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{"title":"Stress-enhanced fear learning can be reduced with unconditional stimulus deflation with constraints.","authors":"Jaden B Brooks, Payton K Robinson, Sean Warner, Priya Halder, Sydney Trask","doi":"10.1016/j.bbr.2025.115438","DOIUrl":"10.1016/j.bbr.2025.115438","url":null,"abstract":"<p><p>Exposure to extreme stress can negatively impact behavior and lead to prolonged fear sensitization. These processes can be studied in the lab using stress-enhanced fear learning (SEFL), where prior exposure to inescapable stress exacerbates later contextual fear conditioning. A common method to reduce conditional fear is through extinction, where a conditional stimulus once paired with an unconditional (US; e.g., a footshock) is presented alone. Previous research shows that extinction learning may not be as effective at reducing fear behavior in rodents previously exposed to stress, mirroring similar extinction impairments observed in aged rodents. Weak-shock exposure (termed US deflation) following conditioning with a strong shock has been proposed to be an alternative to extinction where presentations of weaker versions of the US would work to modify the original fear memory rather than create a new memory as in extinction and thus more precisely target the original context fear memory. While effective under normal conditions, it has yet to be studied how effective US deflation is at reducing stress-enhanced context fear. Here we aimed to test if US deflation could reduce fear in a SEFL paradigm and identify any constraints of this effect. Following 15 inescapable footshocks or matched chamber exposure, male and female Long Evans rats received 1 context-shock pairing or 5 context-shock pairings in a novel context. The next day, they were given either 10 weak footshocks (US deflation) or extinction before behavioral testing. Following training with 1 context-shock pairing, both US deflation and extinction functioned similarly in reducing freezing behavior of stressed rodents. However, following 5 context-shock pairings, only the unstressed rodents displayed a significant decrease in fear behavior, suggesting that prior stress coupled with more robust conditioning can limit the efficacy of US deflation in reducing fear behavior. Finally, we replicated the SEFL effect in aged rodents and found that they showed a significant decrease in stress-enhanced fear learning following US deflation, whereas our previous research showed impairments of traditional extinction in aged rodents. Together, these results suggest that US deflation can reduce SEFL in both adult and aged rodents following a single context-shock pairing, with additional pairings rendering this procedure ineffective at mitigating the effects of prior stress.</p>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"481 ","pages":"115438"},"PeriodicalIF":2.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treating anxiety comorbidity: Lessons from exposure generalization studies.","authors":"Armin Zlomuzica, Iris Kodzaga, Kayleigh Piovesan, Annalisa Lipp","doi":"10.1016/j.bbr.2024.115409","DOIUrl":"10.1016/j.bbr.2024.115409","url":null,"abstract":"<p><p>Comorbidity is a characteristic hallmark of anxiety disorders. Presence of comorbid anxiety and depression is challenging to the diagnosis and treatment. Conventional and transdiagnostic treatment options for anxiety disorders strongly depend on the use of exposure. Recent compelling evidence suggests that the beneficial effects of exposure therapy are transferable across different fear- and anxiety provoking situations and might even affect depressive symptomatology. We provide an overview of findings on existing studies on generalization of exposure effects to untreated stimuli and depression. Potential mechanisms which contribute to generalization of beneficial exposure therapy effects, such as extinction generalization, mastery-related increases in self-efficacy and underlying neural changes are presented and discussed. Understanding and promoting mechanisms related to exposure therapy efficacy and generalization can expedite and enhance the development of more effective transdiagnostic therapy approaches for comorbid anxiety disorders.</p>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":" ","pages":"115409"},"PeriodicalIF":2.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in sensorimotor integration, cervical sensorimotor control, and cognitive-motor dual tasking costs in chronic non-specific neck pain patients with high vs. low catastrophizing tendencies compared to healthy controls.","authors":"Ibrahim M Moustafa, Amal Ahbouch, Shima Abdollah Mohammad Zadeh, Tamer Shousha, Paul A Oakley, Deed Harrison","doi":"10.1016/j.bbr.2025.115434","DOIUrl":"10.1016/j.bbr.2025.115434","url":null,"abstract":"<p><p>Chronic non-specific neck pain (CNSNP) is a common condition and its relationship to the pain catastrophizing construct in terms of sensorimotor functions and dual task performance is not fully understood. We aimed to investigate the differences in sensorimotor integration, cervical sensorimotor control, and cognitive-motor dual tasking abilities between CNSNP patients (> 3 months) with high versus low catastrophizing tendencies and healthy controls. Ninety participants were recruited, 30 asymptomatic controls, and 60 patients with CNSNP; 30 scoring high (> 75th percentile) and 30 scoring low (< 25th percentile) on the pain catastrophizing scale (PCS). The variables of sensorimotor integration (frontal N30 amplitude), cervical sensorimotor control (head repositioning accuracy (HRA) - left and right), and cognitive-motor dual tasking (percentage of gait speed time increase with a cognitive load) were assessed and compared across groups. In general, performance of sensorimotor integration, cervical sensorimotor control, and cognitive-motor dual tasking abilities was incrementally better comparing the high to low catastrophizing groups, and the low catastrophizing group to the controls. Correlation coefficients between PCS and HRA (left and right) was strong (r = .8, p < 0.001), between PCS and dual tasking cost was moderate (r = .7, p < 0.001), and between PCS and frontal N30 amplitude was moderate (r = .57, p < 0.001). In conclusion, we found that higher pain catastrophizing was associated with poorer sensorimotor integration, cervical sensorimotor control, and cognitive-motor dual tasking in CNSNP patients highlighting the importance of both assessing and treating catastrophizing in the treatment of CNSNP. PERSPECTIVE: This study highlights the significant impact of pain catastrophizing on sensorimotor integration, cervical sensorimotor control, and cognitive-motor dual tasking in CNSNP patients. High catastrophizers are particularly vulnerable to these impairments, suggesting the need for comprehensive treatment approaches that address both psychological as well as physical components.</p>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"481 ","pages":"115434"},"PeriodicalIF":2.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overcoming barriers in global neurological care: A call for innovation and policy change.","authors":"M Z Ihsan, Dony Apriatama, Pithriani, Riza Amalia","doi":"10.1016/j.jns.2024.123375","DOIUrl":"10.1016/j.jns.2024.123375","url":null,"abstract":"","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"469 ","pages":"123375"},"PeriodicalIF":3.6,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel peptide CP29L, selected from the phage displayed cyclic random heptapeptide library, demonstrates its potent inhibitory effects to liver cancer HCCLM3 cells by targeting FOXM1.","authors":"Xinyi Hua, Kun Xiang, Anping Liang, Miao Chang, Shijie Jia, Zhixian Shang, Yuhong Jiang, Xinrong Liu, Canquan Mao","doi":"10.1016/j.ejphar.2024.177246","DOIUrl":"10.1016/j.ejphar.2024.177246","url":null,"abstract":"<p><p>FOXM1 is the \"Achilles' heel\" of cancers and hence the potential therapeutic target for anticancer drug discovery. In this work, we selected high affinity peptides against the protein of human DNA binding domain of FOXM1 (FOXM1-DBD) from the disulfide-constrained, phage displayed random cyclic heptapeptide library Ph.D.-C7C. We obtained a novel peptide, 9 R-CP29L, which was identified to be a potent anticancer peptide with IC₅₀ values of 9.0 and 11.1 μM at 24 h for HCCLM3 and MD-MBA-231 cells respectively. Molecular docking, CETSA, ITC and immunoblot assays demonstrated that 9 R-CP29L can potentially specifically bind to FOXM1-DBD with a K_d value of 1.25 μM and reduced the expression of FOXM1. In addition, Annexin V/PI flow cytometry, AO/EB staining, PI flow cytometry, clone formation and Transwell assays revealed that 9 R-CP29L also induced cell apoptosis and cell cycle arrest while inhibited the proliferation and migration of HCCLM3 cells. The findings were further supported by the results of qRT-PCR and immunoblot assays for the associated gene (CMYC, CDC25B, BAX, CASPASE3 and MMP2, etc) expression in HCCLM3 cells. Finally, in vivo experiment showed that 9 R-CP29 significantly reduced the tumor growth and downregulated the expression of FOXM1 in HCCLM3 xenograft nude mouse models. Taking together, our work provides a novel FOXM1 targeted peptide which has potential in both anticancer drug development and scientific researches.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177246"},"PeriodicalIF":4.2,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aspirin-triggered lipoxin A4 reduces neuropathic pain and anxiety-like behaviours in male diabetic rats: antinociceptive enhancement by cannabinoid receptor agonists.","authors":"Matheus Vinícius Ferreira, Carlos Henrique Alves Jesus, Jaderson Pedro Bonfim da Costa, Gabrielle Oliveira, Bruno Liebl, Waldiceu Verri Junior, Janaína Menezes Zanoveli, Joice Maria da Cunha","doi":"10.1016/j.ejphar.2025.177254","DOIUrl":"10.1016/j.ejphar.2025.177254","url":null,"abstract":"<p><p>Neuropathy is the most common complication of diabetes, leading to painful symptoms like hyperalgesia. Current treatments for diabetic painful neuropathy often prove inadequate, necessitating the exploration of new pharmacological approaches. Therefore, this study aimed to investigate the potential antinociceptive effect of aspirin-triggered lipoxin A4 (ATL), a specialized pro-resolving lipid mediator, when administered alone or in combination with cannabinoid agonists, to alleviate diabetic neuropathic pain. Mechanical hyperalgesia in the hindpaws of streptozotocin (STZ)-induced diabetic (DBT) rats was assessed using the electronic Von Frey test (VFT), before diabetes induction and for up to 32 days after STZ administration and intraperitoneal ATL (0.3, 1, 3, 10, or 30 ng/rat) treatment, alone or in combination with intrathecal CB1 or CB2 receptor agonists (ACEA or JWH-133, respectively; 10 or 30 μg/rat). The effect of ATL treatment on locomotor activity and anxious or depressive-like behaviors was also evaluated. In comparison to control normoglycemic rats, control DBT rats developed: 1) mechanical hyperalgesia; 2) increase in anxious and depressive-like behaviors. ATL treatment attenuated mechanical hyperalgesia in DBT rats both acutely (at 30 ng) and cumulatively (at doses of 1, 3, 10, or 30 ng), without compromising locomotor activity. The antinociceptive effect of ATL (at 1 or 3 ng) was augmented when combined with ACEA or JWH-133 treatments (only at a dose of 30 μg/rat). While ATL treatment alone reduced anxious-like behavior in DBT rats, it did not affect depressive-like behavior. These findings underscore the therapeutic potential of ATL, in diabetic complications, suggesting a possible interaction with the endocannabinoid system.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177254"},"PeriodicalIF":4.2,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transforming pharmacology education: Insights from the pharmacology education project in the era of digital learning.","authors":"John L Szarek, Clare Guilding, Simon Maxwell","doi":"10.1016/j.ejphar.2025.177258","DOIUrl":"10.1016/j.ejphar.2025.177258","url":null,"abstract":"<p><p>The IUPHAR Education Section's Pharmacology Education Project (PEP; www.pharmacologyeducation.org) provides an open-access, peer-reviewed platform to support pharmacology education globally. Launched in 2016, PEP offers a comprehensive range of freely accessible, peer-reviewed resources, including extensive topic summaries with links to videos, slide sets, and other media curated by pharmacologists and catering to diverse learners' needs. This paper provides an update on PEP's growth, providing analytics on user engagement and feedback. The platform averages 20,000 visits per month, with a peak of 50,000 during the COVID-19 pandemic. Engagement rates are approximately 40%, indicating robust interaction with the content. Feedback from 115 users spanning 31 countries praises the quality and quantity of PEP's resources and the ease of navigation through the website. Comparisons with traditional resources used in pharmacology education highlight PEP's advantages in accessibility and peer review. Examples of the use of PEP in education are provided, emphasizing active and self-directed learning methodologies. The discussion includes challenges in maintaining and expanding the platform, such as funding and content curation, and outlines strategies for sustainable development, including the role that artificial intelligence may play. PEP is a valuable resource in contemporary pharmacology education and plays a vital role in advancing the field globally.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177258"},"PeriodicalIF":4.2,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Concern: \"Fabrication, characterization, anti-inflammatory, and anti-diabetic activity of silver nanoparticles synthesized from Azadirachta indica kernel aqueous extract\" [Environ. Res., 208 (2022) 112684].","authors":"","doi":"10.1016/j.envres.2024.120629","DOIUrl":"10.1016/j.envres.2024.120629","url":null,"abstract":"","PeriodicalId":312,"journal":{"name":"Environmental Research","volume":"267 ","pages":"120629"},"PeriodicalIF":7.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Concern: \"Synthesis and characterization of TiO2 NPs by aqueous leaf extract of Coleus aromaticus and assess their antibacterial, larvicidal, and anticancer potential\" [Environ. Res., 200 (2021) 111335].","authors":"","doi":"10.1016/j.envres.2024.120610","DOIUrl":"10.1016/j.envres.2024.120610","url":null,"abstract":"","PeriodicalId":312,"journal":{"name":"Environmental Research","volume":"267 ","pages":"120610"},"PeriodicalIF":7.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Concern: \"The construction of novel CuO/SnO2@g-C3N4 photocatalyst for efficient degradation of ciprofloxacin, methylene blue and photoinhibition of bacteria through efficient production of reactive oxygen species\" [Environ. Res., 231 (2023) 116086].","authors":"","doi":"10.1016/j.envres.2024.120720","DOIUrl":"10.1016/j.envres.2024.120720","url":null,"abstract":"","PeriodicalId":312,"journal":{"name":"Environmental Research","volume":"267 ","pages":"120720"},"PeriodicalIF":7.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}