近交系小海马结构兴奋性氨基酸受体密度的变化

应用定量放射自显影技术，以氚标配体ＭＫ－８０１、ＡＭＰＡ和ＫＡ分别标记ＮＭＤＡ、ＡＭＰＡ和ＫＡ受体，定量观察了七种近交系小鼠海马结构内兴奋性氨基酸受体的区域分布类型和受体密度变化。结果表明，海马ＣＡ１区含有高密度ＮＭＤＡ和ＡＭＡＰ受体，ＣＡ３和齿状回含高密度ＫＡ受体。三种受体在海马各区的分布类型无明显系间差异，而其受体密度存在着明显的系间差别。ＮＭＤＡ和ＡＭＡＰ受体在ＢＡＬＢ／ｃ鼠海马显示最高密度     

KA1表达再分布对神经元兴奋毒性的影响****

背景：特异的兴奋性神经递质受体过度活化时便发生细胞的兴奋性中毒,有关NMDA受体和AMPA受体活化致细胞兴奋性中毒死亡通路较为明确,但关于红藻氨酸(Kainate,KA)受体的功能到目前为止仍未明了。 目的：探究小鼠海马内注射KA之后KA1受体的再分布状况对中枢神经元兴奋性中毒的影响。 方法：成年雄性C57BL6小鼠海马内注射KA或PBS,2 h后进行Bederson体征评分、全脑切片免疫组化分析和死亡神经元检测。 结果与结论：海马内注射KA 2 h后,Bederson体征评分表明中枢神经功能出现明显损伤;KA1受体表达的变化主要出现在海马CA1和CA3区,在CA1区的表达上调明显,并开始出现神经元死亡,4~6 h后可见大量神经元死亡。结果表明 KA促使KA1受体亚单位在海马神经元CA区重新分布,增加神经元对兴奋性氨基酸毒性的敏感性,导致神经细胞死亡,中枢神经功能缺失。     

NMDA受体在突触调控中的作用

中枢神经系统内含有丰富的作为重要神经递质的兴奋性氨基酸,因此也广泛存在兴奋性氨基酸受体,突触后膜的兴奋性氨基酸受体与相应神经递质（谷氨酸、天冬氨酸等）结合后产生兴奋性突触后电位（EPSP）而实现其生理效应。兴奋性氨基酸受体分为离子型和代谢型两类,根据对不同激动剂的选择性和反应强度,离子型受体分为NMDA受体、使君子酸（AMPA）受体和海人藻酸（KA）受体三种类型。     

N-甲基-D-天冬氨酸受体-3亚基研究进展

<正>NMDA受体(N-methyl-D-aspartate receptor,NMDAR)是一种离子通道型谷氨酸受体,这类受体还包括KA受体(kainic acid receptor,KAR)和AMPA受体(α-amino-3-hydrox-y-5-methyl-4-isoxa-zolep-propionate receptor,AMPAR)。绝大部分NMDA受体分布于中枢神经系统,参与兴奋性突触传     

AMPA和KA受体的药理学和生理功能

谷氨酸受体是脊椎动物中枢神经系统中一类主要的兴奋性神经递质受体，可分为离子型和代谢型两大类。离子型谷氨酸受体（iGluR）是非特异性阳离子通道，包括NMDA、AMPA和海人藻酸（kainate，KA）受体通道（图1），它们在快速兴奋性突触传送中发挥着重要作用。由于NMDA和代谢型谷     

红藻氨酸诱导内质网应激模型的途径

背景:前期研究表明,海马内注射红藻氨酸海可诱发兴奋性红藻氨酸受体KA1亚受体在海马神经元的表达明显上调,内质网应激标志物磷酸化真核翻译起始因子2α表达增加并伴随细胞死亡。目的:探讨红藻氨酸海马内注射后内质网应激发生的机制。方法:取昆明小鼠32只,将0.15 nmol红藻氨酸注入海马CA1区域,注射时间为60 s。分别于红藻氨酸注射后第1,2,3,4,5,6,8,12小时灌注取脑,灌注取脑前进行Bederson体征评分,然后行全脑切片FJB染色分析与免疫荧光双标记观察。结果与结论:1红藻氨酸注射后第3,4,5,6,8小时,Bederson体征评分表明中枢神经功能出现明显损伤,FJB染色示小鼠海马内神经元死亡明显;注射后第1,2,12小时,Bederson体征评分中枢神经功能未见明显损伤,FJB染色小鼠海马神经元死亡结果不明显。2根据FJB结果,取第3,8小时的脑片做免疫组化。海马内注射红藻氨酸后导致海马神经元中KA1和磷酸化真核翻译起始因子2α在相同的时间点表达明显上调,将KA1与磷酸化真核翻译起始因子2α图片结果进行叠加处理,两者完全重合,表明KA1的表达和内质网应激发生在同一个神经细胞内。结果表明红藻氨酸首先诱导了兴奋性膜上受体KA1表达的上调,其KA1的表达上调可能引起细胞内质网功能紊乱,导致内质网应激反应,并进一步促进了神经细胞的死亡。     

快速老化小鼠海马突触体内NMDA受体的表达变化

目的:观察NMDA受体在SAMP8小鼠海马突触体内的表达变化。方法:首先应用生物化学的方法分离海马突触蛋白,并对其进行鉴定。其次,Western Blot检测NMDA受体的主要亚基NR1、NR2A和NR2B在SAMP8小鼠海马突触体内的表达变化。结果:PSD-95和synaptophysin特异性抗体检测显示突触蛋白的分离是成功的。SAMP8小鼠海马内NR1、NR2A和NR2B在突触的表达均显著低于SAMR1小鼠。进一步分析NR1、NR2A和NR2B蛋白在突触的表达量占总表达量的比值,SAMP8小鼠同样显著低于SAMR1小鼠,而SAMR1和CD-1小鼠间没有显著性差异。结论:SAMP8小鼠海马突触体内NR1、NR2A和NR2B的蛋白表达水平均显著性降低,推测NMDA受体在突触表达水平的降低可能是导致受体功能失调,激发突触功能损伤信号途径的原因之一,进而导致SAMP8小鼠学习记忆功能的下降。     

快速老化小鼠P8海马神经元突触可塑性相关的AMPA受体表达异常

目的比较快速老化小鼠P8(SAMP8)与抗快速老化小鼠R1(SAMR1)海马神经元突触可塑性相关的谷氨酸α-氨基-3-羟基-5-甲基-4-异唑丙酸(AMPA)受体表达差异,为阿尔兹海默病(AD)的发病机制提供实验依据。方法取雄性10月龄SAMP8 10只和SAMR1 9只,应用Morris水迷宫实验评价动物学习记忆能力,透射电子显微镜观察海马CA1区神经元突触界面超微结构,蛋白质免疫印迹法检测海马AMPA受体亚基GluR1、GluR2的表达。结果与SAMR1比较,SAMP8逃避潜伏期延长,目标象限时间百分比下降,穿台次数减少;海马CA1区神经元突触后致密带变薄,突触间隙增宽,突触界面曲率下降;海马GluR2含量下降,GluR1含量有下降趋势,但差异无统计学意义。结论海马AMPA受体异常可能是导致突触可塑性受损,引发SAMP8认知障碍的原因之一,AMPA受体在AD的发病中可能占有重要地位。     

红藻氨酸对大鼠海马锥体细胞钙电流的影响

目的：应用膜片钳技术,观察红藻氨酸（KA）对大鼠海马锥体细胞ca2＋电流的影响,以研究癫痫的发病机制。方法：采用酶加机械分离法制备出生10～12d的大鼠海马锥体神经元标本,用全细胞膜片钳技术测定其生理学特性及观察KA对ca2＋电流的影响。结果：分离出的海马锥体细胞形态正常,有较长突起;用膜片钳技术证实,其保存了主要的离子通道活性。KA20μmol／L和100μmol／L的浓度均可使海马锥体细胞ca2＋电流峰值增大（n=8,P〈0．01）。结论：①大鼠海马锥体神经细胞具有明显的突起,细胞膜表面光洁、晕光好,适用于膜片钳实验研究;②KA使ca2＋内流增加,引起“Ca”超载”导致细胞毒性等一系列反应;③KA通过激活α-氨基羟甲基恶唑丙酸（AMPA）受体,诱发快速的兴奋性突触后电位（EPSP）,参与兴奋性突触传递。AMPA受体的激活可能是癫痫的发病机制之一。     

兴奋性氨基酸受体的分子生物学

兴奋性氨基酸(EAA)受体有5种类型。如同 GABA、5-HT 和胆碱能受体等一样,EAA受体亦可分为两大类。其中 NMDA 和非 NMDA 受体都具有4个跨膜区段(TM),并由 TM 的某些顺序组成了离子通道:促代谢受体(mGluR)则系具有7个 TM、与 G 蛋白相偶联的受体,它是通过促进磷脂酰肌醇分解,产生第二信使而发挥作用的。NMDA、非 NMDA 和促代谢受体激活均为突触传递的长时程增强(LTP)所必需,后者乃是记忆形成和维持的必要条件。     

Differential expression of NMDA and AMPA receptor subunits in rat dorsal and ventral hippocampus

Several studies have demonstrated anatomical and functional segregation along the dorsoventral axis of the hippocampus. This study examined the possible differences in the AMPA and NMDA receptor subunit composition and receptor binding parameters between dorsal and ventral hippocampus, since several evidence suggest diversification of NMDA receptor-dependent processes between the two hippocampal poles. Three sets of rat dorsal and ventral hippocampus slices were prepared: 1) transverse slices for examining a) the expression of the AMPA (GluRA, GluRB, GluRC) and NMDA (NR1, NR2A, NR2B) subunits mRNA using in situ hybridization, b) the protein expression of NR2A and NR2B subunits using Western blotting, and c) by using quantitative autoradiography, c(1)) the specific binding of the AMPA receptor agonist [(3)H]AMPA and c(2)) the specific binding of the NMDA receptor antagonist [(3)H]MK-801, 2) longitudinal slices containing only the cornus ammonis 1 (CA1) region for performing [(3)H]MK-801 saturation experiments and 3) transverse slices for electrophysiological measures of NMDA receptor-mediated excitatory postsynaptic potentials. Ventral compared with dorsal hippocampus showed for NMDA receptors: 1) lower levels of mRNA and protein expression for NR2A and NR2B subunits in CA1 with the ratio of NR2A /NR2B differing between the two poles and 2) lower levels of [(3)H]MK-801 binding in the ventral hippocampus, with the lowest value observed in CA1, apparently resulting from a decreased receptor density since the B(max) value was lower in ventral hippocampus. For the AMPA receptors CA1 our results showed in ventral hippocampus compared with dorsal hippocampus: 1) lower levels of mRNA expression for GluRA, GluRB and GluRC subunits, which were more pronounced in CA1 and in dentate gyrus region and 2) lower levels of [(3)H]AMPA binding. Intracellular recordings obtained from pyramidal neurons in CA1 showed longer NMDA receptor-mediated excitatory postsynaptic potentials in ventral hippocampus compared with dorsal hippocampus. In conclusion, the differences in the subunit mRNA and protein expression of NMDA and AMPA receptors as well as the lower density of their binding sites observed in ventral hippocampus compared with dorsal hippocampus suggest that the glutamatergic function differs between the two hippocampal poles. Consistently, the lower value of the ratio NR2A/NR2B seen in the ventral part would imply that the ventral hippocampus NMDA receptor subtype is functionally different than the dorsal hippocampus subtype, as supported by our intracellular recordings. This could be related to the lower ability of ventral hippocampus for long-term synaptic plasticity and to the higher involvement of the NMDA receptors in the epileptiform discharges, observed in ventral hippocampus compared with dorsal hippocampus.     

Rapid cortico-limbic alterations in AMPA receptor densities after administration of PCP: implications for schizophrenia

Phencyclidine (PCP), a non-competitive NMDA/glutamate receptor antagonist, is a psychotomimetic drug that produces a syndrome in normal humans that resembles schizophrenia. The present study investigated the mechanisms of PCP actions by examining the density of glutamate and muscarinic receptors in the rat brain 4h after a single injection of PCP. We used receptor autoradiography and [3H]MK801, [3H]AMPA, [3H]pirenzepine and [3H]AFDX384 to target glutamate NMDA, glutamate AMPA and muscarinic M1 and M2 receptors, respectively. The major outcome from the present study was an overall decrease in levels of the glutamate AMPA receptor density (F=14.5, d.f.=1, p<0.001) in the PCP treated rats. More specifically, PCP-treated animals displayed decreased AMPA receptor density in hippocampus CA1 (-16%), hippocampus CA2 (-25%), dentate gyrus (-27%), parietal cortex layers III-VI (-19%), central nucleus of the amygdala (-40%), and basolateral amygdala (-19%). Other brain regions examined were unaffected. PCP administration did not significantly affect glutamate NMDA, muscarinic M1 and M2 receptor density. The present study demonstrates the limbic system as the anatomical locus of alterations in AMPA receptor density after acute administration of PCP and may have implications for models of schizophrenia that focus on glutamatergic dysfunction in limbic cortical regions.     

Transient postnatal increases in excitatory amino acid binding sites in rat ventral mesencephalon.

The developmental profile of three sub-types of excitatory amino acid (EAA) binding sites was determined in the ventral mesencephalon and the striatum of rats from prenatal day 19 to adult (3 months) using membrane binding assays. In the ventral mesencephalon, there was a transient increase of EAA receptor binding sites beyond adult levels, which peaked at postnatal day 7 (P7) for [3H]glutamate binding to NMDA receptors and at P14 for [3H]AMPA and [3H]kainate binding. In the striatum, [3H]glutamate/NMDA and [3H]kainate binding reached adult levels during the early postnatal period, stabilizing at this level with no transient overexpression beyond adult levels. [3H]AMPA binding also showed an increase above adult levels at P14 in the striatum. These results raise the possibility that the transient overexpression of EAA receptors in the ventral mesencephalon may affect the developmental fate of dopaminergic and other neurons in this region.     

Ionotropic glutamate and GABA receptors in human epileptic neocortical tissue: quantitative in vitro receptor autoradiography

Since a disturbed balance between excitatory and inhibitory amino acid receptors is suggested to be an important condition for epileptogenic cortical activity, the present study has focused on the analysis of the densities of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), N-methyl-D-aspartate, kainate and GABA subtype A receptors in neocortical tissue surgically removed from patients with focal epilepsy. The mean densities (collapsed over cortical layers I-VI) and the laminar distribution patterns of [3H]AMPA, [3H]MK-801, [3H]kainate and [3H]muscimol binding to AMPA, N-methyl-D-aspartate, kainate and GABAA receptors were determined with quantitative receptor autoradiography in the neocortex of patients with focal epilepsy and controls. The tissue probes used in the present study were functionally characterized by parallel electrophysiological investigations. From that, the different probes could be subdivided into a spontaneously spiking and a non-spontaneously spiking group. The mean density of [3H]AMPA binding sites was significantly increased (+37%) in the group of epileptic brains (n = 10) compared with controls (n = 10), but the mean densities of [3H]MK-801, [3H]kainate and [3H]muscimol binding sites were not significantly altered (-8%, +/-0% and -7%, respectively). The relation between the densities of all four binding sites were simultaneously displayed as polar plots in each single brain ("receptor fingerprints"). The consistent up-regulation of [3H]AMPA binding sites in all epileptic brains was found to be associated with a down-regulation of the N-methyl-D-aspartate receptor in four of the five non-spontaneously spiking cases, and an associated up-regulation of the N-methyl-D-aspartate receptor was seen in all spontaneously spiking cases. Finally, the laminar distribution of binding site densities was analysed, since the mean densities collapsed over all neocortical layers may obscure layer-specific alterations. Layer- and receptor- specific up- or down-regulations were found in epileptic tissue compared with controls. Moreover, the laminar distribution pattern of current sinks associated with epileptiform potentials in a spontaneously spiking cortical slice was found to be co-localized with local maxima of AMPA receptor densities. The present analysis of four ionotropic glutamate and GABA receptor subtypes demonstrates a consistent and significant up-regulation of [3H]AMPA binding sites in all cases of human focal epilepsy, which co-localizes with the occurrence of sinks in current-source-density analysis. The receptor fingerprint analysis suggests a subdivision of focal epilepsy into two subtypes on the basis of neurochemical/functional correlations: (i) a spontaneously spiking subtype with increased N-methyl-D-aspartate receptor density, and (ii) a non-spontaneously spiking subtype with decreased N-methyl-D-aspartate receptor density.     

Kainate and quisqualate receptor autoradiography in rat brain after angular bundle kindling

The kainate and quisqualate types of excitatory amino acid receptor were visualized autoradiographically in brain sections from rats kindled by stimulating the angular bundle. Kainate receptors were labeled with [3H]kainate and quisqualate receptors with L-[3H]glutamate. When assayed one day after the last evoked seizure, kainate receptor binding had declined by 24-29% in stratum lucidum of hippocampal area CA3 and by 12-14% in the inner third of the dentate molecular layer, but was unchanged in the neocortex and basolateral amygdala. Saturation binding curves revealed that, under the conditions of these experiments, [3H]kainate labeled a single class of binding sites with a KD of 33-36 nM. In stratum lucidum of area CA3, kindling reduced the density of kainate receptors without altering their affinity for kainate. At the same time, quisqualate receptor binding had declined by 20-35% in many layers of the hippocampal formation and neocortex, but remained unchanged in the basolateral amygdala. Repeated stimulation or repeated seizures were required to produce these effects, since both kainate and quisqualate receptor binding were unchanged one day after a single afterdischarge. These receptor changes largely or completely reversed during a 28-day period without further stimulation. Thus maintenance of the kindled state probably cannot be explained by a long-lasting change in the expression of kainate or quisqualate receptors. The transient, regionally-selective down-regulation of these receptors may represent a compensatory response of forebrain neurons to repeated stimulation or seizures.     

Septotemporal distribution of [3H]MK-801, [3H]AMPA and [3H]Kainate binding sites in the rat hippocampus

The distribution of glutamate receptors in transverse hippocampal sections has been well investigated. However, in spite of the known septotemporal gradients of hippocampal connectivity no systematic studies exist about the distribution of glutamate receptors along the septotemporal (longitudinal) hippocampal axis. Therefore, in the present study this issue was investigated using receptor autoradiography for the [³H]MK-801, [³H]AMPA and [³H]Kainate binding sites. Hippocampi from 30-day-old rats were sectioned perpendicularly to their longitudinal axis, yielding a total of 25–30 equidistantly spaced autoradiographs for each hippocampus. For each section layer-specific concentrations of binding sites were calculated by the aid of a computerized image analysing system. The dependency of concentrations of binding sites on the septotemporal position was evaluated by regression analysis. Gradients of binding were confined to distinct hippocampal layers. Significant septotemporal gradients of [³H]MK-801 binding were observed in selected layers of CA1 and the dentate gyrus, a septal to temporal decrease of binding in the oriens and radiatum layers of CA1 being most prominent. For [³H]AMPA, significant septotemporal gradients of binding were restricted to layers of CA3, CA4 and the dentate gyrus, with values generally increasing from septal to temporal levels. The observed septotemporal gradients possibly reflect functional segregations along the longitudinal hippocampal axis and could be important for the comparability of ligand binding studies using transverse hippocampal sections or hippocampal slice cultures.     

Excitatory amino acid receptors in the human cerebral cortex: a quantitative autoradiographic study comparing the distributions of [3H]TCP, [3H]glycine, L-[3H]glutamate, [3H]AMPA and [3H]kainic acid binding sites

The excitatory amino acids are probably the major neurotransmitters in the cerebral cortex, and they act through at least three receptors: the N-methyl-D-aspartate, the quisqualate and the kainic acid receptors. Under the appropriate conditions, [3H]1-(1-(2-thienyl)-cyclohexyl)piperidine [( 3H]TCP), [3H]glycine and L-[3H]glutamate label different sites on the N-methyl-D-aspartate receptor, [3H]-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid [( 3H]AMPA) labels the quisqualate receptor and [3H]kainic acid the kainic acid receptor. The anatomical localizations of these binding sites were studied in sections of blocks removed from the cerebral cortices of eight post-mortem human brains. The results showed that, in the human cerebral cortex, [3H]TCP, [3H]glycine and L-[3H]glutamate binding sites had congruent distributions, with [3H]AMPA binding sites showing a similar distribution. In the hippocampus, these four ligands had high binding site densities in the CA1 region and the dentate gyrus molecular layer. With the exception of the striate cortex, in the neocortex, a tri-laminar pattern was seen consisting of a high density across laminae I-III, a layer of low density corresponding to the region of lamina IV, and a band of moderate density across laminae V and VI, except for [3H]AMPA where the middle zone of low density was usually wider. [3H]Kainic acid showed a binding pattern which was generally complementary to that of the other four ligands. There were low levels of [3H]kainic acid binding sites in the CA1 region of the hippocampus with higher levels in the CA3 region, the hilus, and the inner third of the dentate gyrus molecular layer. In the neocortex there was a band of high density corresponding to laminae V and VI, with a thin band of moderate binding corresponding to lamina I and the outer region of lamina II. An exception was the motor cortex where the highest level of [3H]kainic acid binding was in laminae I and II. The high degree of congruence between the binding patterns of [3H]TCP, [3H]glycine and L-[3H]glutamate (using conditions appropriate for the N-methyl-D-aspartate receptor) supports data indicating that these ligands bind to different regions of the same receptor complex. The similar distribution of [3H]AMPA binding sites, with the exception of the striate cortex, supports observations made in rodents that N-methyl-D-aspartate receptors and quisqualate receptors have similar distributions and perform different but related functions in excitatory transmission.(ABSTRACT TRUNCATED AT 400 WORDS)     

Taurine-transporter gene knockout-induced changes in GABA(A), kainate and AMPA but not NMDA receptor binding in mouse brain

The aim of this study was to determine whether the knockout of the taurine-transporter gene in the mouse affects the densities of GABA_A, kainate, AMPA and NMDA receptors in the brain. The caudate-putamen, the hippocampus and its subregions, and the cerebellum of six homozygous taurine-transporter gene knockout mice and six wild-type (WT) animals were examined by means of quantitative receptor autoradiography. Saturation studies were carried out for all four receptor types in order to find possible intergroup differences in B _max and K _D values. Taurine-transporter gene knockout animals showed significantly higher GABA_A receptor densities in the molecular layer of the hippocampal dentate gyrus and in the cerebellum than did WT animals. The densities of kainate receptors were significantly higher in the caudate-putamen, the CA1 and hilus regions of the hippocampus and in the cerebellum of knockout animals. The caudate-putamen and cerebellum of these mice also contained significantly higher AMPA receptor densities. However, there were no significant differences between knockout and WT animals concerning the densities of NMDA receptors. Reduced brain taurine levels are associated with increased GABA_A, kainate and AMPA receptor densities in some of the regions we examined.     

Septotemporal distribution of [3H]MK-801, [3H]AMPA and [3H]Kainate binding sites in the rat hippocampus

 The distribution of glutamate receptors in transverse hippocampal sections has been well investigated. However, in spite of the known septotemporal gradients of hippocampal connectivity no systematic studies exist about the distribution of glutamate receptors along the septotemporal (longitudinal) hippocampal axis. Therefore, in the present study this issue was investigated using receptor autoradiography for the [³H]MK-801, [³H]AMPA and [³H]Kainate binding sites. Hippocampi from 30-day-old rats were sectioned perpendicularly to their longitudinal axis, yielding a total of 25–30 equidistantly spaced autoradiographs for each hippocampus. For each section layer-specific concentrations of binding sites were calculated by the aid of a computerized image analysing system. The dependency of concentrations of binding sites on the septotemporal position was evaluated by regression analysis. Gradients of binding were confined to distinct hippocampal layers. Significant septotemporal gradients of [³H]MK-801 binding were observed in selected layers of CA1 and the dentate gyrus, a septal to temporal decrease of binding in the oriens and radiatum layers of CA1 being most prominent. For [³H]AMPA, significant septotemporal gradients of binding were restricted to layers of CA3, CA4 and the dentate gyrus, with values generally increasing from septal to temporal levels. The observed septotemporal gradients possibly reflect functional segregations along the longitudinal hippocampal axis and could be important for the comparability of ligand binding studies using transverse hippocampal sections or hippocampal slice cultures. Accepted: 2 April 1998     

Loss of hippocampal [3H]TCP binding in Alzheimer's disease

We have previously demonstrated a marked loss in N-methyl-D-aspartate (NMDA) receptors in the hippocampus and cerebral cortex of patients dying with dementia of the Alzheimer type (DAT). In addition, we have found that the dissociative anesthetic N-(1-[2-thienyl]cyclohexyl)3,4-piperidine ([3H]TCP) binds to a site whose regional distribution is highly correlated with that of NMDA receptor sites. We studied the binding of [3H]TCP to sections of hippocampi from 8 controls, 12 patients with DAT and 7 patients with other dementias. [3H]TCP binding was significantly reduced in strata pyramidalia of CA1/CA2, CA3 and subiculum of DAT hippocampal formation compared to that of control. Labelled dissociative anesthetics could potentially be used with positron emission tomography in the diagnosis of DAT.