Synapse (New York, N.y.)最新文献

Dopamine-transporter heterozygous rats carrying maternal wild-type allele are more vulnerable to the development of compulsive behavior. 携带母体野生型等位基因的多巴胺转运杂合大鼠更易产生强迫行为。

IF 2.3

Synapse (New York, N.y.) Pub Date : 2022-08-01 Epub Date: 2022-07-15 DOI: 10.1002/syn.22244

Fabiana Festucci, Eugenia Annunzi, Martina Pepe, Giuseppe Curcio, Claudio D'Addario, Walter Adriani

{"title":"Dopamine-transporter heterozygous rats carrying maternal wild-type allele are more vulnerable to the development of compulsive behavior.","authors":"Fabiana Festucci, Eugenia Annunzi, Martina Pepe, Giuseppe Curcio, Claudio D'Addario, Walter Adriani","doi":"10.1002/syn.22244","DOIUrl":"https://doi.org/10.1002/syn.22244","url":null,"abstract":"Compulsivity is defined as an unstoppable tendency toward repetitive and habitual actions, which are reiterated despite negative consequences. Polydipsia is induced preclinically by intermittent reward, leading rodents to ingest large amounts of fluids. We focused on the role of dopamine transporter (DAT) and inheritance factors in compulsive behavior. Our sample consisted of DAT heterozygous (HET) rats with different genetic inheritance (MAT-HET, born from WT-dams × KO-fathers; MIX-HET, born from HET-dams × KO-fathers). As controls, we used both wild-type (WT) rats and their socially-isolated (WTi) siblings. We ran the schedule-induced polydipsia (SIP) protocol, to induce compulsive behavior; then the Y-maze and marble-burying tests, to verify its actual development. Only MAT-HET (who inherited the functional DAT allele from the WT mother) is vulnerable to developing compulsive behavior. MAT-HET rats drank increasingly more water during SIP; they showed significant perseverance in the Y-maze test and exhibited compulsive actions in the marble-burying test. Interestingly, compulsive behaviors of MAT-HET rats correlated with expression ex vivo of different genes in different areas. Regarding the prefrontal cortex (PFC), D2R correlated with Y-maze \"perseverance\" in addition to BDNF; considering the amygdala (AMY), both D3R and OXTR correlated with SIP \"licks.\" Indeed, compulsivity may be linked to D2R and BDNF in PFC, while extreme anxiety in MAT-HET rats may be associated with D3R and OXTR in the AMY. These results confirm some similarities between MAT-HET and DAT-KO subjects, and link the epigenetic context of the DAT gene to the development of compulsive behavior.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"31-44"},"PeriodicalIF":2.3,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40466231","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: 4

Abstinence following intermittent methylphenidate exposure dose-dependently modifies brain glucose metabolism in the rat brain. 间歇性哌甲酯暴露后的戒断剂量依赖性改变了大鼠脑中的葡萄糖代谢。

IF 2.3

Synapse (New York, N.y.) Pub Date : 2022-08-01 Epub Date: 2022-06-30 DOI: 10.1002/syn.22243

Eliz Arnavut, John Hamilton, Rutao Yao, Munawwar Sajjad, Michael Hadjiargyrou, David Komatsu, Panayotis K Thanos

{"title":"Abstinence following intermittent methylphenidate exposure dose-dependently modifies brain glucose metabolism in the rat brain.","authors":"Eliz Arnavut, John Hamilton, Rutao Yao, Munawwar Sajjad, Michael Hadjiargyrou, David Komatsu, Panayotis K Thanos","doi":"10.1002/syn.22243","DOIUrl":"https://doi.org/10.1002/syn.22243","url":null,"abstract":"Methylphenidate (MP) is a psychostimulant chronically prescribed for the treatment of attention deficit hyperactivity disorder (ADHD). Additionally, MP users may take breaks from using the medication during \"drug holidays,\" which may include short-term or long-term breaks from medication. The present study utilized fluorodeoxyglucose (FDG) positron emission tomography (PET) to analyze the effects of chronic oral MP use and abstinence on brain glucose metabolism (BGluM) in rats at two different doses: high dose (HD) and low dose (LD). The schedule of treatment was 3 weeks on-treatment and 1 week off-treatment for a period of 13 weeks, followed by an abstinence period of 4 total weeks. Results showed that chronic MP treatment using this schedule did not lead to significant changes in BGluM when comparing the control to HD MP groups. However, significant activation in BGluM was observed after periods of abstinence between control and HD MP rats in the following brain regions: the trigeminal nucleus, reticular nucleus, inferior olive, lemniscus, mesencephalic reticular formation, inferior colliculus, and several areas of the cerebellum. These brain regions and functional brain circuit play a role in facial sensory function, the auditory pathway, organizing connections between the thalamus and cortex, motor learning, auditory function, control over eye movement, auditory information integration, and both motor and cognitive functions. These results, when considered with previous studies, indicate that MP schedule of use may have differing effects on BGluM. BGluM following long-term MP use was dependent on MP dose and schedule of use in rats. This study was conducted in non-ADHD model rats with the aim to establish an understanding of the effects of MP itself, especially given the growing chronic off-label and prescribed use of MP. Further studies are needed for analysis of the drug's effects on an ADHD model.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"17-30"},"PeriodicalIF":2.3,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40164838","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: 1

Effects of selective orexin receptor-2 and cannabinoid receptor-1 antagonists on the response of medial prefrontal cortex neurons to tramadol. 选择性食欲素受体-2和大麻素受体-1拮抗剂对内侧前额皮质神经元对曲马多反应的影响。

IF 2.3

Synapse (New York, N.y.) Pub Date : 2022-06-01 Epub Date: 2022-03-29 DOI: 10.1002/syn.22232

Neda Hasanpour Razmanjani, Parham Reisi

{"title":"Effects of selective orexin receptor-2 and cannabinoid receptor-1 antagonists on the response of medial prefrontal cortex neurons to tramadol.","authors":"Neda Hasanpour Razmanjani, Parham Reisi","doi":"10.1002/syn.22232","DOIUrl":"https://doi.org/10.1002/syn.22232","url":null,"abstract":"Tramadol is widely used to control pain in various diseases, but the relevant mechanisms are less known despite the severe risks of abuse. The medial prefrontal cortex (mPFC) is one of the critical centers of the reward system. Studies have shown that orexins and endocannabinoids are likely to play an important role in addiction. In this study, the effect of orexin receptor‐2 (OX2R) and endocannabinoid receptor‐1 (CB1R) blockade on the neuronal activity of mPFC was investigated in response to tramadol in male rats. Tramadol was injected intraperitoneally, and its effects on the firing of mPFC pyramidal neurons were investigated using in vivo extracellular single‐unit recording. Tramadol affected the pyramidal neuronal activity of the mPFC. AM251 (18 nmol/4 μl), as a selective CB1R antagonist, and TCS‐OX2‐29 (50 nmol/4 μl), as a selective OX2R antagonist, individually or simultaneously were microinjected into the lateral ventricle of the brain (intracerebroventricular, ICV). The results showed that the ratio of neurons with the excitatory/inhibitory or no responses was significantly changed by tramadol (p < .05). These changes were prevented by blockade of CB1Rs alone or blockade of OX2Rs and CB1Rs simultaneously (p < .05). However, blockade of these receptors in the vehicle group had no significant effect on neuronal activity. The findings of this study indicate the potential role of orexin and endocannabinoid systems in mediating the effects of tramadol in mPFC and the possible interaction between the two systems via OX2 and CB1 receptors. However, further studies are needed to identify these effects by examining intracellular signaling.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"e22232"},"PeriodicalIF":2.3,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40311965","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: 1

Decreased 5‐HT1A binding in mild Alzheimer's disease—A positron emission tomography study 轻度阿尔茨海默病中5‐HT1A结合减少——正电子发射断层扫描研究

Synapse (New York, N.y.) Pub Date : 2022-05-19 DOI: 10.1002/syn.22235

Patrik Mattsson, Z. Cselényi, B. Andrée, J. Borg, S. Nag, C. Halldin, L. Farde

{"title":"Decreased 5‐HT1A binding in mild Alzheimer's disease—A positron emission tomography study","authors":"Patrik Mattsson, Z. Cselényi, B. Andrée, J. Borg, S. Nag, C. Halldin, L. Farde","doi":"10.1002/syn.22235","DOIUrl":"https://doi.org/10.1002/syn.22235","url":null,"abstract":"Decreased 5‐HT1A receptor binding has been associated with Alzheimer's disease (AD) and interpreted as a consequence of neuron loss. The purpose of the present study was to compare [11C]WAY100635 binding to the 5‐HT1A receptor in the hippocampus, entorhinal cortex, amygdala and pericalcarine cortex in mild AD patients and elderly controls. AD patients (n = 7) and elderly control subjects (n = 8) were examined with positron emission tomography (PET) and [11C]WAY100635. PET data acquisition was performed with an ECAT EXACT HR system. Wavelet‐aided parametric images of nondisplaceable binding potential (BPND) were generated using Logan's graphical analysis with cerebellum as the reference region. Correction for partial volume effects was performed with the Müller–Gärtner method. Regions of interest (ROIs) were applied to the individual parametric images, and the regional BPND was calculated as the average parametric voxel value within each ROI. In addition to comparisons between subject groups, correlations between BPND values and scores on the Mini‐Mental State Examination, Disability Assessment for Dementia (DAD), and Neuropsychiatric Inventory were expressed by Pearson correlation coefficients. Mean regional BPND was lower in AD patients than in control subjects, and the difference was statistically significant for the hippocampus, entorhinal cortex, and amygdala. A statistically significant correlation was obtained between hippocampal BPND values and DAD scores. The results of the present study corroborate and extend previous findings of decreased 5‐HT1A binding in AD and strengthen the support for 5‐HT1A receptor PET as a tool for the assessment of neurodegenerative changes in mild AD.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":"51 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132682319","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: 0

Homeostatic control of Drosophila neuromuscular junction function 果蝇神经肌肉连接功能的稳态控制

Synapse (New York, N.y.) Pub Date : 2019-10-04 DOI: 10.1002/syn.22133

C. Andrew Frank, Thomas D. James, Martin Müller

引用次数: 47

Synaptic signals mediated by protons and acid-sensing ion channels. 质子和酸感离子通道介导的突触信号。

IF 2.3

Synapse (New York, N.y.) Pub Date : 2019-10-01 Epub Date: 2019-07-15 DOI: 10.1002/syn.22120

Osvaldo D Uchitel, Carlota González Inchauspe, Carina Weissmann

{"title":"Synaptic signals mediated by protons and acid-sensing ion channels.","authors":"Osvaldo D Uchitel, Carlota González Inchauspe, Carina Weissmann","doi":"10.1002/syn.22120","DOIUrl":"https://doi.org/10.1002/syn.22120","url":null,"abstract":"Extracellular pH changes may constitute significant signals for neuronal communication. During synaptic transmission, changes in pH in the synaptic cleft take place. Its role in the regulation of presynaptic Ca2+ currents through multivesicular release in ribbon-type synapses is a proven phenomenon. In recent years, protons have been recognized as neurotransmitters that participate in neuronal communication in synapses of several regions of the CNS such as amygdala, nucleus accumbens, and brainstem. Protons are released by nerve stimulation and activate postsynaptic acid-sensing ion channels (ASICs). Several types of ASIC channels are expressed in the peripheral and central nervous system. The influx of Ca2+ through some subtypes of ASICs, as a result of synaptic transmission, agrees with the participation of ASICs in synaptic plasticity. Pharmacological and genetical inhibition of ASIC1a results in alterations in learning, memory, and phenomena like fear and cocaine-seeking behavior. The recognition of endogenous molecules, such as arachidonic acid, cytokines, histamine, spermine, lactate, and neuropeptides, capable of inhibiting or potentiating ASICs suggests the existence of mechanisms of synaptic modulation that have not yet been fully identified and that could be tuned by new emerging pharmacological compounds with potential therapeutic benefits.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"e22120"},"PeriodicalIF":2.3,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.22120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40542451","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: 21

Molecular neurochemistry of the lanthanides. 镧系元素的分子神经化学。

IF 2.3

Synapse (New York, N.y.) Pub Date : 2019-09-01 Epub Date: 2019-06-22 DOI: 10.1002/syn.22119

Artur Pałasz, Yolanda Segovia, Rafał Skowronek, John J Worthington

{"title":"Molecular neurochemistry of the lanthanides.","authors":"Artur Pałasz, Yolanda Segovia, Rafał Skowronek, John J Worthington","doi":"10.1002/syn.22119","DOIUrl":"https://doi.org/10.1002/syn.22119","url":null,"abstract":"Lanthanides, once termed rare-earth elements, are not as sparce in the environment as their traditional name suggests. Mean litospheric concentrations are in fact comparable to the physiologically fundamental elements such as iodine, cobalt, and selenium. Recent advances in medical technology have resulted in accumulation of lanthanides presenting potential exposure to both our central and peripheral nervous systems. Extensive and detailed studies on these peculiar active metals in the context of their influence on neural functions are therefore urgently required. Almost all neurochemical effects of trivalent lanthanide ions appear to result from the similarity of their radii to the key signaling ion calcium. Lanthanides, especially La3+ and Gd3+ block different types of calcium, potassium, and sodium channels in human and animal neurons, regulate neurotransmitter turnover and release, as well as synaptic activity. Lanthanides also act as modulators of several ionotropic receptors, e.g., GABA, NMDA, and kainate and can also affect numerous signaling mechanisms including NF-κB and apoptotic-related endoplasmic reticulum IRE1-XBP1, PERK, and ATF6 pathways. Several lanthanide ions may cause oxidative neuronal injuries and functional impairment by promoting reactive oxygen species production. However, cerium and yttrium oxides have some unique and promising neuroprotective properties, being able to decrease free radical cell injury and even alleviate motor impairment and cognitive function in animal models of multiple sclerosis and mild traumatic brain damage, respectively. In conclusion, lanthanides affect various neurophysiological processes, altering a large spectrum of brain functions. Thus, a deeper understanding of their potential mechanistic roles during disease and as therapeutic agents requires urgent elucidation.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"e22119"},"PeriodicalIF":2.3,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.22119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40561462","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: 15

Combination of BMSCs-laden acellular nerve xenografts transplantation and G-CSF administration promotes sciatic nerve regeneration. 骨髓间充质干细胞脱细胞神经异种移植联合G-CSF可促进坐骨神经再生。

IF 2.3

Synapse (New York, N.y.) Pub Date : 2019-07-01 Epub Date: 2019-03-20 DOI: 10.1002/syn.22093

Hua Jia, Ying Wang, Jiao Chen, Jun-Ping Li, Huai-Qin Han, Xiao-Jie Tong, Zhong-Yi He, Wen-Zhi Ma

{"title":"Combination of BMSCs-laden acellular nerve xenografts transplantation and G-CSF administration promotes sciatic nerve regeneration.","authors":"Hua Jia, Ying Wang, Jiao Chen, Jun-Ping Li, Huai-Qin Han, Xiao-Jie Tong, Zhong-Yi He, Wen-Zhi Ma","doi":"10.1002/syn.22093","DOIUrl":"https://doi.org/10.1002/syn.22093","url":null,"abstract":"Peripheral nerve gaps often lead to interrupted innervation, manifesting as severe sensory and motor dysfunctions. The repairs of the nerve injuries have not achieved satisfactory curative effects in clinic. The transplantation of bone marrow stromal cells (BMSCs)-laden acellular nerve xenografts (ANX) has been proven more effective than the acellular nerve allografting. Besides, granulocyte colony-stimulating factor (G-CSF) can inhibit inflammation and apoptosis, and thus is conducive to the microenvironmental improvement of axonal regeneration. This study aims to investigate the joint effect of BMSCs-seeded ANX grafting and G-CSF administration, and explore the relevant mechanisms. Adult SD rats were divided into five groups randomly: ANX group, ANX combined with G-CSF group, BMSCs-laden ANX group, BMSCs-laden ANX combined with G-CSF group, and autograft group. Eight weeks after transplantation, the detection of praxiology and neuroelectrophysiology was conducted, and then the morphology of the regenerated nerves was analyzed. The inflammatory response and apoptosis in the nerve grafts as well as the expression of the growth-promoting factors in the regenerated tissues were further assayed. G-CSF intervention and BMSCs implanting synergistically promoted peripheral nerve regeneration and functional recovery following ANX bridging, and the restoration effect was matchable with that of the autologous nerve grafting. Moreover, local inflammation was alleviated, the apoptosis of the seeded BMSCs was decreased, and the levels of the neuromodulatory factors were elevated. In conclusion, the union application of BMSCs-implanted ANX and G-CSF ameliorated the niche of neurotization and advanced nerve regeneration substantially. The strategy achieved the favorable effectiveness as an alternative to the autotransplantation.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"e22093"},"PeriodicalIF":2.3,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.22093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40537849","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: 6

Calcium channel blockade attenuates abnormal synaptic transmission in the dentate gyrus elicited by entorhinal amyloidopathy. 钙通道阻断可减弱由内嗅淀粉样变性引起的齿状回异常突触传递。

IF 2.3

Synapse (New York, N.y.) Pub Date : 2016-10-01 Epub Date: 2016-07-07 DOI: 10.1002/syn.21915

Hamid Gholami Pourbadie, Nima Naderi, Mahyar Janahmadi, Nasrin Mehranfard, Fereshteh Motamedi

{"title":"Calcium channel blockade attenuates abnormal synaptic transmission in the dentate gyrus elicited by entorhinal amyloidopathy.","authors":"Hamid Gholami Pourbadie, Nima Naderi, Mahyar Janahmadi, Nasrin Mehranfard, Fereshteh Motamedi","doi":"10.1002/syn.21915","DOIUrl":"https://doi.org/10.1002/syn.21915","url":null,"abstract":"Entorhinal-hippocampal network is one of the earliest circuits which is affected by Alzheimer's disease (AD). There are numerous data providing the evidence of synaptic deficit in the dentate gyrus (DG) of AD animal model. However, there is little known about how entorhinal cortex (EC) amyloidophaty affects each excitatory and/or inhibitory transmission in the early stage of AD. On the other hand, it is believed that calcium dyshomeostasis has a critical role in the etiology of AD. Here, the effect of the EC amyloid pathogenesis on excitatory or inhibitory post synaptic currents (EPSC and IPSC, respectively) in the DG granule cells and then the possible neuroprotective action of L-type calcium channel blockers (CCBs), nimodipine and isradipine, were examined. The amyloid beta (Aβ) 1-42 was injected bilaterally into the EC of male rats and one week later, synaptic currents in the DG granule cells were assessed by whole cell patch clamp. EPSCs were evoked by stimulating the perforant pathway. Voltage clamp recording showed profound decrease of evoked EPSC amplitude and paired pulse facilitation in the DG granule cells of Aβ treated rats. Furthermore, AMPA/NMDA ratio was significantly decreased in the Aβ treated animals. On the other hand, amplitude of IPSC currents was significantly increased in the DG granule cells of these animals. These modifications of synaptic currents were partially reversed by daily intracerebroventricular administration of isradipine or nimodipine. In conclusion, our results suggest that Aβ in the EC triggers decreased excitatory transmission in the DG with substantial decrement in AMPA currents, leading to a prominent activity of inhibitory circuits and increased inhibition of granule cells which may contribute to the development of AD-related neurological deficits in AD and treatment by CCBs could preserve normal synaptic transmission against Aβ toxicity.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"408-17"},"PeriodicalIF":2.3,"publicationDate":"2016-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21915","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34530668","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: 15

Post-cocaine changes in regulator of G-protein signaling (RGS) proteins in the dorsal striatum: Relevance for cocaine-seeking and protein kinase C-mediated phosphorylation. 可卡因后背纹状体g蛋白信号(RGS)调节蛋白的变化:可卡因寻求和蛋白激酶c介导的磷酸化的相关性。

IF 2.3

Synapse (New York, N.y.) Pub Date : 2016-10-01 Epub Date: 2016-06-21 DOI: 10.1002/syn.21917

Jenna Bilodeau, Marek Schwendt

{"title":"Post-cocaine changes in regulator of G-protein signaling (RGS) proteins in the dorsal striatum: Relevance for cocaine-seeking and protein kinase C-mediated phosphorylation.","authors":"Jenna Bilodeau, Marek Schwendt","doi":"10.1002/syn.21917","DOIUrl":"https://doi.org/10.1002/syn.21917","url":null,"abstract":"Persistent cocaine-induced neuroadaptations within the cortico-striatal circuitry might be related to elevated risk of relapse observed in human addicts even after months or years of drug-free abstinence. Identification of these neuroadaptations may lead development of novel, neurobiologically-based treatments of relapse. In the current study, 12 adult male Sprague-Dawley rats self-administered cocaine (or received yoked-saline) for two weeks followed by three weeks of home-cage abstinence. At this point, we analyzed expression of proteins involved in regulation of Gαi- and Gαq-protein signaling in the dorsal striatum (dSTR). Animals abstinent from chronic cocaine showed decreased expression of regulator of G-protein signaling 2 (RGS2) and RGS4, as well as upregulation of RGS9. These data, together with the increased ratio of Gαq-to-Gαi proteins indicated, \"sensitized\" Gαq signaling in the dSTR of abstinent cocaine animals. To evaluate activation of Gαq signaling during relapse, another group of abstinent cocaine animals (and yoked saline controls, 22 rats together) was reintroduced to the cocaine context and PKC-mediated phosphorylation in the dSTR was analyzed. Re-exposure to the cocaine context triggered cocaine seeking and increase in phosphorylation of cellular PKC substrates, including phospho-ERK and phospho-CREB. In conclusion, this study demonstrates persistent dysregulation of RGS proteins in the dSTR of abstinent cocaine animals that may produce an imbalance in local Gαq-to-Gαi signaling. This imbalance might be related to augmented PKC-mediated phosphorylation during relapse to cocaine-seeking. Future studies will address whether selective targeting of RGS proteins in the dSTR can be utilized to suppress PKC-mediated phosphorylation and relapse to cocaine-seeking.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"432-40"},"PeriodicalIF":2.3,"publicationDate":"2016-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.21917","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34611451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5