Endogenous opiates: 1986

This is the ninth installment of our annual review of research involving the endogenous opiate peptides. It is restricted to the non-analgesic and behavioral studies of the opiate peptides published in 1986. The specific topics this year include stress; tolerance and dependence; eating; drinking; gastrointestinal, renal, and hepatic processes; mental illness; learning, memory, and reward; cardiovascular responses; respiration and thermoregulation; seizures and other neurological disorders; activity; sex, pregnancy, and development; and some other behaviors.     

Palmar flexion creases in schizophrenia

Palmar flexion creases have been studied in schizophrenics with a family history of schizophrenia or other psychiatric disorders and without such a background, and compared to a control population. Palmar flexion creases have been analyzed according to the method suggested byBali & Chaube (1971). When compared to controls, differences in the DRBC and TRBC frequencies are significant in the subgroup with no family history, supporting the existence of biological heterogeneity in schizophrenia, and of congenital factors when there is no known genetic background.     

Excitatory Amino Acid Receptors in the Ventral Tegmental Area Regulate Dopamine Release in the Ventral Striatum

Abstract: The role of excitatory amino acid (EAA) receptors located in the ventral tegmental area (VTA) in tonic and phasic regulation of dopamine release in the ventral striatum was investigated. Microdialysis in conscious rats was used to assess dopamine release primarily from the nucleus accumbens shell region of the ventral striatum while applying EAA antagonists or agonists to the VTA. Infusion of the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (25 and 100 µ M ) into the VTA did not affect dopamine release in the ventral striatum. In contrast, intra-VTA infusion of the NMDA receptor antagonist 2-amino-5-phosphopentanoic acid (100 and 500 µ M ) dose-dependently decreased the striatal release of dopamine. Intra-VTA application of the ionotropic EAA receptor agonists NMDA and AMPA dose-dependently (10 and 100 µ M ) increased dopamine efflux in the ventral striatum. However, infusion of 50 or 500 µ M trans -(±)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD), a metabotropic EAA receptor agonist, did not significantly affect these levels. These data suggest that NMDA receptors in the VTA exert a tonic excitatory influence on dopamine release in the ventral striatum. Furthermore, dopamine neurotransmission in this region may be enhanced by activation of NMDA and AMPA receptors, but not ACPD-sensitive metabotropic receptors, located in the VTA. These data further suggest that EAA regulation of dopamine release primarily occurs in the VTA as opposed to presynaptically at the terminal level.     

大脑皮层信息传输和精神分裂症

本工作用脑电图为测试手段,比较了正常人与精神分裂症病人的大脑皮层的信息传输。我们发现精神分裂病人的大脑皮层信息传输有非常特殊的现象。正常人在睁眼时大脑皮层信息传输比较活跃,当闭眼时信息传输相对减少。而精神分裂症病人则恰好相反。闭眼时信息传输很活跃而睁眼对它们产生抑制,严重的情况可与正常人深度睡眠时类似。经过近三百多例的统计分析这种差别是非常显著的。我们认为这种方法可能作为诊断精神分裂症的客观指标。     

Dopamine D4-Like Receptor Elevation in Schizophrenia: Cloned D2 and D4 Receptors Cannot Be Discriminated by Raclopride Competition Against [3H]Nemonapride

Abstract: Three independent studies have found that the density of dopamine D4-like receptors is elevated in postmortem brain striata in schizophrenia. This elevation has been questioned by a fourth study that used a different method and failed to detect a biphasic component when raclopride was used to compete against the binding of 1 n M [³H]nemonapride to schizophrenia tissue. To test whether this competition method could distinguish between dopamine D2 and D4 receptors, the present study used mixtures of only these two cloned receptors, free of all other receptors. Using combinations of cloned dopamine D2 and D4 receptors, this competition method could not resolve these components up to a level of 48% D4 receptors. Thus, the objections raised by the findings of the fourth study, mentioned above, do not appear valid. Furthermore, the present results indicate that the data using such a competition method actually mask a manyfold marked elevation in the density of dopamine D4-like receptors in schizophrenia.     

Demonstration of high opioid-like activity in isolated peptides from wheat gluten hydrolysates

Because of a possible relationship between schizophrenia and celiac disease, a condition in some individuals who are sensitive to wheat gluten proteins in the diet, there has been interest in observations that peptides derived from wheat gluten proteins exhibit opioid-like activity in in vitro tests. To determine the origin of the peptides exhibiting opioid activity, wheat proteins were fractionated by size (gel filtration), by charge differences (ion exchange chromatography) and by differences in hydrophobicity (reversed-phase HPLC). These fractions were hydrolyzed by pepsin or pepsin and trypsin and the resulting peptides separated by gel filtration chromatography. The separated peptides were tested for opioid-like activity by competitive binding to opioid receptor sites in rat brain tissue in the presence of tritium-labeled dihydromorphine. The peptides showed considerable differences in activity; while some peptides exhibited no activity, 0.5 mg of the most active peptides were equivalent to 1 nM of morphine in the binding assay. The most active peptides were derived from the gliadin fraction of the gluten complex.     

Endogenous opiates: 1979

Since the discovery in 1971 of opiate receptors and later of the opiate-like peptides, there has been widespread interest in determining their exact localization, number and kinds, nature, and physiological and pharmacological functions. Between 1971 and 1978, vast amounts of research investigated these problem areas, but in 1979 alone the literature on the opiate peptides nearly doubled. This review is the second of an annual series and summarizes the highlights of the work published during 1979.     

Endogenous opiates: 1980

Vast amounts of research have been done that have attempted to delineate the pharmacological and physiological effects of the endogenous opiate peptides. A great deal of knowledge has also been accumulated in a limited time span concerning the types and locations of the opiate receptors and peptides, as well as their functions. In 1980, reports were made concerning the effects of these peptides on analgesia, on tolerance and dependence, on activity, on learning and memory, on schizophrenia and other types of emotional disturbances, and on physiological responses such as eating and drinking, cardiovascular responses, and sexual function. Additional understanding was also gained concerning their interactions with neurotransmitters, other neuropeptides, and hormones. These and other studies published only in 1980 are reviewed in this paper, which is the third of an annual series.     

血清DCN、NRG-1、MIF水平与首发未服药精神分裂症患者临床症状和认知功能的相关性分析

目的:探讨血清核心蛋白多糖(DCN)、神经调节蛋白-1(NRG-1)、巨噬细胞迁移抑制因子(MIF)水平与首发未服药精神分裂症患者临床症状和认知功能的相关性。方法:选择2018年1月~2020年11月期间长江大学附属第一医院收治的首发未服药精神分裂症患者80例作为精神分裂症组,同期于长江大学附属第一医院进行体检的健康志愿者80例作为对照组。应用阳性和阴性症状量表(PANSS)评估患者精神病理症状,应用MATRICS共识认知成套测验(MCCB)评估所有受试者认知功能。根据PANSS评分将精神分裂症组分为PANSS评分高分组和低分组,比较两组血清DCN、NRG-1、MIF水平,并分析以上指标水平与PANSS总分、MCCB各项评分的相关性。结果:精神分裂症组患者PANSS总分为(77.18±13.57)分。精神分裂症组MCCB各项评分均低于对照组(P<0.05)。精神分裂症组血清DCN、NRG-1水平低于对照组,MIF水平高于对照组(P<0.05)。PANSS高分组血清DCN、NRG-1水平低于PANSS低分组,MIF水平高于PANSS低分组(P<0.05)。Pearson相关性分析显示,首发未服药精神分裂症患者血清DCN、NRG-1水平与PANSS总分呈负相关,与MCCB各项评分呈正相关,MIF水平与PANSS总分呈正相关,与MCCB各项评分呈负相关(均P<0.05)。结论:首发未服药精神分裂症患者血清DCN、NRG-1、MIF水平异常,且以上指标水平与患者临床症状和认知功能受损有一定联系,提示检测以上指标水平可能为该病患者认知功能及临床症状的评估提供参考。     

Reduced striatal ecto-nucleotidase activity in schizophrenia patients supports the “adenosine hypothesis”

Schizophrenia (SZ) is a major chronic neuropsychiatric disorder characterized by a hyperdopaminergic state. The hypoadenosinergic hypothesis proposes that reduced extracellular adenosine levels contribute to dopamine D₂ receptor hyperactivity. ATP, through the action of ecto-nucleotidases, constitutes a main source of extracellular adenosine. In the present study, we examined the activity of ecto-nucleotidases (NTPDases, ecto-5′-nucleotidase, and alkaline phosphatase) in the postmortem putamen of SZ patients (n = 13) compared with aged-matched controls (n = 10). We firstly demonstrated, by means of artificial postmortem delay experiments, that ecto-nucleotidase activity in human brains was stable up to 24 h, indicating the reliability of this tissue for these enzyme determinations. Remarkably, NTPDase-attributable activity (both ATPase and ADPase) was found to be reduced in SZ patients, while ecto-5′-nucleotidase and alkaline phosphatase activity remained unchanged. In the present study, we also describe the localization of these ecto-enzymes in human putamen control samples, showing differential expression in blood vessels, neurons, and glial cells. In conclusion, reduced striatal NTPDase activity may contribute to the pathophysiology of SZ, and it represents a potential mechanism of adenosine signalling impairment in this illness.