NEUROPHARMACOLOGY神经药理学
NEUROPHARMACOLOGY(英文缩写 NEUROPHARMACOLOGY),ISSN 0028-3908,eISSN 1873-7064,中文译名:神经药理学 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-11-01 至 2026-10-31，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 5.273 | Q1 |
| 2022 | 4.700 | Q1 |
| 2023 | 4.600 | Q1 |
| 2024 | 4.600 | Q1 |
| 2025 | 4.700 | Q1 |
NEUROPHARMACOLOGY 最新收录文献
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1. Profiling the effects of alcohol history on cognitive performance during abstinence: an examination of proenkephalin-A-derived peptides in the medial prefrontal cortex.
1. 分析饮酒史对戒酒期间认知表现的影响：内侧前额叶皮层中前脑啡肽-A衍生肽的考察PMID:日期:2026-10-01Cognitive impairments during abstinence may complicate recovery from alcohol use disorder, but their persistence across executive domains and accompanying cortical adaptations remain unclear. Neuropeptides are candidate mediators of persistent alcohol (ethanol; EtOH) effects, and emerging evidence implicates endogenous opioid peptides in cortical processing. Here, we examined cognitive function and medial prefrontal cortex (mPFC) enkephalin profiles in rats with a history of chronic EtOH exposure. Using a longitudinal operant-based approach, we assessed cognitive flexibility during early abstinence and delay-dependent working memory during protracted abstinence. We then quantified methionine-enkephalin (Met-ENK) and leucine-enkephalin (Leu-ENK) and profiled the proenkephalin-A (PENK)-derived peptide pool in the mPFC. EtOH history did not alter overall trials or errors to criterion during strategy set-shifting or reversal learning. During reversal, however, EtOH rats showed greater perseverative bias, with response adjustments less aligned with recent feedback and more strongly influenced by prior reinforcement. During initial testing at the longest working memory delay, EtOH rats also showed lower accuracy. Performance across these tasks was correlated in EtOH rats, suggesting individual differences in cognitive susceptibility were maintained across abstinence. Targeted analyses showed comparable levels of Met-ENK and Leu-ENK between groups. Although individual PENK-derived sequences did not differ in abundance, compositional analysis showed a greater summed relative contribution of C-terminal fragments in EtOH samples. These findings indicate that EtOH history produces lasting cognitive vulnerabilities that emerge under greater task demands, with some animals remaining more susceptible than others. C-terminal PENK profiling may reveal novel targets associated with enduring mPFC adaptations during abstinence.
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2. Adolescent Ethanol Exposure Reduces Central Amygdala GABA Transmission But Preserves Noradrenergic Signaling In Adulthood.
2. 青少年期乙醇暴露会降低成年期中央杏仁核GABA传递，但保留去甲肾上腺素能信号传导PMID:日期:2026-09-29Early initiation of alcohol use is a risk factor for developing alcohol use disorder (AUD) later in life, yet the long-term neuronal consequences of adolescent drinking remain poorly understood. The central amygdala (CeA) drives the negative emotional states that promote excessive drinking, and its overactivation is a hallmark of AUD in adults. Moreover, alcohol releases the stress signal norepinephrine (NE) into the adult CeA, leading to sex-dependent changes in its GABA transmission. Whether similar alcohol-induced changes in the adolescent CeA contribute to later-life vulnerability to AUD is unknown. In the present study, we used an intragastric gavage model of adolescent intermittent ethanol (AIE) exposure in Sprague-Dawley rats to examine the long-lasting effects on CeA synapses and noradrenergic regulation. AIE reduced basal GABA transmission via pre- and postsynaptic mechanisms in adults of both sexes, a response that deviates from the typical increased inhibition found in subjects only exposed to ethanol during adulthood. We observed similar NE-induced increases in CeA GABA release in adult males and females regardless of AIE exposure, and no differences were observed in CeA adrenergic receptor gene expression. Collectively, our data reveal that AIE produced a long-lasting reduction in adult CeA inhibitory tone, and this change is likely independent of the noradrenergic system. This developmental-specific shift in CeA activity reflects the heightened vulnerability of the adolescent brain to ethanol-induced neuroadaptation and may represent a neural substrate underlying the increased risk of AUD following adolescent alcohol use.
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3. {"_":"STEP is a regulator of mGluR5 expression.","sub":["61"]}
3. {"_":"STEP是mGluR5表达的调节因子。","sub":["61"]}PMID:日期:2026-09-28Metabotropic glutamate receptor 5 (mGluR5) is a Gq protein-coupled receptor that modulates both excitatory and inhibitory neurotransmission and regulates numerous higher-order neural processes ranging from learning and memory to mood and behavior. Trafficking of mGluR5 to the plasma membrane is critical for its biological functions and phosphorylation is an important regulator of mGluR5 trafficking and function. We previously reported that striatal-enriched protein tyrosine phosphatase 61 (STEP) interacts with mGluR5 in a proteomics study of the STEP interactome. Here, we explored the relationship between STEP and mGluR5 in greater detail and find that STEP, like mGluR5, is preferentially localized to extra-synaptic sites in neurons using electron microscopy. A systematic evaluation of STEP in heterologous cells identifies its kinase-interacting and amino-terminal domains as being important for mGluR5 binding. Interestingly, we find that STEP decreases mGluR5 surface and total protein levels in both heterologous cells and neurons in a lysosome-dependent manner. Conversely, mGluR5 protein and tyrosine phosphorylation levels are increased in STEP knockout (KO) mouse brain. There are four tyrosine residues in the cytosolic tail region of mGluR5, and their mutation decreases total and surface receptor protein levels. Together, these findings reveal an important role of STEP-mediated tyrosine dephosphorylation as a negative regulator of mGluR5 surface protein levels and stability.
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4. Tactile stimulation modulates withdrawal-related behaviors and brain molecular parameters in male offspring following perinatal morphine exposure.
4. 触觉刺激调节围产期吗啡暴露后雄性后代戒断相关行为及脑分子参数PMID:日期:2026-09-28The opioid crisis has intensified over recent decades, largely driven by the widespread and often indiscriminate prescription of opioid analgesics for chronic pain, leading to an unprecedented global burden of opioid-related morbidity and mortality. In this context, maternal opioid use represents a critical source of neurodevelopmental vulnerability for exposed offspring, irrespective of the occurrence of neonatal withdrawal, which develops in only a subset of opioid-exposed infants. This highlights the urgent need to elucidate the neurobiological mechanisms of dependence at birth and to identify early interventions capable of mitigating withdrawal and preventing long-term consequences. By promoting neuroplasticity, tactile stimulation (TS) represents a promising early-life intervention for recovery from withdrawal-related symptoms and dysfunctions after early opioid exposure. To investigate this, pregnant rats received escalating doses of morphine throughout gestation and lactation, while male offspring were exposed to early-life TS until weaning, followed by behavioral assessment of withdrawal-related responses. Moreover, molecular analyses of addiction- and neuroplasticity-related markers in brain reward and hedonic circuits were performed. Maternal exposure to morphine increased withdrawal-related behavioral responses in the offspring, whereas early-life TS effectively attenuated these alterations, restoring the overall withdrawal behavioral profile. At the molecular level, perinatal morphine disrupted dopaminergic and glutamatergic signaling in the Nucleus accumbens, as evidenced by the modulation of D1-R, D2-R, GLUA1-R, DAT and ΔFosB levels. Notably, TS reversed these neurochemical alterations, restoring molecular marker levels toward baseline values. Together, these findings support TS as a non-invasive intervention with the potential to mitigate neonatal abstinence syndrome, modulate addiction-related neuroplasticity, and support neurodevelopment in infants exposed to opioids during early life.
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5. Proteasome-dependent degradation of DAPK1 by wogonoside blocks PARthanatos and protects against ischemic stroke.
5. 汉黄芩苷通过蛋白酶体依赖性降解DAPK1阻断PARthanatos并预防缺血性脑卒中PMID:日期:2026-09-26Ischemic stroke remains a leading cause of death and disability, yet effective pharmacological neuroprotection remains elusive. ROS-induced PARthanatos-driven by PARP1 hyperactivation and the mitochondrial-apoptosis-inducing factor (AIF) death axis-is a principal executor of ischemic neuronal death. However, direct PARP1 inhibition inevitably compromises essential DNA repair. Here, we identify a downstream intervention node that uncouples lethal signaling from genomic maintenance. Through phenotype-to-target deconvolution combining reverse pharmacophore mapping, bioinformatic intersection with programmed cell death genes, and integrated biophysical validation (docking, 100-ns molecular dynamics, cellular thermal shift assay, and surface plasmon resonance), we demonstrate that wogonoside (WS), a flavonoid glycoside from Scutellaria baicalensis, directly binds death-associated protein kinase 1 (DAPK1; KD = 6.07 μM) and acts as a ligand-induced degrader that triggers proteasome-dependent DAPK1 clearance. CRISPR/Cas9-mediated DAPK1 knockout fully phenocopied WS-mediated protection, whereas ectopic DAPK1 overexpression abolished it. WS-induced degradation intercepted the JNK-mitochondrial depolarization-AIF nuclear translocation cascade while leaving PARP1 catalytic activity, PAR polymer formation, and γH2AX resolution fully intact-in stark contrast to the clinical PARP1 inhibitor olaparib. In a mouse permanent distal middle cerebral artery occlusion model, a single dose of WS reduced cortical infarct volume by ∼50%, preserved neurons, suppressed microglial activation, and maintained microvascular integrity, accompanied by significant sensorimotor recovery. Single-nucleus RNA sequencing revealed Dapk1 enrichment in activated microglia and co-variation with neuronal MAPK pro-death signaling, suggesting a dual-compartment mechanism. These findings define proteasome-dependent DAPK1 degradation as a mechanistically distinct antioxidant strategy for acute ischemic stroke.
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6. {"_":"Novel allosteric modulation of the human 5-HTA receptor by the clinically used drugs piperazine and hydroxyzine.","sub":["3"]}
6. {"_":"临床使用药物哌嗪和羟嗪对人体5-HTA受体的新型变构调节。","sub":["3"]}PMID:日期:2026-09-25The 5-HT receptor is a serotonin-gated cation channel of the pentameric ligand-gated ion channel family and plays a key role in fast synaptic transmission within the central, peripheral, and enteric nervous systems. Dysregulation of this receptor has been linked to neurological, psychiatric, and gastrointestinal disorders. While competitive 5-HT antagonists, primarily setrons, are clinically used to alleviate gastrointestinal symptoms, there is a growing interest in developing new negative allosteric modulators (NAMs) for this receptor. Here, we applied a drug-repositioning strategy targeting the human 5-HTA receptor. Using macroscopic current recordings, we identified a previously unrecognized NAM activity of two clinically used drugs, piperazine and its derivative hydroxyzine, on the 5-HTA receptor. Computational analyses suggested two distinct binding sites at subunit interfaces: one in the lower extracellular domain and another in the upper transmembrane domain. Functional characterization of receptors carrying mutations at key residues within these sites (E75, E208, S248, D293) showed that some mutations abolished drug-induced inhibition, whereas others enhanced the inhibitory effect of hydroxyzine. Altogether, these results validate the proposed allosteric sites and demonstrate that both contribute to the actions of these compounds. This work uncovers a new functional connection between 5-HTA receptors and piperazine-derived drugs, opening avenues for therapeutic repurposing.
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7. AA-2βG attenuates nigrostriatal degeneration and related dopaminergic, redox, and inflammatory alterations in experimental parkinsonism.
7. AA-2βG减轻实验性帕金森病中黑质纹状体变性及相关的多巴胺能、氧化还原和炎症改变PMID:日期:2026-09-23Parkinson's disease (PD) is characterized by progressive nigrostriatal degeneration, dopamine depletion, and interactions among neuronal vulnerability, oxidative imbalance, and neuroinflammatory responses. AA-2βG is a chemically stable ascorbate derivative; however, its protective profile in experimental parkinsonism remains incompletely defined. We prioritized in vivo phenotyping using a subacute MPTP-induced mouse model, followed by complementary cellular analyses and exploratory transcriptomic profiling. AA-2βG was administered orally at 75, 150, or 300 mg/kg for 17 days, starting 3 days before MPTP administration. Under this pre-exposure paradigm, AA-2βG attenuated body-weight loss and motor deficits, reduced the decline in tyrosine hydroxylase immunoreactivity, and preserved Nissl-positive neuronal populations in the substantia nigra pars compacta. AA-2βG partially preserved striatal dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid levels and attenuated alterations in dopamine turnover indices. AA-2βG attenuated glial activation markers, central and peripheral inflammatory changes, and redox disturbances in MPTP-exposed mice, accompanied by improvements in total antioxidant capacity, antioxidant enzyme activities, and glutathione redox status. Complementary experiments in SH-SY5Y neuroblastoma cells, BV2 microglia, and SVGP12 astrocytes showed selected neuronal injury, inflammatory, and trophic responses associated with the in vivo phenotype. Transcriptomic profiling identified AA-2βG-associated changes involving Drd2, Spp1, Lamp5, and Slc39a10; RT-qPCR and protein analyses supported selected expression changes but did not establish causal mediation. No overt histopathological abnormalities or elevations in serum liver enzymes were observed under the tested regimen. Collectively, these findings show that AA-2βG attenuates MPTP-associated neuronal, neurochemical, redox, glial, and inflammatory alterations and support evaluation in progressive and post-lesion models of parkinsonian neurodegeneration.
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8. Sensor sensibility: Divergent measurements of dopaminergic signaling to acute morphine administration via fiber photometry.
8. 传感器灵敏度：通过光纤光度法对急性吗啡给药后多巴胺能信号传导的差异性测量PMID:日期:2026-09-21Activity of the mesolimbic dopamine system has long been implicated in encoding primary rewards and contributing to the addictive properties of drugs of abuse. Dopamine neurons in the ventral tegmental area (VTA) of the midbrain typically show patterns of spontaneous burst activity that align with the onset of salient events or rewarding stimuli, resulting in phasic dopamine release in the nucleus accumbens (NAc). Fiber photometry is increasingly being used as an accessible technique to quantify neural activity with high temporal resolution at sensors offering signal specificity in stable recordings over extended periods of time. It has been well established by multiple techniques that opioids increase mesolimbic dopamine activity, likely through disinhibition of VTA neurons. Here we used fiber photometry to compare sub-second transient events from VTA neurons with GCaMP6f and dopamine release in the lateral shell of the NAc with dLight1.3b and GRABDA2h in response to morphine treatment. In weekly sessions, one dose of morphine was administered in escalating order (2.5, 5,7.5, and 10 mg/kg, intraperitoneal). Consistent with prior literature, both GCaMP6f in VTA neurons and dLight1.3b in NAc showed patterns of increased signal following morphine treatment. In contrast, morphine suppressed transient activity at GRABDA2h sensors. Further analyses of whole signal streams from each sensor showed a generalized increase, but reduction in variability of the GRABDA2h signal, consistent with the interpretation of sensor saturation. Such results emphasize the importance of the inclusion of appropriate controls to contextualize the interpretation of biosensor responses, particularly in response to pharmacological treatment.
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9. Samm50 downregulation-driven mitochondrial dysfunction triggers ferroptosis and contributes to ketamine-induced neurotoxicity and cognitive impairment.
9. Samm50下调驱动的线粒体功能障碍触发铁死亡并导致氯胺酮诱导的神经毒性和认知障碍PMID:日期:2026-09-18Ketamine abuse is associated with persistent cognitive deficits and neurotoxicity, though the underlying mechanisms remain incompletely understood. While mitochondrial dysfunction and ferroptosis have been separately implicated, their causal relationship and the key molecular link in ketamine-induced hippocampal damage are unclear. Using a mouse model of ketamine-induced cognitive impairment and an HT22 hippocampal neuronal cell line, we found that ketamine significantly downregulated Samm50, a key protein maintaining mitochondrial outer membrane integrity, in both the hippocampus and HT22 cells. This downregulation was accompanied by reduced mitochondrial membrane potential (MMP) and ATP levels, and elevated reactive oxygen species (ROS). Concurrently, ketamine upregulated transferrin receptor TFR1, led to Fe/Fe accumulation, increased malondialdehyde (MDA) and lipid peroxidation (LPO), and decreased the ferroptosis regulators GPX4 and SLC7A11. In vitro, ferroptosis inhibitors Fer-1 and deferoxamine (DFO) reversed ketamine-induced cell death, Fe overload, LPO, and MMP loss, but Fer-1 failed to restore ATP or Samm50 expression. MitoQ rescued ATP, MMP, and ROS. Strikingly, Samm50 overexpression not only restored mitochondrial function (ATP, MMP, ROS) but also upregulated GPX4 and SLC7A11, thereby ameliorating ferroptosis. Collectively, ketamine induces hippocampal neurotoxicity and cognitive impairment via a two-step mechanism: it first downregulates Samm50, leading to primary mitochondrial dysfunction (energy failure and oxidative stress); this mitochondrial impairment then triggers ferroptosis through iron accumulation and suppression of GPX4/SLC7A11. Samm50 downregulation serves as a critical upstream event linking mitochondrial dysfunction to ferroptosis, representing a novel therapeutic target for ketamine-induced neuropsychiatric toxicity.
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10. Corrigendum to "Changes in the hippocampal and peripheral phospholipid profiles are associated with neurodegeneration hallmarks in a long-term global cerebral ischemia model: Attenuation by Linalool" [Neuropharmacology 135 (2018) 555-571].
10. “海马和外周磷脂谱的变化与长期全脑缺血模型中的神经退行性标志物相关：芳樟醇的减轻作用”的勘误 [Neuropharmacology 135 (2018) 555-571]PMID:日期:2026-09-16该文献暂无摘要。