Critical reviews in neurobiology最新文献

{"title":"Changes in apparent rates of receptor binding in the intact brain in relation to the heterogeneity of reaction environments.","authors":"O Inoue,&nbsp;K Kobayashi,&nbsp;A Gee","doi":"10.1615/critrevneurobiol.v13.i2.40","DOIUrl":"https://doi.org/10.1615/critrevneurobiol.v13.i2.40","url":null,"abstract":"<p><p>Neuroreceptor imaging by PET or SPECT has been widely applied in the field of neurobiology, from basic to clinical investigations, and has the potential to reveal the neurochemical basis of various neurological and psychiatric diseases as well as to provide new knowledge in the field of neuropharmacology. In contrast to the static nature of in vitro systems, neurotransmission systems in the intact brain constitute part of a dynamic and communicating environment. Thus, it is important to develop new functional imaging methods that reflect neural communications and the dynamism of signal transmission in the living brain. In vivo receptor binding can be altered not only by competitive inhibition by endogenous neurotransmitters but by trans-synaptic effects, and investigation of neural interactions by detection of changes in receptor binding therefore presents a potential method for studying this phenomenon. Recently, several PET studies on in vivo neural interactions using the D2 receptor ligand [11C]-raclopride concluded that the phenomenon was mediated by changes in synaptic endogenous dopamine concentrations that compete with [11C]-raclopride binding for neuroreceptor occupancy. However, a growing body of evidence indicates that these changes in in vivo receptor binding cannot be fully explained by competitive inhibition by endogenous ligand, and alternative mechanisms for the interneuronal modulation of receptor binding are addressed. This review highlights some of the discrepancies observed between in vitro and in vivo receptor binding studies with respect to a number of phenomena, including the heterogeneity of the reaction field surrounding receptors. Quantitative receptor binding studies are usually analyzed by using 'static' binding parameters, such as the Bmax, and KD, which are normally determined by in vitro assays. In addition to these parameters, the apparent association and dissociation rate constants (kon, koff) play equally significant roles in receptor binding in the intact brain is expected. The concepts of \"diffusion boundary\" and \"reaction volume\" are introduced, and discussions on some of the discrepancies between in vivo and in vitro receptor binding phenomena are presented.</p>","PeriodicalId":10778,"journal":{"name":"Critical reviews in neurobiology","volume":"13 2","pages":"199-225"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21374679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain imaging studies of cocaine abuse: implications for medication development.","authors":"E D London,&nbsp;K R Bonson,&nbsp;M Ernst,&nbsp;S Grant","doi":"10.1615/critrevneurobiol.v13.i3.10","DOIUrl":"https://doi.org/10.1615/critrevneurobiol.v13.i3.10","url":null,"abstract":"<p><p>Contemporary in vivo brain imaging techniques confer the ability to assess brain function and structure noninvasively, and thereby can yield information to help guide the development of new treatments for substance abuse. The advantages and limitations of the major imaging modalities (positron emission tomography [PET], single photon emission computed tomography [SPECT], structural and functional magnetic resonance imaging [MRI, fMRI, respectively]) are discussed with respect to their applicability to research on cocaine abuse. The effects of acute administration of cocaine have been studied using PET and fMRI, with PET manifesting decreases in cerebral glucose metabolism and blood flow, and fMRI revealing regional effects that are correlated temporally with subjective responses. In addition, studies of drug abusers, abstinent from cocaine for various lengths of time, have revealed persistent differences in brain function and structure, especially in the frontal cortex, when compared with parameters in the brains of subjects who do not use illicit drugs of abuse. PET studies also have revealed abnormalities in markers for dopaminergic and opioid systems during withdrawal from cocaine. Moreover, studies of cue-elicited craving for cocaine demonstrate a connection between the response to drug-related stimuli and neural elements of cognition and emotion. The future directions of in vivo brain imaging to identify functional and structural alterations in the brains of cocaine abusers are discussed in relation to the development of medications to treat cocaine dependence.</p>","PeriodicalId":10778,"journal":{"name":"Critical reviews in neurobiology","volume":"13 3","pages":"227-42"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21650509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring brain chemistry in vivo: voltammetric techniques, sensors, and behavioral applications.","authors":"R D O'Neill,&nbsp;J P Lowry,&nbsp;M Mas","doi":"10.1615/critrevneurobiol.v12.i1-2.40","DOIUrl":"https://doi.org/10.1615/critrevneurobiol.v12.i1-2.40","url":null,"abstract":"<p><p>Clinical intervention in neurological disorders is almost invariably achieved using chemical agents that act on neuromediator-related sites, suggesting that intercellular chemical signaling plays a major role in determining the properties of neural networks. A variety of microvoltammetric sensors and techniques have been developed over the last 25 years to study neuromediators in intact brain in vivo, and in isolated tissues, for animal models of behavior and disease. This review, with over 600 citations, considers the advantages and limitations of the different approaches, including progress in biosensor design, illustrated by studies on the neurochemical bases of a wide variety of behaviors.</p>","PeriodicalId":10778,"journal":{"name":"Critical reviews in neurobiology","volume":"12 1-2","pages":"69-127"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20373878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Felbamate: clinical and molecular aspects of a unique antiepileptic drug.","authors":"W M Brown,&nbsp;S P Aiken","doi":"10.1615/critrevneurobiol.v12.i3.30","DOIUrl":"https://doi.org/10.1615/critrevneurobiol.v12.i3.30","url":null,"abstract":"<p><p>Felbamate was launched in 1993 in the U.S. as a \"new generation\" antiepileptic drug (AED) with a unique mechanism of action. It proved efficacious in patients refractory to other AEDs and was particularly beneficial in children suffering from Lennox-Gastaut syndrome, being the first drug shown to be effective at treating this condition in controlled trials. Following the occurrence of rare cases of aplastic anemia and of hepatic failure associated with the use of felbamate during early 1994, a \"black-box\" warning was added to the drug's package insert. Despite this, felbamate continues to be used in many patients, although not as a first-line treatment. Felbamate's dual mechanism of action--enhancing the GABA system while inhibiting excitatory amino acid responses--may explain its efficacy in a broad range of epileptic patients. A better understanding of this mechanism may lead to the development of felbamate-like drugs with a better side effect profile.</p>","PeriodicalId":10778,"journal":{"name":"Critical reviews in neurobiology","volume":"12 3","pages":"205-22"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20755339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serotonin 5-HT2A receptors: molecular biology and mechanisms of regulation.","authors":"B L Roth,&nbsp;S A Berry,&nbsp;W K Kroeze,&nbsp;D L Willins,&nbsp;K Kristiansen","doi":"10.1615/critrevneurobiol.v12.i4.30","DOIUrl":"https://doi.org/10.1615/critrevneurobiol.v12.i4.30","url":null,"abstract":"<p><p>Serotonin 5-HT2A receptors are essential for a large number of physiological functions in the central nervous system and periphery. This review article summarizes our current knowledge of the molecular biology and mechanisms of regulation of 5-HT2A receptors. The mode of drug binding using data derived from molecular modeling and site-directed mutagenesis is described. The cellular and subcellular localization of 5-HT2A receptors is described, and the concentration of 5-HT2A receptors on apical dendrites of pyramidal neurons is emphasized. Various modes of regulation of 5-HT2A receptors are also summarized, including transcriptional, post-translational and mRNA editing processes. Finally, an integrated model of 5-HT2A receptor regulation that involves various protein kinases (protein kinase C, G-protein receptor kinases), arrestins, clathrin-coated vesicles, endosomes and lysosomes. The relevance of these pathways for antidepressant and antipsychotic drug actions is emphasized.</p>","PeriodicalId":10778,"journal":{"name":"Critical reviews in neurobiology","volume":"12 4","pages":"319-38"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21217521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corticosterone and serotonergic neurotransmission in the hippocampus: functional implications of central corticosteroid receptor diversity.","authors":"O C Meijer,&nbsp;E R de Kloet","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The activity of the hippocampus is modulated by a serotonergic projection from the midbrain. Corticosteroids regulate the activity of this raphe-hippocampal system in various ways. These effects are differentially mediated via two types of central corticosteroid receptor types, the high-affinity mineralocorticoid receptor (MR), and the lower affinity glucocorticoid receptor (GR). Under physiological fluctuations of corticosteroid concentrations, predominantly MR-mediated effects suppress the activity of the raphe-hippocampal system, notably serotonin (5-HT)1A receptor-related activity: 5-HT1A receptors are down-regulated, and the cellular response to 5-HT1A receptor activation is attenuated. Transiently increased concentrations of corticosteroids, as induced by stress, result in combined occupation of both MR and GR, and allow increased activity of the raphe-hippocampal system. Stimulatory actions of corticosteroids involving GR occupation include increased responsiveness of hippocampal neurons to 5-HT1A receptor stimulation, attenuated autoinhibition of 5-HT, and a permissive effect on stress-induced increases in 5-HT release. Under (pathological) conditions of chronically elevated corticosteroid concentrations, however, serotonergic neurotransmission is impaired. Human depression is an important example of a condition of combined hypercorticism and an apparent hypoactivity of serotonergic transmission. Deficiency of brain GR function may be genetically determined or acquired by stress. It is proposed that the balance of MR/GR activation can be altered by chronic (stress-related) changes of corticosteroid concentrations, in combination with glucocorticoid feedback resistance. Such an imbalance would lead to a relative dominance of MR-mediated suppressive effects on the activity of the raphe-hippocampal system, which may be a biologically relevant aspect of depression.</p>","PeriodicalId":10778,"journal":{"name":"Critical reviews in neurobiology","volume":"12 1-2","pages":"1-20"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20371901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Animal models of alcoholism: neurobiology of high alcohol-drinking behavior in rodents.","authors":"W J McBride,&nbsp;T K Li","doi":"10.1615/critrevneurobiol.v12.i4.40","DOIUrl":"https://doi.org/10.1615/critrevneurobiol.v12.i4.40","url":null,"abstract":"<p><p>This review discusses efforts to develop rodent models for the study of neurobiological mechanisms underlying chronic alcohol drinking, alcoholism, and abnormal alcohol-seeking behavior. Selective breeding has produced stable lines of rats that reliably exhibit high and (for comparison purposes) low voluntary alcohol consumption. In addition, animal models of chronic ethanol self-administration have been developed in rodents, who do not have a genetic predisposition for high alcohol-seeking behavior, to explore environmental influences in ethanol drinking and the effects of physical dependence on alcohol self-administration. The selectively bred high-preference animals reliably self-administer ethanol by free-choice drinking and operantly respond for oral ethanol in amounts that produce pharmacologically meaningful blood alcohol concentrations (50 to 200 mg% and higher). In addition, the alcohol-preferring rats will self-administer ethanol by intragastric infusion. With chronic free-choice drinking, the high alcohol-preferring rats develop tolerance to the high-dose effects of ethanol and show signs of physical dependence after the withdrawal of alcohol. Compared with nonpreferring animals, the alcohol-preferring rats are less sensitive to the sedative-hypnotic effects of ethanol and develop tolerance more quickly to high-dose ethanol. Nonselected common stock rats can be trained to chronically self-administer ethanol following its initial presentation in a palatable sucrose or saccharin solution, and the gradual replacement of the sucrose or saccharin with ethanol (the sucrose/saccharin-fade technique). Moreover, rats that are trained in this manner and then made dependent by ethanol-vapor inhalation or liquid diet increase their ethanol self-administration during the withdrawal period. Both the selectively bred rats and common-stock rats demonstrate \"relapse\" and an alcohol deprivation effect following 2 or more weeks of abstinence. Systemic administration of agents that (1) increase synaptic levels of serotonin (5-HT) or dopamine (DA); (2) activate 5-HT1A, 5-HT2, D2, D3, or GABA(A) receptors; or (3) block opioid and 5-HT3 receptors decrease ethanol intake in most animal models. Neurochemical, neuroanatomical, and neuropharmacological studies indicate innate differences exist between the high alcohol-consuming and low alcohol-consuming rodents in various CNS limbic structures. In addition, reduced mesolimbic DA and 5-HT function have been observed during alcohol withdrawal in common stock rats. Depending on the animal model under study, abnormalities in the mesolimbic dopamine pathway, and/or the serotonin, opioid, and GABA systems that regulate this pathway may underlie vulnerability to the abnormal alcohol-seeking behavior in the genetic animal models.</p>","PeriodicalId":10778,"journal":{"name":"Critical reviews in neurobiology","volume":"12 4","pages":"339-69"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21217522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reverse physiology: discovery of the novel neuropeptide, orphanin FQ/nociceptin.","authors":"O Civelli, H P Nothacker, R Reinscheid","doi":"10.1615/critrevneurobiol.v12.i3.10","DOIUrl":"10.1615/critrevneurobiol.v12.i3.10","url":null,"abstract":"<p><p>The search for novel neurotransmitters and neuropeptides has been recently revolutionized by the development of a purification strategy based on orphan G protein-coupled receptors, cloned receptors for which no natural ligands are known. This strategy uses the orphan receptor as bait to identify its natural ligand. This article will review the discovery of the first natural ligand isolated following this strategy. This ligand is a peptide that shares some striking sequence similarity to the opioid peptides and has been named Orphanin FQ or Nociceptin (OFQ/NOC). The discovery of OFQ/NOC will be described as one example of the use of orphan receptors in identifying novel neurotransmitters and neuropeptides, an example that has already been followed in the identification of other novel neuropeptides. After reviewing the conceptual and technological basis of the strategy and its successful first application, we discuss the criteria used to validate OFQ/NOC as the natural ligand of the orphan receptor and as a genuine neuropeptide. We also discuss the importance and implications of discovering OFQ/NOC mode of synthesis, which is synthesized as expected in the form of a larger polypeptide precursor, which in turn raises the question of the existence of other OFQ/NOC-related peptides. We then present an overview of the numerous studies that have blossomed after the OFQ/NOC discovery and describe the numerous physiological roles that have already been attributed to OFQ/NOC, and in particular the controversy regarding its involvement in pain perception. Because of the similarities between the OFQ/NOC and opioid systems, we also discuss overlaps between these systems and present evidence favoring a pharmacological separation between these systems. We finish by outlining the power of the orphan receptor strategy and by discussing some of its pitfalls.</p>","PeriodicalId":10778,"journal":{"name":"Critical reviews in neurobiology","volume":"12 3","pages":"163-76"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20755337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social deprivation of neonatal, adolescent, and adult rats has distinct neurochemical and behavioral consequences.","authors":"F S Hall","doi":"10.1615/critrevneurobiol.v12.i1-2.50","DOIUrl":"https://doi.org/10.1615/critrevneurobiol.v12.i1-2.50","url":null,"abstract":"<p><p>This review examines the consequences of social deprivation on brain chemistry and behavior on rats. Although social deprivation produces wide-ranging behavioral and neurochemical effects, it appears that these effects are determined by a number of factors, the most critical factor being the age or developmental stage during the period of deprivation. Roughly, the effects examined in this review may be separated into three major developmental stages and each is related to deprivation of specific types of social interaction: preweaning/neonatal, postweaning/adolescent, and adult. The effects of social deprivation during each of these stages appears to be neurochemically and behaviorally specific. However, much of the research to date has failed to examine deprivation during specific stages, often combining deprivation of different types. Nonetheless, these modifications of experience produce animals of differing phenotypes, which could be characterized as pathological in nature in many instances, and may model particular aspects of human psychopathologies or perhaps the propensity to develop those phenotypic features.</p>","PeriodicalId":10778,"journal":{"name":"Critical reviews in neurobiology","volume":"12 1-2","pages":"129-62"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20373879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitric oxide in cerebral ischemic neurodegeneration and excitotoxicity.","authors":"P J Strijbos","doi":"10.1615/critrevneurobiol.v12.i3.40","DOIUrl":"https://doi.org/10.1615/critrevneurobiol.v12.i3.40","url":null,"abstract":"<p><p>The observation that the free radical nitric oxide (NO) acts as a cell signaling molecule in key physiological processes such as regulation of blood pressure and immunological host-defense responses is probably one of the most important and exciting findings made in biology in the last decade. Likewise, in the brain NO has been implicated in a number of fundamental processes, including memory formation, sexual behavior and the control of cerebral blood flow. This has radically altered the accepted dogma of brain physiology and has placed NO at the center stage of neuroscience research. Evidence suggests that some of the actions of NO in the brain may be intimately linked to those of the classic excitatory neurotransmitter glutamate. The historical view that aberrations in glutamate signal transduction may underlie central neurodegeneration following, for example, cerebral ischemia, has implicated NO, by default, as a potential mediator of neuronal death. Indeed, with the advent of potent and specific compounds that interact with NO synthesizing (NOS) enzymes and with the NO signaling cascade, there is now ample evidence to suggest that NO can mediate neurodegeneration, although its involvement is paradoxical. Its cerebrovascular effects may act to limit ischemic damage by preserving tissue perfusion and preventing platelet aggregation, while NO produced in the parenchyma, either directly following the ischemic insult or at a later stage as part of a neuroinflammatory response, may be deleterious to the outcome of ischemia. Nonetheless, significant efforts are made into the potential therapeutic use of chemical NO donors and specific NOS inhibitors in the treatment of cerebral ischemia and other central neurodegenerative disorders. Here, the latest concepts and developments in our understanding of the role of NO in cerebral ischemic neurodegeneration are discussed.</p>","PeriodicalId":10778,"journal":{"name":"Critical reviews in neurobiology","volume":"12 3","pages":"223-43"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20756536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}