计算机辅助下立体定向颅内多靶点毁损治疗难治性精神分裂症的疗效观察及护理

目的观察计算机辅助立体定向技术和颅内多靶点组合毁损治疗难治性精神分裂症的临床疗效。方法80例难治性精神分裂症病患者,均予计算机辅助下立体定向颅内多靶总毁损治疗,并予围术期护理,观察手术效果。结果80例患者显著进步43例,进步33例,无效4例,加重0例,总有效率为95％。患者术后无严重并发症和后遗症发生。结论计算机辅助立体定向颅内多靶点毁损治疗难治性精神病安全有效,注重围术期护理能有效降低其术后并发症,显著提高疗效。     

利培酮治疗汉族精神分裂症患者时血药浓度与临床疗效的关系

目的 探讨利培酮治疗汉族精神分裂症患者时利培酮和代谢产物9-羟利培酮血药浓度与临床作用的关系.方法 采用开放、自身对照研究.入组精神分裂症患者363例,男性195例,女性168例.用临床总体印象量表(CGI-S、CGI-I)评价疾病严重程度和疗效.结果 [1]利培酮血药浓度为(9.70±10.24)μg·L-1,9-羟利培酮浓度为(31.07±18.02)μg·L-1,总浓度为(40.77±23.22)μg·L-1.女性患者血药浓度显著高于男性.[2]利培酮、9-羟利培酮及总血药浓度与CGI-I之间均未发现显著性的相关.治疗有效组(191例)与无效组(172例)相比,2组在剂量、药物血药浓度等方面的差异均无统计学意义.[3]锥体外系反应(EPS)组的平均病程及平均住院次数显著少于无EPS组.结论 利培酮治疗汉族精神分裂症患者时,女性患者浓度显著高于男性,与疗效之间未见显著相关性.     

阿立哌唑口腔崩解片与阿立哌唑片治疗精神分裂症对照研究

目的:比较阿立哌唑口腔崩解片与阿立哌唑片治疗精神分裂症的疗效和安全性.方法:将120例精神分裂症患者随机分为研究组(阿立哌唑口腔崩解片治疗组)60例和对照组(阿立哌唑片治疗组)60例.研究组阿立哌唑口腔崩解片10-30mg/d,对照组阿立哌唑片10-30ms/d,疗程均为8周.在治疗前及治疗后第2、4、8周末使用PANSS评定临床疗效、使用TESS评定药物不良反应,进行比较分析.结果:阿立哌唑口腔崩解片的治疗有效率为68.3%.阿立哌唑片的治疗有效率为70.0%,两组疗效无显著性差异,不良反应无显著性差异(P>0.05).结论:阿立哌唑口腔崩解片与阿立哌唑片治疗精神分裂症均有良好的疗效与耐受性,两药差异不显著.     

Oxytocin enhances the inhibitory effects of diazepam in the rat central medial amygdala

Oxytocin is a neuropeptide that can reduce neophobia and improve social affiliation. In vitro, oxytocin induces a massive release of GABA from neurons in the lateral division of the central amygdala which results in inhibition of a subpopulation of peripherally projecting neurons in the medial division of the central amygdala (CeM). Common anxiolytics, such as diazepam, act as allosteric modulators of GABA(A) receptors. Because oxytocin and diazepam act on GABAergic transmission, it is possible that oxytocin can potentiate the inhibitory effects of diazepam if both exert their pre, - respectively postsynaptic effects on the same inhibitory circuit in the central amygdala. We found that in CeM neurons in which diazepam increased the inhibitory postsynaptic current (IPSC) decay time, TGOT (a specific oxytocin receptor agonist) increased IPSC frequency. Combined application of diazepam and TGOT resulted in generation of IPSCs with increased frequency, decay times as well as amplitudes. While individual saturating concentrations of TGOT and diazepam each decreased spontaneous spiking frequency of CeM neurons to similar extent, co-application of the two was still able to cause a significantly larger decrease. These findings show that oxytocin and diazepam act on different components of the same GABAergic circuit in the central amygdala and that oxytocin can facilitate diazepam effects when used in combination. This raises the possibility that neuropeptides could be clinically used in combination with currently used anxiolytic treatments to improve their therapeutic efficacy.     

Opiate effects in the amygdala central nucleus on heart rate conditioning in rabbits

Opiate agents were administered into the central nucleus of the amygdala complex of rabbits prior to either classical conditioning or pseudoconditioning of heart rate responding. Compared to control groups, opiate administration into the central nucleus did not significantly alter baseline heart rate, heart rate responding during habituation trials to presentations of the conditioned stimulus alone, or heart rate responding during the pseudoconditioning procedure. However, opiate administration altered the acquisition of a conditioned bradycardia response during classical conditioning trials in which the offset of the conditioned stimulus was coincident with the presentation of an aversive unconditioned stimulus. The opiate agonist levorphanol (5.0 nmole) significantly impaired the acquisition of the conditioned bradycardia response. This effect was observed to be stereospecific and blocked by concurrent administration of the opiate antagonist naloxone (2.5 nmole). Naloxone (2.5 nmole) administration alone significantly increased the magnitude of the conditioned bradycardia response. These effects produced by opiate administration into the central nucleus were not observed following administration of the same agents into sites 1–2 mm dorsal to the central nucleus.     

Escitalopram effects on insula and amygdala BOLD activation during emotional processing

Rationale The amygdala and insular cortex are integral to the processing of emotionally salient stimuli. We have shown in healthy volunteers that an anxiolytic agent, lorazepam, dose-dependently attenuates activation of limbic structures. Objective The current study investigated whether administration of a selective serotonin reuptake inhibitor (SSRI), escitalopram, alters the activation of limbic structures. We hypothesized that subchronic (21 days) SSRI treatment attenuates the activation of the amygdala and insula during processing of emotional faces. Materials and methods Thirteen healthy volunteers participated in a double-blind, placebo-controlled, crossover, randomized study. After 21 days of treatment with either escitalopram or placebo, participants underwent functional magnetic resonance imaging (fMRI) during which all subjects completed an emotion face assessment task, which has been shown to elicit amygdala and insula activation. Results Subjects activated the bilateral insula and amygdala after treatment with both escitalopram and placebo. In subjects who were adherent to the protocol (as evidenced by sufficiently high urine concentrations of escitalopram), a reduction in amygdala activation was seen in the escitalopram condition compared to placebo. Conclusion The current investigation provides further evidence for the mechanism of action of SSRIs through the attenuation of activation in brain regions responsible for emotion processing and provides support for the use of blood oxygenation level-dependent fMRI with pharmacological probes to help identify the specific therapeutic effect of these agents in patients with anxiety and mood disorders.     

Enkephalin analogue effects in the amygdala central nucleus on conditioned heart rate

The experiment was conducted to assess the effects of enkephalin analogue administration into the amygdala central nucleus on the acquisition of classically conditioned heart rate responding in rabbits. Bilateral injections of either D-Ala2, Met5-enkephalinamide (DALA) or D-Ala2, D-Leu5-enkephalin (DADL) were administered in a 1.0 microliter volume into the central nucleus immediately prior to the conditioning session. Administration of DALA significantly attenuated the acquisition of conditioned heart rate responding whereas groups which received comparable doses of DADL exhibited conditioned responding which did not differ from the vehicle-injected control group. The effect on conditioned responding produced by DALA administration was blocked by concurrent administration of the opiate antagonist naloxone. These results provide some support for the involvement of mu receptor activity within the central nucleus region of the amygdala in conditioning processes.     

The effects of chronic ethanol administration on amygdala neuronal firing and ethanol withdrawal seizures

Physical dependence on ethanol results in an ethanol withdrawal (ETX) syndrome including susceptibility to audiogenic seizures (AGS) in rodents after abrupt cessation of ethanol. Chronic ethanol administration and ETX induce functional changes of neurons in several brain regions, including the amygdala. Amygdala neurons are requisite elements of the neuronal network subserving AGS propagation during ETX induced by a subacute "binge" ethanol administration protocol. However, the effects of chronic ethanol administration on amygdala neuronal firing and ETX seizure behaviors are unknown. In the present study ethanol (5g/kg) was administered intragastrically in Sprague-Dawley rats once daily for 28days [chronic intermittent ethanol (CIE) protocol]. One week later the rats began receiving ethanol intragastrically three times daily for 4days (binge protocol). Microwire electrodes were implanted prior to CIE or on the day after CIE ended to record extracellular action potentials in lateral amygdala (LAMG) neurons. The first dose of ethanol administered in the binge protocol following CIE treatment did not alter LAMG neuronal firing, which contrasts with firing suppression seen previously in the binge protocol alone. These data indicate that CIE induces neuroadaptive changes in the ETX network which reduce LAMG response to ethanol. LAMG neuronal responses to acoustic stimuli prior to AGS were significantly decreased during ETX as compared to those before ethanol treatment. LAMG neurons fired tonically throughout the tonic convulsions during AGS. CIE plus binge treatment resulted in a significantly greater mean seizure duration and a significantly elevated incidence of death than was seen previously with the binge protocol alone, indicating an elevated seizure severity following chronic ethanol administration.     

立体定向颅内多靶点毁损术治疗难治性精神病

目的探讨立体定向手术治疗难治性精神病的近期疗效。方法采用螺旋CT薄层扫描解剖定位,立体定向下双侧杏仁核、扣带回、内囊前肢、隔区、尾状核下神经束等多靶点组合,射频热凝毁损治疗108例难治性精神病患者,术中采用微电极记录靶点电生理信号,结合电阻值测定验证靶点位置,进行功能定位。术后2周及1、3、6个月分别对治疗效果进行综合测评。结果108例患者中,恢复7例,显著进步81例,进步15例,无变化5例。总有效率为95.4%。无严重并发症及永久性并发症出现。术后患者疗效稳定,服用抗精神病药物剂量明显减少。结论立体定向下颅内多靶点射频热凝毁损术配合适量的药物是治疗难治性精神病的一种有效方法。     

Factors that determine the non-linear amygdala influence on hippocampus-dependent memory

Stressful experiences are known to either improve or impair hippocampal-dependent memory tasks and synaptic plasticity. These positive and negative effects of stress on the hippocampus have been largely documented, however little is known about the mechanism involved in the twofold influence of stress on hippocampal functioning and about what factors define an enhancing or inhibitory outcome. We have recently demonstrated that activation of the basolateral amygdala can produce a biphasic effect, enhancement or inhibition, of hippocampal synaptic plasticity, depending on the timing of activation (priming or spaced activation). A key question is under which conditions do the effects of amygdala activation on hippocampus dependent memory functions change from improvement to impairment of learning and memory. In this chapter we suggest that hippocampal outcome of amygdala activation may be critically dependent on four main factors: (1) The intensity of amygdala activation, (2) the temporal relation between the activation of the amygdala and the hippocampus dependent memory function, (3) the duration of amygdala activation, and (4) the contextual input during the processing of the information.     

利多卡因对电点燃模型的作用

目的研究利多卡因对电点燃模型的作用。方法采用腹腔注射的给药途径,观察杏仁核点燃大鼠的行为表现,以Racine分级作为评价标准。结果利多卡因0.5～25.0mg/kg腹腔注射可依赖性抑制大鼠杏仁核点燃作用,提高阈值,降低Rcine分级(P<0.01)。利多卡因剂量>30mg/kg,有明显的兴奋作用(P<0.05)。结论利多卡因对大鼠杏仁核点燃有兴奋和抵制双重作用。     

Differential effects of excitotoxic lesions of the amygdala on cocaine-induced conditioned locomotion and conditioned place preference

The reinforcing properties of cocaine can readily become associated with salient environmental stimuli that acquire secondary reinforcing properties. This type of classical conditioning is of considerable clinical relevance, as intense drug craving can be evoked by the presentation of stimuli previously associated with the effects of cocaine. Given the large body of evidence that implicates the amygdaloid complex in the learning of stimulus-reward associations, the present experiments examined the effects of quinolinic acid lesions of the amygdala on cocaine-induced conditional locomotion and conditioned place preference (CPP). Destruction of the amygdala did not affect basal or cocaine-induced locomotion, suggesting that the amygdala does not mediate the unconditioned psychomotor stimulant effects of this drug. Preconditioning lesions also failed to affect cocaine-induced conditional locomotion. Specifically, exposure of both lesioned and non-lesioned rats to a cocaine-paired environment produced significant conditional increases in locomotion. This lack of effect was contrasted by a complete blockade of cocaine-induced CPP by the amygdaloid lesions. These data demonstrate that cocaine-induced stimulus-reward conditioning can be differentially affected by lesions of the amygdala.     

Role of the basolateral amygdala in mediating the effects of the fatty acid amide hydrolase inhibitor URB597 on HPA axis response to stress

The endocannabinoid system is an important regulator of neuroendocrine and behavioral adaptation in stress related disorders thus representing a novel potential therapeutic target. The aim of this study was to determine the effects of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on stress mediators of HPA axis and to study the role of the basolateral amygdala (BLA) in responses to forced swim stress.Systemic administration of URB597 (0.1 and 0.3 mg/kg) reduced the forced swim stress-induced activation of HPA axis. More specifically, URB597 decreased stress-induced corticotropin-releasing hormone (CRH) mRNA expression in the paraventricular nucleus (PVN) of the hypothalamus, and pro-opiomelanocortin (POMC) mRNA expression dose-dependently in pituitary gland without affecting plasma corticosterone levels. URB597 treatment also attenuated stress-induced neuronal activation of the amygdala and PVN, and increased neuronal activation in the locus coeruleus (LC) and nucleus of solitary tract (NTS). Injection of the CB1 receptor antagonist AM251 (1 ng/side) in the BLA significantly attenuated URB597-mediated effects in the PVN and completely blocked those induced in the BLA.These results suggest that the BLA is a key structure involved in the anti-stress effects of URB597, and support the evidence that enhancement of endogenous cannabinoid signaling by inhibiting FAAH represents a potential therapeutic strategy for the management of stress-related disorders.