Neuropharmacology最新文献_第5页

Evaluating the neuroprotective effects of the novel Kv2.1 blocker Zj7923 against ischemic stroke in vitro and in vivo 评估新型Kv2.1阻滞剂Zj7923对缺血性脑卒中的神经保护作用

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-05-29 DOI: 10.1016/j.neuropharm.2025.110537

Tianjiao Yang, Weiping Wang, Zhuo Li, Jie Cai, Nan Feng, Shaofeng Xu, Ling Wang, Xiaoliang Wang

{"title":"Evaluating the neuroprotective effects of the novel Kv2.1 blocker Zj7923 against ischemic stroke in vitro and in vivo","authors":"Tianjiao Yang, Weiping Wang, Zhuo Li, Jie Cai, Nan Feng, Shaofeng Xu, Ling Wang, Xiaoliang Wang","doi":"10.1016/j.neuropharm.2025.110537","DOIUrl":"10.1016/j.neuropharm.2025.110537","url":null,"abstract":"<div><div>The voltage-dependent potassium channel Kv2.1 correlates closely to the regulation of neuronal excitability and cellular apoptosis. Ischemia or oxidative treatment were known to stimulate the surge of Kv2.1-mediated current to activate neuronal apoptosis pathways, while inhibiting excessive Kv2.1 K<sup>+</sup> current efflux could reduce neuronal apoptosis and exhibit neuroprotective effects. Here, we found a novel Kv2.1 selective blocker Zj7923 and investigated whether it produces neuroprotective function after ischemic stroke animal model. We demonstrate that Zj7923 potently inhibits Kv2.1 current with an IC<sub>50</sub> of 0.12 μM. Zj7923 had no obvious effect on the activation process of Kv2.1 channels, but could significantly accelerate the inactivation process of Kv2.1 channels. The mutations at Y380 and K356 in the outer vestibule of Kv2.1 channels weakened the inhibitory effect of Zj7923, and the IC<sub>50</sub> value of Zj7923 on the mutation channels increased to 3.66 μM and 3.20 μM, respectively, indicating that the compound may act on the above two positions. Zj7923 could increase the spontaneous firing rate of normal hippocampal pyramidal neurons and ameliorate OGD-induced impairment of neuronal excitability. Kv2.1 channel inhibition by Zj7923 provides protection against DTDP-induced apoptosis and its mechanism might be related to the modulation of the expression of apoptosis-related proteins, such as Bcl-2, Bax and cleaved caspase-3 proteins. <em>In vivo</em> pharmacodynamics evaluation, intravenous administration of Zj7923 in rats following transient middle cerebral artery occlusion significantly reduced infarct volume and improved neurological deficits. Our results indicate that Zj7923 exerts a neuronal protection from cerebral ischemia <em>in vitro</em> and <em>in vivo</em> by inhibiting Kv2.1 current and validate the potential value of developing drugs targeting Kv2.1 for ischemic stroke.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110537"},"PeriodicalIF":4.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FGF21 alleviates α-II-spectrin breakdown in a model of oxygen-glucose deprivation and modulates global protein phosphorylation in hippocampal neurons FGF21减轻氧-糖剥夺模型中α-II-Spectrin的破坏并调节海马神经元的全局蛋白磷酸化

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-05-28 DOI: 10.1016/j.neuropharm.2025.110529

Kiersten Gorse , Kara Snyder , Travis C. Jackson

{"title":"FGF21 alleviates α-II-spectrin breakdown in a model of oxygen-glucose deprivation and modulates global protein phosphorylation in hippocampal neurons","authors":"Kiersten Gorse , Kara Snyder , Travis C. Jackson","doi":"10.1016/j.neuropharm.2025.110529","DOIUrl":"10.1016/j.neuropharm.2025.110529","url":null,"abstract":"<div><div>Fibroblast growth factor 21 (FGF21) is a pleiotropic hormone that promotes hippocampal neuroprotection in animal models of ischemic brain injury, but how it works is unclear. In the first experiment we subjected isolated hippocampal neurons to oxygen-glucose deprivation (OGD) injury to test if FGF21 induced neuroprotection is mediated by its direct effects on neurons. Further, because cold stress regulates FGF21 levels in animals, we also explored if post-insult temperature (37 °C versus 33.5 °C) modified FGF21 induced neuroprotection. Experiment 1 revealed that FGF21 treatment at 37 °C decreased α-II-spectrin breakdown product-145 (SBDP-145) levels but did not affect 24 h cell survival. Intraischemic therapeutic hypothermia (TH) decreased SBDP-145 levels and increased 24 h cell survival. Co-treatment with FGF21+TH augmented the effect of cooling to increase the levels of the cold-shock proteins (CSPs) RNA-binding motif 3 (RBM3) and cold-induced RNA-binding protein (CIRBP), without further effecting survival. In Experiment 2, to obtain additional insights on FGF21 signaling responses in neurons, we measured the global phosphoproteome in hippocampal neurons after a 30 min pulse treatment with FGF21, both in normothermic cells and in cells that were subjected to hypothermia for 48 h. This revealed a reprogramming effect of temperature on FGF21 signaling responses. We also identified myristoylated alanine-rich c-kinase substrate-like protein 1 (MARCKSL1) as a novel FGF21 target. In follow-up studies in the OGD model, FGF21 treatment prevented injury induced decreases in MARCKSL1 protein levels. We conclude that FGF21 has a direct inhibitory effect on α-II-spectrin breakdown and modifies neuronal signaling responses in a temperature dependent manner in hippocampal neurons.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110529"},"PeriodicalIF":4.6,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The neuroprotective effects of N-acetylcysteine in psychiatric and neurodegenerative disorders: From modulation of glutamatergic transmission to restoration of synaptic plasticity n -乙酰半胱氨酸在精神和神经退行性疾病中的神经保护作用：从谷氨酸传递的调节到突触可塑性的恢复。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-05-23 DOI: 10.1016/j.neuropharm.2025.110527

Suwarna Chakraborty , B.S. Shankaranarayana Rao, Sunil Jamuna Tripathi

{"title":"The neuroprotective effects of N-acetylcysteine in psychiatric and neurodegenerative disorders: From modulation of glutamatergic transmission to restoration of synaptic plasticity","authors":"Suwarna Chakraborty , B.S. Shankaranarayana Rao, Sunil Jamuna Tripathi","doi":"10.1016/j.neuropharm.2025.110527","DOIUrl":"10.1016/j.neuropharm.2025.110527","url":null,"abstract":"<div><div>N-acetylcysteine (NAC) is an effective pleiotropic drug with a strong safety profile. It is predominantly used as a mucolytic agent and in the treatment of paracetamol overdose. However, extensive research in the last decade has shown the prominent efficacy of NAC in many neuropsychiatric and neurodegenerative disorders. NAC acts through multiple mechanisms; primarily, it releases cysteine and modulates glutamatergic and monoaminergic transmission. Further, it restores glutathione levels, promotes oxidative balance, reverses decreased synaptic plasticity, reduces neuroinflammation and mitochondrial dysfunction, and provides neurotrophic support. Additionally, it regulates one-carbon metabolism pathways, leading to the production of key metabolites. In this review, we will be discussing in-depth mechanisms of action of NAC and its promising ability to reverse neuropathological changes, cognitive deficits and associated plasticity changes in various psychiatric and neurodegenerative diseases, including depression, bipolar disorders, schizophrenia, Alzheimer's disease, Huntington's disease, traumatic brain injury, aging. Overall, several preclinical studies and clinical trials have demonstrated the efficacy of NAC in reversing regressive plasticity, cognitive deficits, and associated changes in the brain. NAC remains among the strongest candidates with a high safety profile for managing several types of neurological disorders.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110527"},"PeriodicalIF":4.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The novel compound CP-10 suppresses microglia-mediated neuroinflammation and neutrophil chemotaxis and attenuates ischemic brain injury by targeting FPR1 新型化合物CP-10通过靶向FPR1抑制小胶质细胞介导的神经炎症和中性粒细胞趋化，减轻缺血性脑损伤

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-05-23 DOI: 10.1016/j.neuropharm.2025.110528

Meng-qi Dong , Yan Chen , Qing Wang , Hui-qin Li , Ling-yun Bai , Xiang Cao , Yun Xu

{"title":"The novel compound CP-10 suppresses microglia-mediated neuroinflammation and neutrophil chemotaxis and attenuates ischemic brain injury by targeting FPR1","authors":"Meng-qi Dong , Yan Chen , Qing Wang , Hui-qin Li , Ling-yun Bai , Xiang Cao , Yun Xu","doi":"10.1016/j.neuropharm.2025.110528","DOIUrl":"10.1016/j.neuropharm.2025.110528","url":null,"abstract":"<div><div>Ischemic stroke represents a major neurological disorder characterized by significant morbidity, where neuroinflammation plays a central role in exacerbating cerebral injury. Following ischemic events, microglial activation and the subsequent infiltration of peripheral immune cells, particularly neutrophils, contribute to the disruption of the blood-brain barrier and amplify neuronal damage. In the present study, as a part of our ongoing screening experiment to evaluate the anti-inflammatory effects of new compounds, a novel compound, namely N-{2-[(7-chloro-4-oxo-4H-pyrido[1,2-a] pyrimidin-2-yl) methoxy] phenyl}-2,2-dimethylpropanamide (referred to as CP-10 in this study), to test whether it could target microglial activation and neutrophil chemotaxis, both critical contributors to ischemic brain injury. CP-10 exhibited no apparent cytotoxicity to primary microglia or neurons at concentrations up to 30 μM. Transcriptomic analysis revealed that CP-10 modulated a wide range of inflammatory and immune response genes, particularly those associated with neutrophil chemotaxis, such as Cxcl1, Cxcl2, Cxcl3, and Cxcl5. Mechanistically, CP-10 exerted its effects by interacting with formyl peptide receptor 1 (FPR1), a receptor involved in microglial activation and neutrophil recruitment. In vivo, CP-10 significantly reduced infarct volume and neurological deficits in a mouse model of middle cerebral artery occlusion (MCAO), accompanied by reduced neutrophil infiltration and microglial activation in the ischemic penumbra. Furthermore, CP-10 inhibited key inflammatory signaling pathways, including NF-κB and MAPK, downstream of FPR1 activation. These findings position CP-10 as a promising candidate for ischemic stroke therapy, targeting neuroinflammation and immune cell chemotaxis via FPR1 modulation.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"277 ","pages":"Article 110528"},"PeriodicalIF":4.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144139424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dimercaprol attenuates oxidative stress-induced damage of retinal ganglion cells in an in vitro and in vivo model of traumatic optic neuropathy 在体外和体内创伤性视神经病变模型中，二巯基醇可减轻氧化应激诱导的视网膜神经节细胞损伤。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-05-21 DOI: 10.1016/j.neuropharm.2025.110525

Xiangpeng Tan , Meiting Han , Mengke Han , Shuo Ren , Yue Sun , Xiaoqing Zeng , Xin Liu , Lin Yan , Abekah Gabriel , Qingqing Yao , Dulin Kong , Xiaohui Wang , Jianzhang Wu , Wencan Wu

{"title":"Dimercaprol attenuates oxidative stress-induced damage of retinal ganglion cells in an in vitro and in vivo model of traumatic optic neuropathy","authors":"Xiangpeng Tan , Meiting Han , Mengke Han , Shuo Ren , Yue Sun , Xiaoqing Zeng , Xin Liu , Lin Yan , Abekah Gabriel , Qingqing Yao , Dulin Kong , Xiaohui Wang , Jianzhang Wu , Wencan Wu","doi":"10.1016/j.neuropharm.2025.110525","DOIUrl":"10.1016/j.neuropharm.2025.110525","url":null,"abstract":"<div><div>Traumatic optic neuropathy (TON) is a prevalent form of optic neuropathy, which is a significant cause of irreversible blindness. To date, effective therapeutic interventions for TON are lacking, highlighting the urgent need for the development of new therapeutic drugs. In this study, a compound library comprising 480 Food and Drug Administration (FDA)-approved drugs was screened to identify potentially effective therapeutic drugs for TON. We reported that dimercaprol (DMP), an FDA-approved drug, can reduce L-Glutamic acid (Glu) and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-induced injury in a retinal cell line (R28 cell). Our findings further demonstrated that intracellular reactive oxygen species (ROS) and acrolein, a lipid peroxide, are major contributors to apoptosis-induced cell death <em>in vitro</em>. A series of functional assays revealed that DMP can inhibit apoptosis-induced by Glu via scavenging of intracellular ROS and acrolein in R28 cells and primary cortical neurones. Notably, DMP inhibited retinal ganglion cell complex (GCC) thinning and retinal ganglion cell (RGC) loss resulting from optic nerve crush (ONC) injury <em>in vivo</em>. Moreover, DMP effectively eliminated ONC-induced acrolein in the retina and inhibited RGC apoptosis <em>in vivo</em>. In conclusion, intracellular ROS and acrolein play significant roles in RGC loss in TON, and DMP effectively inhibits RGC apoptosis-induced by the oxidative stress pathway <em>in vitro</em> and <em>in vivo</em>. Therefore, DMP has emerged as a potential new therapeutic drug against TON.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"277 ","pages":"Article 110525"},"PeriodicalIF":4.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Low-dose cannabidiol treatment prevents chronic stress-induced phenotypes and is associated with multiple synaptic changes across various brain regions 低剂量大麻二酚治疗可预防慢性应激诱导的表型，并与大脑不同区域的多个突触变化有关。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-05-21 DOI: 10.1016/j.neuropharm.2025.110526

Sara Borràs-Pernas , Anna Sancho-Balsells , Lisa Patterer , Maoyu Wang , Daniel del Toro , Jordi Alberch , Daniele Schibano , Joan Espel , Maya Heybeck , Bernhard Scheidel , Albert Giralt

{"title":"Low-dose cannabidiol treatment prevents chronic stress-induced phenotypes and is associated with multiple synaptic changes across various brain regions","authors":"Sara Borràs-Pernas , Anna Sancho-Balsells , Lisa Patterer , Maoyu Wang , Daniel del Toro , Jordi Alberch , Daniele Schibano , Joan Espel , Maya Heybeck , Bernhard Scheidel , Albert Giralt","doi":"10.1016/j.neuropharm.2025.110526","DOIUrl":"10.1016/j.neuropharm.2025.110526","url":null,"abstract":"<div><div>Major Depressive Disorder (MDD) is a heterogeneous and debilitating mood disorder often associated with stress. Although current treatments are available, they remain ineffective for approximately 30 % of affected individuals and are frequently accompanied by undesirable side effects. Cannabidiol (CBD) has emerged as a potential and safe therapeutic option for alleviating depressive symptoms; however, the underlying molecular mechanisms through which this compound exerts its beneficial effects are not yet fully understood. In this study, we demonstrate that a very low dose of CBD (1 mg/kg) can partially reverse some sequelae induced by chronic stress, a well-established mouse model used to simulate depressive-like symptoms. Using mass spectrometry to analyze different brain regions, we observed several improvements following CBD treatment, particularly in the medial prefrontal cortex (mPFC), across multiple neurotransmission systems (including glutamatergic and serotonergic pathways). Microstructural experiments, utilizing double-labeling of F-Actin and VGlut1-positive clusters, revealed a complete restoration of mature synapses in the mPFC of mice treated with CBD. In conclusion, our findings indicate that a very low dose of CBD is effective in counteracting the adverse effects of chronic stress, possibly through the synaptic remodeling of excitatory synapses in the mPFC.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"277 ","pages":"Article 110526"},"PeriodicalIF":4.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of inhibiting the orexin system on nicotine reward memory and fear memory 抑制食欲素系统对尼古丁奖励记忆和恐惧记忆的影响

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-05-19 DOI: 10.1016/j.neuropharm.2025.110523

Pan Cui , Danping Wu , Jing Dong , Yun Chen , Jialu Feng , Xiaoliu Liu , Zuxin Chen , Jing Ge , Jianfeng Liu

{"title":"Effects of inhibiting the orexin system on nicotine reward memory and fear memory","authors":"Pan Cui , Danping Wu , Jing Dong , Yun Chen , Jialu Feng , Xiaoliu Liu , Zuxin Chen , Jing Ge , Jianfeng Liu","doi":"10.1016/j.neuropharm.2025.110523","DOIUrl":"10.1016/j.neuropharm.2025.110523","url":null,"abstract":"<div><div>The orexin system is associated with various brain functions, including reward processing and the stress response. Previous studies have suggested that orexin receptors (OXRs) antagonists could be beneficial in treating several mental disorders, such as drug addiction and post-traumatic stress disorder. However, the specific role of the orexin system in both appetitive (reward-related) and aversive (fear-related) memories remains unclear. In this study, we used nicotine-induced conditioned place preference (CPP) and fear conditioning models to evaluate the effects of suvorexant, a dual OXRs antagonist, and chemogenetic inhibition of orexin neurons in the lateral hypothalamus (LHA) on the retrieval, reconsolidation, and/or extinction of both nicotine reward memory and fear memory. Our findings indicated that suvorexant impaired the expression of nicotine CPP in a dose-dependent manner. These behavioral results aligned with neurochemical evidence from cFos staining, which showed activation of the LHA and orexin neurons in the LHA following the expression of nicotine CPP. Furthermore, using orexin-cre rats, we found that chemogenetic inhibition of orexin neurons in the LHA also reduced the expression of nicotine CPP. However, neither of these interventions affected the reconsolidation of nicotine reward memory. Moreover, neither suvorexant nor the chemogenetic inhibition of LHA orexin neurons affected the retrieval, reconsolidation, or extinction of fear memory, or anxiety-like behaviors, as evaluated by elevated plus maze and open field tests. In summary, our data suggest that the orexin system plays a crucial role in retrieving nicotine reward memory, and suggest that suvorexant may be a promising pharmacotherapy for treating nicotine addiction.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"276 ","pages":"Article 110523"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144098625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dopamine D1 receptors in the medial prefrontal cortex and basolateral amygdala cooperatively contribute to social defeat stress-induced augmentation of cocaine reward in mice 内侧前额叶皮层和杏仁核基底外侧多巴胺D1受体共同参与社会失败应激诱导的小鼠可卡因奖励增强

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-05-19 DOI: 10.1016/j.neuropharm.2025.110524

Atsushi Saito , Hirohito Esaki , Haruka Murata, Xiyan Ni, Naoya Nishitani, Satoshi Deyama, Katsuyuki Kaneda

{"title":"Dopamine D1 receptors in the medial prefrontal cortex and basolateral amygdala cooperatively contribute to social defeat stress-induced augmentation of cocaine reward in mice","authors":"Atsushi Saito , Hirohito Esaki , Haruka Murata, Xiyan Ni, Naoya Nishitani, Satoshi Deyama, Katsuyuki Kaneda","doi":"10.1016/j.neuropharm.2025.110524","DOIUrl":"10.1016/j.neuropharm.2025.110524","url":null,"abstract":"<div><div>Stress potentiates the rewarding effects of cocaine; however, its underlying mechanism remains unclear. Here, we investigated the role of dopaminergic transmission in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA), key brain regions implicated in addiction and stress responses, using the cocaine conditioned place preference (CPP) paradigm combined with acute social defeat (SD) stress in male mice. SD stress exposed immediately before the posttest augmented cocaine CPP, which was significantly reduced by systemic injection of SCH23390, a dopamine D<sub>1</sub> receptor antagonist. Fiber photometry recordings using a GRAB<sub>DA</sub> sensor revealed SD stress-induced elevations in extracellular dopamine levels in both the mPFC and BLA. Accordingly, bilateral intra-mPFC or bilateral intra-BLA injections of SCH23390 suppressed the stress-induced augmentation of cocaine CPP. Additionally, functional disconnection, achieved via unilateral intra-mPFC SCH23390 injection combined with contralateral intra-BLA SCH23390 injection, suppressed stress-induced CPP augmentation. Moreover, unilateral intra-mPFC SCH23390 injection combined with contralateral intra-BLA injection of NBQX, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, inhibited the augmented CPP. Furthermore, selective chemogenetic silencing of glutamatergic projections from the mPFC to the BLA suppressed augmented cocaine CPP. These findings suggest that bilateral and simultaneous D<sub>1</sub> receptor-mediated dopaminergic inputs to the mPFC and BLA, as well as the subsequent facilitation of glutamatergic transmission from the mPFC to the BLA, play a crucial role in the SD stress-induced potentiation of the rewarding effects of cocaine.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"276 ","pages":"Article 110524"},"PeriodicalIF":4.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to “The novel miR_146-Tfdp2 axis antagonizes METH induced neuron apoptosis and cell cycle abnormalities in tree shrew” [Neuropharmacology (2025 Apr 1) 267, 110300] “新型miR_146-Tfdp2轴拮抗甲基安非他明诱导的树鼩神经元凋亡和细胞周期异常”[神经药理学（2025 Apr 1） 267, 110300]的更正。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-05-17 DOI: 10.1016/j.neuropharm.2025.110510

Shuwei Zhang , Chan Wang , Jianxing Liu , Liu Liu , Lin Miao , Haowei Wang , Yunqing Tian , Hao Cheng , Juan Li , Xiaofeng Zeng

引用次数: 0

Repeated alcohol drinking in mice is associated with bidirectional alterations in corticostriatal coherence 小鼠反复饮酒与皮质纹状体一致性的双向改变有关。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-05-17 DOI: 10.1016/j.neuropharm.2025.110522

Cherish E. Ardinger , Mitchell D. Morningstar , Christopher C. Lapish , David N. Linsenbardt

{"title":"Repeated alcohol drinking in mice is associated with bidirectional alterations in corticostriatal coherence","authors":"Cherish E. Ardinger , Mitchell D. Morningstar , Christopher C. Lapish , David N. Linsenbardt","doi":"10.1016/j.neuropharm.2025.110522","DOIUrl":"10.1016/j.neuropharm.2025.110522","url":null,"abstract":"<div><div>Decreased functional connectivity between the striatum and frontal cortex is observed in individuals with alcohol use disorder (AUD), and predicts the probability of relapse in abstinent individuals with AUD. To further our understanding of how repeated alcohol consumption impacts the corticostriatal circuit, extracellular electrophysiological recordings (local field potentials; LFPs) were gathered from the nucleus accumbens (NAc) and prefrontal cortex (PFC) of C57BL/6J mice voluntarily consuming alcohol or water using the 2-h access ‘drinking-in-the-dark’ (DID) procedure. Following a three-day acclimation period wherein only water access was provided during DID, mice were given 14 consecutive days of access to alcohol. Electrophysiology data was collected throughout the entirety of the final day of acclimation (i.e. water baseline) and the first and final days of alcohol access. We evaluated power and coherence at five frequency bands during bouts of drinking. Surprisingly, we only detected significant changes in power in the NAc; no differences were observed in power in the PFC. Increases in NAc power were detected at the Theta, Beta, and Gamma frequencies. At each of these frequencies, increases were identified on the final alcohol session compared to water baseline. Only at the Theta frequency were increases also detected compared to the first alcohol session. Furthermore, significant <em>increases</em> in Delta coherence were observed on the final alcohol session compared to water baseline, whereas significant <em>decreases</em> in Theta and Beta coherence were identified on both alcohol sessions compared to water baseline. These results provide additional support for alterations in the functional coupling of corticostriatal circuits associated with alcohol consumption and suggest the Theta frequency may be uniquely susceptible to these alterations.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"277 ","pages":"Article 110522"},"PeriodicalIF":4.6,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0