NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics最新文献_第8页

Pharmacological Treatments that Facilitate Extinction of Fear: Relevance to Psychotherapy 促进恐惧消除的药物治疗:与心理治疗相关

NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics Pub Date : 2006-01-01 DOI: 10.1016/j.nurx.2005.12.008

Michael Davis, Karyn M. Myers, Jasmeer Chhatwal, Kerry J. Ressler

{"title":"Pharmacological Treatments that Facilitate Extinction of Fear: Relevance to Psychotherapy","authors":"Michael Davis, Karyn M. Myers, Jasmeer Chhatwal, Kerry J. Ressler","doi":"10.1016/j.nurx.2005.12.008","DOIUrl":"10.1016/j.nurx.2005.12.008","url":null,"abstract":"<div><h3>Summary</h3><p>A great deal is now known about the mechanisms of conditioned fear acquisition and expression. More recently, the mechanisms of inhibition of conditioned fear have become the subject of intensive study. The major model system for the study of fear inhibition in the laboratory is extinction, in which a previously fear conditioned organism is exposed repeatedly to the fear-eliciting cue in the absence of any aversive event and the fear conditioned response declines. It is well established that extinction is a form of new learning as opposed to forgetting or “unlearning” of conditioned fear, and it is hypothesized that extinction develops when sensory pathways conveying sensory information to the amygdala come to engage GABAergic interneurons through forms of experience-dependent plasticity such as long-term potentiation. Several laboratories currently are investigating methods of facilitating fear extinction in animals with the hope that such treatments might ultimately prove to be useful in facilitating exposure-based therapy for anxiety disorders in clinical populations. This review discusses the advances that have been made in this field and presents the findings of the first major clinical study to examine the therapeutic utility of a drug that facilitates extinction in animals. It is concluded that extinction is an excellent model system for the study of fear inhibition and an indispensable tool for the screening of putative pharmacotherapies for clinical use.</p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"3 1","pages":"Pages 82-96"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nurx.2005.12.008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25865798","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}

引用次数: 130

Glutamate-Modulating Drugs as Novel Pharmacotherapeutic Agents in the Treatment of Obsessive-Compulsive Disorder 谷氨酸调节药物作为治疗强迫症的新型药物

NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics Pub Date : 2006-01-01 DOI: 10.1016/j.nurx.2005.12.006

Christopher Pittenger, John H. Krystal, Vladimir Coric

{"title":"Glutamate-Modulating Drugs as Novel Pharmacotherapeutic Agents in the Treatment of Obsessive-Compulsive Disorder","authors":"Christopher Pittenger, John H. Krystal, Vladimir Coric","doi":"10.1016/j.nurx.2005.12.006","DOIUrl":"10.1016/j.nurx.2005.12.006","url":null,"abstract":"<div><h3>Summary</h3><p>Obsessive-compulsive disorder (OCD) is a common psychiatric disorder that produces significant morbidity. The introduction of serotonin reuptake inhibitors in the 1980s represented an important advance in the treatment of OCD. However, few patients show complete remission of their symptoms, and some patients show minimal improvement with existing treatments. We review current treatment strategies and initial data supporting the efficacy of glutamate modulating agents as a novel class of pharmaceuticals for the treatment of OCD. Functional neuroimaging studies repeatedly reported metabolic hyperactivity in the cortico-striato-thalamo-cortical circuitry in patients with OCD. Recent magnetic resonance spectroscopy studies provide evidence of elevated glutamate levels in several brain regions in patients suffering from OCD. These findings raised the possibility that agents that reduce glutamate hyperactivity or its consequences in the CNS might be efficacious as novel therapeutic interventions. Indeed, initial evidence from our group suggests that the antiglutamatergic agent riluzole (Rilutek), which was developed for the treatment of amyotrophic lateral sclerosis, is effective in treatment-resistant OCD. Case reports suggest that other agents that modulate glutamatergic activity may likewise be effective. This new application of glutamate modulating agents holds promise for the treatment of this disabling and often inadequately treated disease.</p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"3 1","pages":"Pages 69-81"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nurx.2005.12.006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25865796","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}

引用次数: 163

Imaging Genomics and Response to Treatment with Antipsychotics in Schizophrenia 精神分裂症患者影像学基因组学与抗精神病药物治疗反应

NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics Pub Date : 2006-01-01 DOI: 10.1016/j.nurx.2005.12.001

Giuseppe Blasi , Alessandro Bertolino

{"title":"Imaging Genomics and Response to Treatment with Antipsychotics in Schizophrenia","authors":"Giuseppe Blasi , Alessandro Bertolino","doi":"10.1016/j.nurx.2005.12.001","DOIUrl":"10.1016/j.nurx.2005.12.001","url":null,"abstract":"<div><p>Recent important advancements in genomic research have opened the way to new strategies for public health management. One of these questions pertains to how individual genetic variation may be associated with individual variability in response to drug treatment. The field of pharmacogenetics may have a profound impact on treatment of complex psychiatric disorders like schizophrenia. However, pharmacogenetic studies in schizophrenia have produced conflicting results. The first studies examined potential associations between clinical response and drug receptor genes. Subsequent studies have tried to use more objective phenotypes still in association with drug receptor genes. More recently, other studies have sought the association between putative causative or modifier genes and intermediate phenotypes. Thus, conflicting results may be at least in part explained by variability and choice of the phenotype, by choice of candidate genes, or by the relatively little knowledge about the neurobiology of this disorder. We propose that choosing intermediate phenotypes that allow <em>in vivo</em> measurement of specific neuronal functions may be of great help in reducing several of the potential confounds intrinsic to clinical measurements. Functional neuroimaging is ideally suited to address several of these potential confounds, and it may represent a powerful strategy to investigate the relationship between behavior, brain function, genes, and individual variability in the response to treatment with antipsychotic drugs in schizophrenia. Preliminary evidence with potential susceptilibity genes such as COMT, DISC1, and GRM3 support these assumptions.</p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"3 1","pages":"Pages 117-130"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nurx.2005.12.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25865802","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}

引用次数: 18

Finding What You Are Not Looking for: Strategies for Developing Novel Treatments in Psychiatry 找到你没有寻找的:精神病学新疗法的发展策略

NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics Pub Date : 2006-01-01 DOI: 10.1016/j.nurx.2005.12.002

Stephen M. Stahl

{"title":"Finding What You Are Not Looking for: Strategies for Developing Novel Treatments in Psychiatry","authors":"Stephen M. Stahl","doi":"10.1016/j.nurx.2005.12.002","DOIUrl":"10.1016/j.nurx.2005.12.002","url":null,"abstract":"<div><h3>Summary</h3><p>Psychopharmacological treatments in psychiatry are often surprises. Original targets frequently fail, and when successful, may only be the opening volley in a series of ever more important therapeutic applications. Drug development may begin by hypothesis-driven targeting of therapeutic indications with an agent of known and novel mechanism of action. Although this may generate a highly feasible therapeutic indication and can proceed by a well-worn regulatory pathway with known approvable endpoints, it may not only be the least innovative but also the least commercially successful strategy. Because surrogate markers of efficacy are only theoretically attractive but still largely elusive for psychiatric disorders, drug development strategies may need to proceed instead by opportunistic capturing of signals from clinical use of new agents once they enter clinical practice. Outcomes and dosing for clinical trial populations may not match those in clinical practice, so observations from clinical practice must feed back into new clinical trials. In many ways, once efficacy is proven for the originally targeted indication, drug development begins afresh. To get to secondary stages of novel indications for psychiatric drugs and thus to maximize each drug’s therapeutic potential, evidence-based prescribing is followed by prescribing-based evidence, namely feedback from clinical practice into clinical proof-of-concept studies followed by large-scale studies and new indications. In many cases, the new indications are the more important therapeutic contributions and the most successful commercial application of a drug. Here we describe this strategy of psychiatric drug development and provide numerous examples.</p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"3 1","pages":"Pages 3-9"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nurx.2005.12.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25866378","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}

引用次数: 11

Pharmacogenetic Tools for the Development of Target-Oriented Cognitive-Enhancing Drugs 面向目标的认知增强药物开发的药物遗传学工具

NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics Pub Date : 2006-01-01 DOI: 10.1016/j.nurx.2005.12.004

José A. Apud, Daniel R. Weinberger

{"title":"Pharmacogenetic Tools for the Development of Target-Oriented Cognitive-Enhancing Drugs","authors":"José A. Apud, Daniel R. Weinberger","doi":"10.1016/j.nurx.2005.12.004","DOIUrl":"10.1016/j.nurx.2005.12.004","url":null,"abstract":"<div><p><span><span><span>The identification of the anatomical and physiological substrates involved in the regulation of the dorsolateral prefrontal cortex function in humans provided the basis for the understanding of mechanisms involved in cognitive and executive function under normal as well as pathological conditions. In this context, substantial evidence indicates that alterations in monaminergic function in the dorsolateral prefrontal cortex significantly contributes to the cognitive impairments present in schizophrenia, </span>attention deficit disorders<span>, and other neuropsychiatric conditions. The development of a number of compounds that selectively increase extracellular dopamine (DA) concentrations in the dorsolateral prefrontal cortex but not in subcortical areas by either blocking its metabolism or reuptake, or increasing its release, or that directly activate postsynaptic<span> DA-1 receptor mechanisms provided powerful pharmacotherapeutic tools to mitigate the cognitive deficits brought about by the </span></span></span>dopaminergic alterations of the prefrontal cortex. More recently, the findings that polymorphisms of the catecholamine-</span><em>O</em>-methyl-transferase gene may also modify the effect of these drugs on the prefrontal cortex points toward a more specific genotype-based neuropsychopharmacology for the treatment of cognitive deficits in schizophrenia as well as in a number of other neuropsychiatric conditions. The ability of these compounds to increase DA load selectively in the frontal cortex and not on subcortical systems allows a targeted intervention without the stimulant-like effects observed with older drugs used to treat those conditions.</p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"3 1","pages":"Pages 106-116"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nurx.2005.12.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25865800","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}

引用次数: 10

New Directions in Psychiatric Therapeutics 精神病学治疗的新方向

NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics Pub Date : 2006-01-01 DOI: 10.1016/j.nurx.2005.12.011

Daniel R. Weinberger (Guest Editor)

引用次数: 2

How Antipsychotics Work—From Receptors to Reality 抗精神病药物是如何起作用的——从受体到现实。

NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics Pub Date : 2006-01-01 DOI: 10.1016/j.nurx.2005.12.003

Shitij Kapur , Ofer Agid , Romina Mizrahi , Ming Li

{"title":"How Antipsychotics Work—From Receptors to Reality","authors":"Shitij Kapur , Ofer Agid , Romina Mizrahi , Ming Li","doi":"10.1016/j.nurx.2005.12.003","DOIUrl":"10.1016/j.nurx.2005.12.003","url":null,"abstract":"<div><p>How does a small molecule blocking a few receptors change a patients’ passionately held paranoid belief that the FBI is out to get him? To address this central puzzle of antipsychotic action, we review a framework linking dopamine neurochemistry to psychosis, and then link this framework to the mechanism of action of antipsychotics. Normal dopamine transmission has a role in predicting novel rewards and in marking and responding to motivationally salient stimuli. Abnormal dopamine transmission alters these processes and results in an aberrant sense of novelty and inappropriate assignment of salience leading to the experience of psychosis. Antipsychotics improve psychosis by diminishing this abnormal transmission by blocking the dopamine D2/3 receptor (not D1 or D4), and although several brain regions may be involved, it is suggested that the ventral striatal regions (analog of the nucleus accumbens in animals) may have a particularly critical role. Contrary to popular belief, the antipsychotic effect is not delayed in its onset, but starts within the first few days. There is more improvement in the first 2 weeks, than in any subsequent 2-week period thereafter. However, a simple organic molecule cannot target the complex phenomenology of the individual psychotic experience. Antipsychotics diminish dopamine transmission and thereby dampen the salience of the preoccupying symptoms. Therefore, in the initial stage of an antipsychotic response, the patients experience a detachment from symptoms, a relegation of the delusions and hallucinations to the back of their minds, rather than a complete erasure of the symptoms. Only with time, and only in some, via the mediation of new learning and plasticity, is there a complete resolution of symptoms. The implications of these findings for clinical care, animal models, future target discovery and drug development are discussed.</p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"3 1","pages":"Pages 10-21"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nurx.2005.12.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25866379","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}

引用次数: 75

Catechol-O-Methyltransferase Polymorphisms and Some Implications for Cognitive Therapeutics 儿茶酚o -甲基转移酶多态性及其对认知治疗的影响。

NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics Pub Date : 2006-01-01 DOI: 10.1016/j.nurx.2005.12.010

Catherine M. Diaz-Asper, Daniel R. Weinberger, Terry E. Goldberg

{"title":"Catechol-O-Methyltransferase Polymorphisms and Some Implications for Cognitive Therapeutics","authors":"Catherine M. Diaz-Asper, Daniel R. Weinberger, Terry E. Goldberg","doi":"10.1016/j.nurx.2005.12.010","DOIUrl":"10.1016/j.nurx.2005.12.010","url":null,"abstract":"<div><p>Catechol-O-methyltransferase (COMT) is a gene involved in the degradation of dopamine and may both increase susceptibility to develop schizophrenia and affect neuronal functions involved in working memory. A common variant of the COMT gene (val<sup>108/158</sup>met) has been widely reported to affect prefrontally mediated working memory function, with the high-activity val allele associated with poorest performance across a number of tests sensitive to updating and target detection. Pharmacological manipulations of COMT val<sup>108/158</sup>met also have reliably produced alterations in cognitive function, in line with an inverted U function of prefrontal dopamine signaling. Furthermore, there is accumulating evidence that COMT val<sup>108/158</sup>met genotype may influence the cognitive response to antipsychotic treatment in schizophrenia patients, with met allele load predicting the greatest improvement with medication. Recently, other single-nucleotide polymorphisms (SNPs) across the COMT gene have emerged as possible risk alleles for schizophrenia, although little is known about whether they affect prefrontal cognition in a manner similar to COMT val<sup>108/158</sup>met. Preliminary evidence suggests a modest role for a SNP in the 5′ region of the gene on select tests of attention and target detection. Haplotype effects also may account for a modest percentage of the variance in test performance, and are an important area for future study.</p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"3 1","pages":"Pages 97-105"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.nurx.2005.12.010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25865799","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}

引用次数: 30

Developing Therapeutics for Schizophrenia and Other Psychotic Disorders 发展精神分裂症和其他精神障碍的治疗方法

NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics Pub Date : 2005-10-01 DOI: 10.1602/neurorx.2.4.579

Gerard Marek, Kalpana Merchant

{"title":"Developing Therapeutics for Schizophrenia and Other Psychotic Disorders","authors":"Gerard Marek, Kalpana Merchant","doi":"10.1602/neurorx.2.4.579","DOIUrl":"10.1602/neurorx.2.4.579","url":null,"abstract":"<div><p>Although the second-generation or atypical antipsychotic drugs have been breakthrough medicines for the treatment of schizophrenia and other psychotic conditions, cognitive dysfunction and to some extent negative symptoms of the disease continue to be the main cause of poor vocational status of the patients. Thus, the majority of investigational drug development efforts today target these unmet medical needs. This review postulates that the field of schizophrenia research has advanced sufficiently to develop biochemical hypotheses of the etiopathology of the disease and target the same for revolutionary disease modifying therapy. This postulate is based on recent studies that have begun to provide a testable etiopathology model that integrates interactions between genetic vulnerability factors, neurodevelopmental anomalies, and neurotransmitter systems. This review begins with a brief overview of the nosology and etiopathology of schizophrenia and related psychotic disorders to establish a context for subsequent detailed discussions on drug discovery and development for psychotic disorders. Particular emphasis is placed on recent advances in genetic association studies of schizophrenia and how this can be integrated with evidence supporting neurodevelopmental abnormalities associated with the disease to generate a testable model of the disease etiopathology. An in-depth review of the plethora of new targets and approaches targeting the unmet medical need in the treatment of schizophrenia exemplify the challenges and opportunities in this area. We end the review by offering an approach based on emerging genetic, clinical, and neurobiological studies to discover and validate novel drug targets that could be classified as disease modifying approaches.</p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"2 4","pages":"Pages 579-589"},"PeriodicalIF":0.0,"publicationDate":"2005-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1602/neurorx.2.4.579","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25864686","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}

引用次数: 20

Innovative Approaches for the Development of Antidepressant Drugs: Current and Future Strategies 抗抑郁药物开发的创新方法:当前和未来的策略

NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics Pub Date : 2005-10-01 DOI: 10.1602/neurorx.2.4.590

Dr. Lee E. Schechter, Robert H. Ring, Chad E. Beyer, Zoë A. Hughes, Xavier Khawaja, Jessica E. Malberg, Sharon Rosenzweig-Lipson

{"title":"Innovative Approaches for the Development of Antidepressant Drugs: Current and Future Strategies","authors":"Dr. Lee E. Schechter, Robert H. Ring, Chad E. Beyer, Zoë A. Hughes, Xavier Khawaja, Jessica E. Malberg, Sharon Rosenzweig-Lipson","doi":"10.1602/neurorx.2.4.590","DOIUrl":"10.1602/neurorx.2.4.590","url":null,"abstract":"<div><p>Depression is a highly debilitating disorder that has been estimated to affect up to 21% of the world population. Despite the advances in the treatment of depression with selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), there continue to be many unmet clinical needs with respect to both efficacy and side effects. These needs range from efficacy in treatment resistant patients, to improved onset, to reductions in side effects such as emesis or sexual dysfunction. To address these needs, there are numerous combination therapies and novel targets that have been identified that may demonstrate improvements in one or more areas. There is tremendous diversity in the types of targets and approaches being taken. At one end of a spectrum is combination therapies that maintain the benefits associated with SSRIs but attempt to either improve efficacy or reduce side effects by adding additional mechanisms (5-HT<sub>1A</sub>, 5-HT<sub>1B</sub>, 5-HT<sub>1D</sub>, 5-HT<sub>2C</sub>, α-2A). At the other end of the spectrum are more novel targets, such as neurotrophins (BDNF, IGF), based on recent findings that antidepressants induce neurogenesis. In between, there are many approaches that range from directly targeting serotonin receptors (5-HT<sub>2C</sub>, 5-HT<sub>6</sub>) to targeting the multiplicity of potential mechanisms associated with excitatory (glutamate, NMDA, mGluR2, mGluR5) or inhibitory amino acid systems (GABA) or peptidergic systems (neurokinin 1, corticotropin-releasing factor 1, melanin-concentrating hormone 1, V1b). The present review addresses the most exciting approaches and reviews the localization, neurochemical and behavioral data that provide the supporting rationale for each of these targets or target combinations.</p></div>","PeriodicalId":87195,"journal":{"name":"NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics","volume":"2 4","pages":"Pages 590-611"},"PeriodicalIF":0.0,"publicationDate":"2005-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1602/neurorx.2.4.590","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25864687","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}

引用次数: 176