放电频率静脉注射吗啡前为14.40±4.92Hz,静脉注射吗啡后降为4.10±2.65Hz.结论 吗啡成瘾对大鼠伏隔核神经元自发放电有影响,吗啡可以显著抑制吗啡成瘾大鼠的伏隔核神经元放电,伏隔核在吗啡成瘾过程具有重要作用.     

神经性厌食症大鼠伏隔核神经元局部场电位分析

目的观察神经性厌食症大鼠模型伏隔核神经元的电活动并分析其局部场电位。方法实验动物分为运动诱发的厌食症(activity-based anorexia,ABA)大鼠模型组及对照组(各12只)。ABA模型的建立基础是模型大鼠不受限制的滚轮运动以及限制饮食(1h/d),通过这种限制饮食及过度活动,造成明显的体重下降,从而模拟AN的行为学特征。通过微阵列电极记录大鼠在神经性厌食症病理及正常生理状态下伏隔核神经元的局部场电位。结果电生理记录显示模型组大鼠NAc神经元平均放电频率为(6.89±2.67)Hz,对照组为(3.22±1.23)Hz。模型组大鼠伏隔核神经元放电的峰峰间期散点图在200ms以下有密集分布。模型组伏隔核神经元放电峰峰间期直方图呈逐渐衰减的正偏态分布,对照组伏隔核神经元放电峰峰间期直方图呈对称分布;回归映射分析结果显示病理状态下数据明显较生理状态下集中。功率谱密度分析显示模型组在10~20Hz范围内出现了能量高值成分。结论神经性厌食症模型大鼠伏隔核神经元较生理状态下放电频率明显增加,峰峰间期序列发生明显变化,局部场电位模式发生变化。     

GABA对大鼠伏隔核痛反应神经元电活动的影响

目的在50只成年Wister大鼠上，观察了侧脑室(icv)注射GABA(γ-氨基丁酸)后，伏隔核(NAc)痛反应神经元放电的变化和荷包牡丹碱(Bic)对GABA作用的阻断效应，从而进一步研究GABA与NAc在痛觉调制中的作用。方法采用icy注射，电脉冲强直刺激坐骨神经作为伤害性痛刺激，玻璃微电极细胞外记录痛反应神经元放电的变化。结果(1)icv注入GABA能够使正常大鼠NAc中痛兴奋神经元(PEN)痛诱发放电频率减少、潜伏期延长，而使痛抑制神经元(PIN)痛诱发放电频率增加、诱发放电完全抑制时程缩短；(2)icv注入GABAA受体拮抗剂Bic能够阻断GABA的上述效应。结论(1)外源性GABA可使正常大鼠NAc中痛反应神经元对伤害性刺激的反应减弱，表现为镇痛效应；(2)GABA的这种镇痛作用主要是通过GABAA受体介导的。该结果揭示，GABA和NAc在痛觉调制中具有非常重要的作用。     

毁损伏隔核、扣带回前部对海洛因成瘾大鼠觅药行为的影响

目的探讨伏隔核和扣带回前部在药物强化效应中的作用。方法分别毁损海洛因成瘾大鼠双侧伏隔核、扣带回前部,利用条件性地点偏好实验测定术前、术后成瘾大鼠对注射海洛因的偏好分,评价伏隔核和扣带回前部在药物强化效应的作用。结果毁损大鼠双侧伏隔核能够完全消除条件性地点偏好,毁损扣带回前部明显减少条件性地点偏好。术后未见明显副作用及并发症。结论伏隔核和扣带回是调节强化作用的重要位置;本实验为阐明药物依赖机制及指导临床药物依赖的治疗提供一定的参考。     

立体定向毁损伏隔核组合治疗精神分裂

目的 观察立体定向手术方法毁损伏隔核组合治疗精神分裂的疗效.方法 对7例难治性精神分裂的病人行立体定向手术毁损伏隔核组合扣带回、杏仁核,观察其疗效.结果 1例痊愈,6例显效,6例抗精神病药物效价增高而出院.术后1例强迫症复发.术后经6～22个月的随访,6例显著进步.结论 伏隔核组合毁损可改善病人阳性症状、可提高抗精神病药物药物效价.伏隔核可能是治疗精神分裂的有效靶点之一.     

立体定向手术干预伏隔核治疗神经性厌食症

目的通过立体定向毁损术及脑深部电刺激能有效治疗神经性厌食症。方法共8例罹患神经性厌食症的患者通过立体定向手术干预伏隔核治疗神经性厌食症（其中6例患者接受双侧伏隔核毁损术,2例患者接受双侧伏隔核脑深部电刺激）。患者术前均接受正规的抗精神类药物及心理、营养治疗无效。患者术前及术后接受BMI指数、YBOCS,HAMA,HAMD量表的测定,评价疗效。结果 8例患者术后BMI指数均得到明显改善（P〈0.01）,除1名患者外,其余患者BMI指数均大于18.5kg/m^2。接受双侧伏隔核毁损术的患者术后YBOCS,HAMA,HAMD指数均得到立即改善,接受双侧伏隔核脑深部电刺激的患者术后经过程控,各项评定也均得到有效控制。结论伏隔核是治疗神经性厌食症的有效靶点,立体定向手术干预伏隔核可有效改善神经性厌食症患者的各项症状。     

术中电刺激伏隔核的临床观察(附41例临床分析)

目的总结术中电刺激伏隔核时患者的反应,探讨伏隔核毁损术的有效性和安全性。方法共行双侧伏隔核毁损术41例,其中包括海洛因成瘾35例、癫痫致精神障碍3例、伴攻击行为精神发育迟滞1例、躁狂症1例。术中应用采用深圳安科ASA601-T射频热凝器行靶点毁损前进行运动刺激和感觉刺激,观察和记录电刺激伏隔核时患者主观感受及生命体征变化,术后复查头颅MRI了解。结果测量电阻为400~560Ω,用一定参数的电流刺激时病人立即出现口周麻木,烦躁、全身发热感、头面部冒出粗大汗珠,心率下降,出现不同程度的类似吸毒的欣快感,术后复查头颅MRI提示靶点准确。结论术中电刺激伏隔核仔细观察病人特异反应能更准确地对伏隔核进行定位,从而保证手术的有效性和安全性。     

高频电刺激伏隔核对吗啡诱导大鼠条件性位置偏爱行为的影响

目的研究高频电刺激伏隔核(nucleus accumbens,NAc)对吗啡诱导戒断大鼠觅药行为的影响,分析NAc在大鼠成瘾行为中的作用。方法26只雄性SD大鼠通过吗啡强化形成条件性位置偏爱后,13只予以120Hz高频电刺激伏隔核(吗啡刺激组),另13只予以假刺激(吗啡假刺激组)。15d后给予注射吗啡,诱导大鼠恢复位置偏爱行为,测量并比较两组的位置偏爱得分。结果吗啡电刺激组大鼠在注射吗啡诱导下不易恢复对吗啡的条件性位置偏爱,位置偏爱得分为(237.59±79.89)s,吗啡假刺激组为(441.29±212.68)s,两组比较,差异有统计学意义(P<0.01)。结论电刺激NAc能阻断注射吗啡诱导戒断大鼠恢复觅药行为。在成瘾药物诱导戒断动物觅药行为的过程中,NAc起重要作用。     

酒精对大鼠伏核诱发电位的抑制

电刺激大鼠脑片嗅结节区,记录伏核神经元的诱发电位,观察酒精对该诱发电位的影响。并用氯胺酮和Ｌ－谷氨酸进行分析。结果表明：酒精能使伏核神经元诱发电位的幅值降低２２．１％,同时酒精亦能使外源性谷氨酸引起的诱发电位幅值降低３２．７％。提示酒精抑制伏核神经元的诱发电位可能与ＮＭＤＡ受体有关。     

Intracellular recordings from rat nucleus accumbens neurons in vitro

Intracellular recordings were obtained from rat nucleus accumbens (NAC) neurons in brain slice preparations. Local stimulations evoked depolarizing postsynaptic potential (DPSP). Injections of low intensity depolarizing currents decreased the amplitude of the DPSP and reversed a later portion of the DPSP into a hyperpolarizing potential. Superfusion of pentobarbital facilitated the reversal of this later portion of DPSP and bicuculline abolished this polarity reversal. These data suggested that the DPSP evoked by local stimulation consisted of a combination of an excitatory and an inhibitory postsynaptic potential, and that the latter was probably mediated by gamma-aminobutyric acid.     

Myorelaxant effect of baclofen injected to the nucleus accumbens septi

Summary The GABAergic modulation in the nucleus accumbens septi (NAS) of muscle tone was investigated in rats using behavioral tests. The GABA_B receptor agonist baclofen dose-dependently decreased muscle tone in the wiremesh and bar holding tests both after local injection into the NAS (1.0 and 2.5 g), and after intraperitoneal administration in a dose of 20 mg/kg. In the Wirth's test haloperidol (5 mg/kg i.p.), produced catalepsy, whereas baclofen (20 mg/kg, i.p.) significantly deteriorated rats' performance. Intraaccumbens microinjections of muscimol, midazolam, nicardipine, as well as peripheral injections of haloperidol and midazolam failed to modify muscle tone in the wire-mesh test. These findings argue against the involvement of GABA_A receptors, benzodiazepine receptors, as well as dopaminergic- and calcium channel-related mechanisms in the effect of baclofen. Hence, the muscle relaxant effect of baclofen seems to be also mediated through GABA_B receptor sites within the NAS.     

Mapping of locomotor behavioral arousal induced by microinjections of dopamine within nucleus accumbens septi of rat forebrain

Dopamine (DA) at ca. ED₅₀ (16 μg) or saline was stereotaxically microinjected unilaterally 2 h after pretreatment with an MAO inhibitor into left or right nucleus accumbens septi of 697 freely moving rats (1394 injections) to define subregions involved in DA-induced behavioral arousal throughout the anatomical extent of the accumbens. Locomotion was quantified electronically and behavioral responses were assigned to histologically verified injection sites; postural or stereotyped behaviors characteristic of DA injections in caudate-putamen did not occur. Screening with 60 injections across mid-accumbens (2.2–3.2 mm rostral to bregma) indicated that locomotion was elicited non-homogeneously, and was particularly intense dorsomedially. Sites yielding intense arousal and their inactive surround were mapped along the rostrocaudal axis (1.4–4.2 mm anterior to bregma) in coronal sections. Responses to DA showed lateral symmetry and were similar across rostrocaudal levels, with intense responses in dorsomedial accumbens along its border with the caudate-putamen. This functional localization does not coincide closely with reported distributions of DA or its receptors, nor with histologically or histochemically defined core-shell regions of this limbic structure. Nucleus accumbens in rat brain thus appears to be organized functionally into distinct subregions differing markedly in ability to produce locomotor hyperactivity in response to exogenous DA.     

Repeated ethanol exposure during adolescence alters the developmental trajectory of dopaminergic output from the nucleus accumbens septi

Individuals who begin using alcohol prior to 14 years of age are 4 times more likely to progress to addiction than those who do not initiate use until 21 years of age. The nucleus accumbens septi undergoes dramatic developmental transitions during the adolescent period, and dopaminergic activity within this region has been identified as a central neurochemical mediator of drug reward, addiction and dependence. Thus, alcohol-induced neurochemical alterations in dopaminergic activity within this brain region likely mediate the heightened vulnerability to addiction observed in adolescent alcohol users. To investigate this idea, Sprague–Dawley rats were exposed to intraperitoneal injections of either saline or ethanol (0.5, 1.0 or 2.0 g/kg) twice daily over four days beginning on postnatal day 21, 31, 41 or 56. Cannulas were implanted toward the nucleus accumbens septi, subsequent in vivo microdialysis was used to collect samples, and both basal and ethanol-stimulated dopamine overflow was measured using high performance liquid chromatography with electrochemical detection. A developmental transition in basal levels of dopamine in the nucleus accumbens septi was apparent with peak levels at postnatal day 45. An ethanol challenge produced unique responses across ages, with greater peak effects relative to baseline in younger animals (postnatal day 25 and 35). Following repeated exposure to ethanol, a significant increase in basal dopamine was apparent for all ages, and when these animals were challenged with ethanol, peak effects relative to baseline were decreased in younger animals, but unchanged in older animals (postnatal day 45 and 60). Results indicate that there is a key developmental transition in the ability of rats to adapt to the effects of repeated ethanol exposure, which occurs between postnatal day 35 and 45. This alteration may explain the increased addiction vulnerability observed in individuals who initiate alcohol use during early adolescence.     

Changes in dendritic spine density in the nucleus accumbens do not underlie ethanol sensitization

Behavioral sensitization to various drugs of abuse has been shown to change dendritic spine density and/or morphology of nucleus accumbens (NAc) medium spiny neurons, an effect seen across drug classes. However, is it not known whether behavioral sensitization to ethanol (EtOH) is also associated with structural changes in this region. Here we compared dendritic spine density and morphology between mice showing High vs. Low levels of EtOH sensitization and found that high levels of EtOH sensitization were not associated with changes in dendritic spine density or spine type. Unexpectedly, however, a significant increase in the density of stubby‐type spines was seen in mice that were resistant to sensitization. Since the presence of this spine type has been associated with long‐term depression and cognitive/learning deficits this may explain why these mice fail to sensitize and why they show poor performance in conditioning tasks, as previously shown. A possible causal role for structural plasticity in behavioral sensitization to various drugs has been debated. In the case of EtOH sensitization, our results suggest that drug‐induced changes in structural plasticity in the accumbens neurons may not be the cause of sensitized behavior. Synapse 69:607–610, 2015 . © 2015 Wiley Periodicals, Inc.     

Distribution of amygdala input to the nucleus accumbens septi: An electrophysiological investigation

Summary The nucleus accumbens septi (NAS) receives afferent input from the amygdala via the stria terminalis and from the hippocampus via the fimbria. Extracellular recordings from 196 NAS neurons in halothane-anesthetized rats revealed heterogeneous response patterns following stimulation of the amygdala. The observation that 30% of anterior NAS units but only 16% of posterior NAS units were responsive to amygdala stimulation suggested a topographical arrangement of amygdala efferents. Comparing the effects of amygdala and fimbria stimulation revealed that the two afferent pathways converge onto individual NAS neurons, but that the two sites of stimulation can differentially influence other neurons. The present results clarify the topographical distribution of amygdala input to the NAS, confirm that inputs from two limbic structures are integrated within the NAS, and further illustrate the electrophysiological heterogeneity of NAS neurons.     

The electrophysiological effects of neurotensin on spontaneously active neurons in the nucleus accumbens: an in vivo study

Considerable evidence obtained from neuroanatomical and neurochemical studies suggests an interaction between the endogenous tridecapeptide neurotensin (NT) and central nervous system dopamine (DA) neurons. Centrally administered NT blocks many of the actions of synaptic DA in limbic brain areas; the specific mechanism and receptors involved remain under investigation. The electrophysiological effects of NT were studied using extracellular recording techniques and iontophoretic application in 243 spontaneously active neurons in the nucleus accumbens (NAc), with a positive/negative waveform. NT was directly applied to 208 neurons in a pulsatile fashion by iontophoresis (21+/-1 nA). NT had no effect on the firing rate of 120 neurons ((0.31+/-0.72)%), decreased the firing rate in 51 neurons ((-27.87+/-1.52)%), and increased the firing rates of 37 neurons ((33.38+/-2.6)%). One hundred ninety nine (81.9%) of the neurons studied were sensitive to iontophoretically applied DA (>15% decrease in firing rate). The effects of continuous NT application on DA-induced inhibitions were studied in 169 neurons. NT attenuated neuronal responses to directly applied DA by (49.95+/-4.52)%, with antagonism in the "core" subregion (n=96) of (33.41+/-7.75)% when compared with antagonism in the "shell" subregion (n=71) of (61.39+/-5.2)%. The effects of NT on DA were consistent and independent of the effects of NT alone. These data provide further evidence that NT functions as a true neuromodulator in the NAc, exerting minimal direct effects, but blocking the actions of DA.