立体定向边缘叶脑白质切开术对大鼠强迫检查行为学改变的影响

目的探讨立体定向边缘叶脑白质切开术对Quinpirole(QNP)引起大鼠强迫性检查行为的影响。方法给大鼠颈部皮下注射QNP建立强迫检查行为动物模型,采用立体定向进行大鼠边缘叶脑白质切开术,在开放场地观察大鼠返“家”频率、平均返回时间、运动总距离、参观地点、参观序列及预期比率,评价大鼠的行为学改变,并与假手术组和氯丙咪嗪处理组对比,观察手术对大鼠强迫检查行为的影响。结果术后2周大鼠返“家”频率及运动总距离与假手术组相比明显减少,平均返回时间延长,参观序列及实际/预期比率出现明显差异,而参观地点没有明显改变。氯丙咪嗪处理可以减弱大鼠过度返“家”次数,延长大鼠平均返回时间,但不影响其他强迫检查行为。结论边缘叶脑白质切开术和氯丙咪嗪处理均能明显改善QNP诱发的大鼠强迫检查行为。     

边缘叶脑炎的临床研究进展

边缘叶脑炎曾被视为是一种与肿瘤相关的难治性罕见疾病,但近期研究发现,它是一种较为常见的自身免疫性疾病,且多与肿瘤无关,临床上表现为迅速进展的短时记忆丧失、精神异常及癫痫发作。许多患者脑脊液呈炎性改变,脑电图(EEG)或磁共振(MRI)检查可发现颞叶有异常表现,免疫检查可检出抗神经元的抗体。若能得到及时的诊断和恰当的治疗,大部分患者的病情可得到改善。     

慢性间断缺氧对老年期大鼠脑白质的影响

目的研究慢性间断缺氧对老年期大鼠脑白质的影响。方法建立老年期SD大鼠慢性间断缺氧模型,免疫组化检测大鼠脑室旁白质髓鞘碱性蛋白（myelin basic protein,MBP）、神经微丝H＋L（neutofilament—H＋L,NF-H＋L）、胶质纤维酸性蛋白（glial fibrillary acidic protein,GFAP）表达并行图像分析;电镜下观察大鼠脑内髓鞘、轴突的超微结构。结果慢性间断缺氧可使老年期大鼠脑白质MBP、NF-H＋L表达减少及GFAP表达增加（P均〈0．05）,MBP与NF-H＋L呈高度正相关（R^2=0．908,P〈0．01）。电镜观察与空白对照组比较,缺氧组大鼠脑内可见较多的髓鞘脱失、轴突受损。结论慢性间断缺氧可对老年期大鼠脑白质产生不良影响,表现为髓鞘脱失、轴突变性以及神经胶质增生。     

尼古丁对帕金森病大鼠纹状体多巴胺及黑质自由基含量的影响

目的 :研究尼古丁对帕金森病大鼠的影响 ,探讨其对 PD的作用机制。方法 :通过 6 - OHDA脑立体定向注射术建立大鼠帕金森病模型。采用生化方法观察不同剂量尼古丁对帕金森病大鼠的作用 ,检测黑质自由基、抗氧化剂及多巴胺含量的变化。结果 :造模前及造模后皮下注射尼古丁的 PD大鼠 ,黑质自由基及抗自由基酶及多巴胺含量较PD组有明显改善 (P<0 .0 5 )。结论 :尼古丁可减轻 6 - OHDA对黑质 DA能神经元的损伤 ,对 PD大鼠具有保护作用     

被动吸烟对大鼠纹状体多巴胺及黑质自由基含量的影响

目的研究被动吸烟对帕金森病(PD)大鼠的影响,探讨其作用机制。方法通过6-羟多巴胺(6-O-HDA)脑立体定向注射术建立大鼠PD模型。术前4周开始被动吸烟及术后持续2周为预防组;术后3周给予被动吸烟持续2周为治疗组。采用生化的方法观察PD大鼠纹状体黑质自由基、抗氧化剂及多巴胺含量的变化。结果吸烟治疗组和吸烟预防组大鼠黑质自由基及抗自由基酶较对照组有明显改善(P<0.05);吸烟预防组PD大鼠纹状体DA含量较对照组有明显改善(P<0.05);吸烟治疗组PD大鼠纹状体DA含量较对照组无变化(P>0.05)。结论被动吸烟能减轻黑质纹状体DA能神经元的损伤。     

杏仁核和扣带回毁损对甲基苯丙胺大鼠边缘区多巴胺受体的影响

目的　探讨立体定向杏仁核和扣带回的联合毁损对甲基苯丙胺 (MAP)大鼠脑内边缘区多巴胺D2受体表达的影响。方法　 4 0只SD大鼠随机分为对照组、MAP组、MAP加毁损组和MAP加假毁损组 ,每组各 10只 ;采用经腹腔注射MAP制备精神分裂症MAP模型 ,立体定向 射频毁损杏仁核和扣带回 ,免疫组织化学ABC法观察边缘区D2受体的表达。结果　与对照组比较 ,MAP组及MAP加假毁损组大鼠边缘区D2受体表达有非常显著性差异(P <0 0 1) ;MAP加毁损组大鼠边缘区D2受体阳性细胞数目与对照组比较无显著性差异 (P <0 0 1)。结论　杏仁核和扣带回的联合毁损可以抑制使用MAP而诱发的边缘区D2表达的亢进。     

高压氧对脑白质疏松大鼠的神经保护作用

目的探讨高压氧对脑白质疏松大鼠的行为学、海马结构及神经元影响。方法采用双侧颈总动脉结扎法制作缺血缺氧脑白质疏松模型,术后2 w脑白质疏松形成。第15天起给予2.0ATA的压力治疗1 h/d,共14 d。定位航行实验、足迹实验观察大鼠行为学变化,HE染色观察大鼠神经元形态学变化,TUNEL法观察凋亡神经元情况。结果与假手术组相比,手术组及高压氧治疗组大鼠认知功能明显减弱,神经元数量减少,排列疏松,胞核固缩,TUNEL阳性细胞增多;与手术组比较,高压氧组认知功能有所改善,神经元数量多且排列整齐。TUNEL法测高压氧组神经元凋亡情况改善。结论高压氧可改善脑白质疏松大鼠海马结构和神经元凋亡情况,且有助于其认知功能的恢复。     

尼古丁对帕金森病大鼠纹状体GDNF和多巴胺含量的影响

目的 研究尼古丁对帕金森病（PD）大鼠纹状体脑胶质细胞源性神经营养因子(GDNF)和多巴胺（DA）含量的影响。方法 将6－羟多巴胺（6－OHDA）立体定向注射到大鼠右侧中脑腹侧背盖部（VTA）和黑质致密部（SNpc)，建立PD大鼠模型。采用生化、免疫组织化学方法观察不同剂量尼古丁对PD大鼠的作用，检测纹状体GDNF表达及DA含量的变化。结果 造模前及造模后皮下注射尼古丁的PD大鼠，纹状体GDNF表达及DA含量较PD组有明显改善（P＜0．05）。结论 尼古丁可减轻6－OHDA对黑质DA能神经元的损伤，对PD大鼠具有保护作用。     

杏仁核毁损对甲基苯丙胺精神分裂症大鼠边缘区多巴胺D2受体的影响

目的探讨立体定向杏仁核毁损对甲基苯丙胺(methamphetamine,MAP)精神分裂症大鼠脑内边缘区多巴胺D2受体表达的影响.方法40只SD大鼠随机分为对照组、模型组、假手术组和手术组,每组各10只;采用经腹腔注射MAP制备精神分裂症MAP模型,立体定向-射频毁损杏仁核,原位杂交法观察边缘区多巴胺D2受体的表达.结果与对照组比较,模型组及假手术组大鼠边缘区多巴胺D2受体表达有非常显著性差异(P＜0.01);手术组大鼠边缘区多巴胺DA受体阳性细胞数目与对照组比较差异无显著性(P＜0.01).结论杏仁核毁损可以抑制使用MAP而诱发的边缘区D2表达的亢进.     

被动吸烟对帕金森病大鼠旋转行为和纹状体多巴胺含量的影响

目的：观察被动吸烟对帕金森病（PD）大鼠的影响,以验证流行病学研究的结论,为PD研制提供一新的线索。方法：用6－羟基多巴胺（6－OHDA）立体定向注入大鼠一侧黑质致密部和中脑被盖腹侧区建立侧侧PD模型,观察术前4周开始始予的被动吸烟（持续6周）和术后2周对成功模型给予的被动吸烟（持续2周）对阿朴吗啡诱发的旋转行为及纹状体DA含量的影响。结果：术前4周开始被动吸烟的大鼠旋转行为有减少趋势,受损侧纹状体DA含量较对照组升高,术后2周,成功模型给予的被动吸烟对PD大鼠的旋转行为及纹状体DA含量均无影响。结论;被动吸烟可减轻6－OHDA对黑质DNA能神经元的损伤。     

High frequency stimulation and temporary inactivation of the subthalamic nucleus reduce quinpirole-induced compulsive checking behavior in rats

Obsessive-compulsive disorder (OCD) represents a highly prevalent and impairing psychiatric disorder. Functional and structural imaging studies implicate the involvement of basal ganglia-thalamo-cortical circuits in the pathophysiology of this disorder. In patients remaining resistant to pharmaco- and behavioral therapy, modulation of these circuits may consequently reverse clinical symptoms. High frequency stimulation (HFS) of the subthalamic nucleus (STN), an important station of the basal ganglia-thalamo-cortical circuits, has been reported to reduce obsessive-compulsive symptoms in a few Parkinson's disease patients with comorbid OCD. The present study tested the effects of bilateral HFS of the STN and of bilateral pharmacological inactivation of the STN (via intracranial administration of the GABA agonist muscimol) on checking behavior in the quinpirole rat model of OCD. We demonstrate that both HFS and pharmacological inactivation of the STN reduce quinpirole-induced compulsive checking behavior. We conclude that functional inhibition of the STN can alleviate compulsive checking, and suggest the STN as a potential target structure for HFS in the treatment of OCD.     

Effects of morphine treatment and withdrawal on striatal and limbic monoaminergic activity and ascorbic acid oxidation in the rat

Since ascorbic acid (AA) reportedly suppresses tolerance to and dependence on morphine in humans and rodents, levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), AA, dehydroascorbic acid (DHAA), uric acid, xanthine, hypoxanthine, glutamate and γ-amino-butyric acid (GABA) were determined by high-pressure liquid chromatography (HPLC) in the striatum and in the limbic forebrain of the rat following morphine treatment (single or repeated) and withdrawal. Single morphine administration (20 mg/kg s.c.) increased DOPAC + HVA/DA, 5-HIAA/5-HT and DHAA/AA ratios, uric acid levels, and decreased xanthine, hypoxanthine, glutamate and GABA levels in both regions. 3-MT levels were decreased in the striatum and increased in the limbic forebrain. After 7 days of morphine treatment, striatal DOPAC + HVA/DA and DHAA/AA ratios and uric acid levels were still higher and striatal and limbic xanthine levels still lower than in controls, while all other parameters were in the range of control values in both regions. Morphine treatment also increased the glutamate/GABA ratio in the striatum. In all morphine-treated rats, individual striatal DOPAC + HVA/DA and DHAA/AA ratio values were directly correlated. After a 48 h withdrawal period, both striatal AA oxidation and glutamate/GABA ratio further increased; limbic 3-MT levels further decreased, while all other parameters did not differ from control values. We conclude that: (i) tolerance to morphine-induced increase in hypoxanthine, xanthine and AA oxidation develops in the limbic forebrain faster than in the striatum; (ii) the morphine-induced increase in striatal and limbic AA oxidation may be considered a consequence of increased formation of reactive oxygen species due to increased DA, hypoxanthine and xanthine oxidative metabolism; (iii) a striatal excitotoxic imbalance characterizes the withdrawal state and may be taken into account to explain the further increase in striatal AA oxidation.     

Stereotactic multi-target limbic leucotomy for treating intractable psychiatric disease in 30 patients☆ Three-year follow-up of memory, intelligence, and psychiatric symptoms

BACKGROUND： The biochemical hypothesis of dopamine hyperfunction in the brain can explain the pathological mechanisms of schizophrenia. Surgery is performed based on limbic system circuit theory correspondence to above-mentioned hypothesis. Stereotactic surgery for the treatment of mental disorders is related to stereotactic surgery that influences the Papez circuit. OBJECTIVE： To observe the effects of stereotactic multi-target limbic leucotomy on the improvements in memory, intelligence and psychiatric symptoms in the treatment of intractable psychiatric disease. DESIGN： Self-control case analysis and follow-up of therapeutic effects. SETTING： Department of Neurosurgery, First Hospital, Hebei Medical University. PARTICIPANTS： Thirty patients with intractable psychiatric disease, who received stereotactic surgery in the Department of Neurosurgery, First Hospital, Hebei Medical University between July 2002 and August 2005, were included in this study. The patients, 21 males and 9 females, all met the diagnostic criteria of intractable psychiatric disease, determined by the national psychosurgery cooperation team in 1998. Informed consents for surgery and clinical follow-up exams were obtained from patients and/or patients＇ relatives （guardians）. METHODS： In 30 patients with intractable psychiatric disease, limbic leucotomy was performed by stereotactic technique. Multi-target radiofrequency hyperthermia was performed in the intracranial amygdaloid nucleus, anterior limb of internal capsule, callosal gyrus, among other regions. The therapeutic effects of patients were evaluated by Brief Psychiatric Rating Scale （BPRS） before surgery, and 6 months, 1, and 3 years after surgery. The Wechsler Adult Intelligence Scale （WAIS） and Clinical Memory Scale （CMS） were used to assess memory and intelligence before and after surgery. MAIN OUTCOME MEASURES： Memory, intelligence, and psychiatric symptoms of patients before and after operation. RESULTS： Thirty patients were included in the final     

Effect of nicotine on quinpirole-induced checking behavior in rats: implications for obsessive-compulsive disorder.

BACKGROUND: Rats treated chronically in a large, open field with the dopamine D2/D3 receptor agonist quinpirole (QNP) develop compulsive checking behavior as defined by a set of behavioral criteria. This paradigm has been suggested as an animal model of obsessive-compulsive disorder (OCD). Because nicotine blocks various behaviors induced by ontogenetic QNP administration, we asked whether nicotine could attenuate QNP-induced compulsive checking. METHODS: Adult male Long-Evans rats (n = 14/group) were treated twice weekly with saline (control), or with QNP (0.5 mg/kg) for 14-16 injections. On the last two injections, rats were pretreated in random order with an acute dose of nicotine (0.3 mg/kg base) or saline 10 min before administration of QNP or saline; and the effects on checking behavior was examined. The effects of chronic QNP treatment on nicotinic receptors in discrete brain regions were also determined. RESULTS: Chronic QNP resulted in compulsive checking and increases in cerebellar alpha4beta2 and alpha7 nicotinic receptor densities. Nicotine pretreatment significantly reduced one of the three measures of compulsive checking behavior. CONCLUSIONS: Nicotine attenuates some symptoms of compulsive checking in a rat model of OCD; however, the mechanisms of this effect and therapeutic efficacy of nicotinic agonists in OCD require further study.     

The effects of ibogaine on dopamine and serotonin transport in rat brain synaptosomes

Ibogaine has been shown to affect biogenic amine levels in selected brain regions. Because of the involvement of these neurotransmitters in drug addiction, the effects of ibogaine on biogenic amine transport may contribute to the potential anti-addictive properties of ibogaine in vivo. With rat brain synaptosomes as our experimental system, we measured the effects of ibogaine on the uptake and release of dopamine (DA) and serotonin (5-HT). Ibogaine competitively blocked both DA and 5-HT uptake with IC50 values of 20 microM at 75 nM 3H-DA and 2.6 microM at 10 nM 3H-5-HT. Ibogaine had no effect on K+-induced release of 3H-DA from preloaded synaptosomes, but 20 microM and 50 microM ibogaine inhibited roughly 40% and 60%, respectively, of the K(+)-induced release of 3H-5-HT from preloaded synaptosomes. In the absence of a depolarizing stimulus, ibogaine evoked a small release of 3H-DA but not 3H-5-HT. These relatively low-potency effects of ibogaine on DA and 5-HT uptake in synaptosomes are consistent with the low binding affinity of ibogaine that has been previously reported for DA and 5-HT transporters. Our results show that if ibogaine modulates DA and 5-HT levels in the brain by directly blocking their uptake, then a concentration of ibogaine in the micromolar range is required. Furthermore, if the anti-addictive effects of ibogaine require this concentration, then ibogaine likely exerts these effects through a combination of neurotransmitter pathways, because binding affinities and functional potencies of ibogaine in the micromolar range have been reported for a variety of neuronal receptors and transporters.     

Differential effects of dopamine agonists on evoked dopamine release from slices of striatum and nucleus accumbens in rats

The effects of dopamine receptor agonists on electrically evoked dopamine release from slices of nucleus accumbens were compared with the effects on release from striatal slices in rats. Apomorphine, which has equal potency at the dopamine D₂ and D₃ receptors, reduced the evoked dopamine release from both regions to the same extent (ED₅₀, 0.42 μM for nucleus accumbens; ED₅₀, 0.46 μM for striatum). Quinpirole of 7-[³H]hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OHDPAT), which are much more potent at the D₃ receptor than at the D₂ receptor, reduced the evoked dopamine release from the nucleus accumbens (ED₅₀, 0.12 μM for quinpirole; 0.02 μM for 7-OHDPAT) much more than the release from the striatum (ED₅₀, 1.6 μM for quinpirole; 0.55 μM for 7-OHDPAT). These results suggest that the contribution of D₃ receptors in nucleus accumbens to regulate dopamine release from dopamine nerve terminals is much greater than that in striatum.     

Measurement of plasmalemmal dopamine transport, vesicular dopamine transport, and K-stimulated dopamine release in frozen rat brain tissue

This report describes experiments designed to (1) establish the specificity of dopamine (DA) transporter (DAT)-mediated plasmalemmal DA transport, vesicular monoamine transporter-2 (VMAT-2)-mediated vesicular DA transport, and K⁺-stimulated DA release in samples prepared from frozen rat striata, and (2) characterize the time-course of the effects of freezing on these processes. The procedure described herein uses a simple method of freezing brain tissue (first cooling in ice-cold buffer and then freezing at −80 °C) that allows for the storage of rat striata followed by the assay of DA transport and K⁺-stimulated DA release using rotating disk electrode voltammetry. Plasmalemmal DA transport into samples prepared from frozen striata was blocked by the DAT inhibitor, cocaine, and vesicular DA transport was blocked by the VMAT-2 inhibitor, dihydrotetrabenazine. Additionally, K⁺-stimulated DA release was Ca⁺²-dependent. Freezing decreases DAT-mediated DA transport, VMAT-2-mediated DA transport, and K⁺-stimulated DA release. However activity is still measurable even after 3 weeks of storage. These results suggest that rat striata retain some DA transport and DA release activity even when stored frozen for a few weeks. Frozen storage of rat striata may thus be valuable for experiments requiring lengthy assays, the accumulation of material, or the transport of samples from one laboratory to another for analysis. These results may also be applicable to the study of frozen human brain tissue.     

神经节苷脂对帕金森病鼠旋转行为、纹状体多巴胺浓度及黑质病理的影响

目的观察神经节苷脂对帕金森病（Ｐａｒｋｉｎｓｏｎｄｉｓｅａｓｅ，ＰＤ）鼠模型的旋转行为、纹状体多巴胺浓度及黑质病理的影响。方法将６－羟基多巴胺用立体定向法注入大鼠一侧中脑被盖腹侧区制作ＰＤ大鼠模型，并于同侧侧脑室注射混合型神经节苷脂（ａｍｉｘｅｄｇａｎｇｌｉｏｓｉｄｅｐｒｅｐａｒａｔｉｏｎ，ＧＭ），观察ＧＭ对由阿朴吗啡所诱发的旋转行为、受损侧纹状体多巴胺浓度及黑质病理的影响。结果ＧＭ能减轻ＰＤ大鼠模型的旋转行为、使受损侧纹状体多巴胺浓度下降和黑质神经细胞减少。结论ＧＭ可减轻６－羟基多巴胺对黑质多巴胺能神经元的损伤。     

Concentrations of dopamine and noradrenaline in some limbic and related regions of the human brain

The concentrations of dopamine and noradrenaline were determined in some limbic, cortical, striatal and mesencephalic regions of 12 humans. The highest concentrations of dopamine were found in the neostriatum and in the nucleus accumbens. Lower but significant values were detected in the globus pallidus, the substantia perforata anterior, the substantia nigra and in the region medial to the substantia nigra (area A 10). The concentrations of noradrenaline were generally low with the highest values in the area A 10 and the substantia perforata anterior.