Neuroscience Letters最新文献

{"title":"Exploring interhemispheric interaction in complex regional pain syndrome","authors":"C. Berryman ,&nbsp;G.L. Moseley ,&nbsp;T.R. Stanton ,&nbsp;B. Hordacre ,&nbsp;F. Di Pietro","doi":"10.1016/j.neulet.2024.138100","DOIUrl":"10.1016/j.neulet.2024.138100","url":null,"abstract":"<div><h3>Background</h3><div>Complex regional pain syndrome (CRPS) is characterised by sensorimotor disturbances in the painful limb, coupled with neuroimaging evidence of functional changes in the primary somatosensory cortex (S1). However, the interaction between S1 in both hemispheres is unknown; altered interhemispheric interaction may contribute to this disorder.</div></div><div><h3>Objective</h3><div>We conducted the first study of sensory interhemispheric interaction in CRPS, specifically S1. This is also the first study to compare S1 interhemispheric inhibition in both directions in healthy controls.</div></div><div><h3>Methods</h3><div>Somatosensory evoked potentials were read with electroencephalography following paired median nerve stimulation at interstimulus intervals of 20, 25 and 30 ms.</div></div><div><h3>Results</h3><div>There was an inhibitory effect of the non-dominant on the dominant hemisphere in controls (ß = −0.308, SE 0.089, [CI −0.535, −0.081], t (914.9) = -3.49, p = 0.003), driven by changes in the N20/P25 SEP (i.e. S1). Importantly, this pattern of interhemispheric interaction was not seen in CRPS; in the CRPS group there was no evidence of interhemispheric inhibition – in either direction.</div></div><div><h3>Conclusion</h3><div>Given the difference in interhemispheric inhibition between CRPS and control groups, the role of S1 interhemispheric inhibition in CRPS needs further investigation. This may shed light on the sensorimotor disturbances characteristic of this disorder.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"847 ","pages":"Article 138100"},"PeriodicalIF":2.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143143587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dopaminergic receptors involvement in the antidepressant-like effect of N-(3-((3-(trifluoromethyl)phenyl)selanyl)prop-2-yn-1-yl) benzamide in mice","authors":"Camila Simões Pires ,&nbsp;Marcia Juciele da Rocha ,&nbsp;Marcelo Heinemann Presa ,&nbsp;Narryman Pinto Zuge ,&nbsp;Evelyn Mianes Besckow ,&nbsp;Kauane Nayara Bahr Ledebuhr ,&nbsp;Natália Emanuele Biolosor Kuntz ,&nbsp;Benhur Godoi ,&nbsp;Cristiani Folharini Bortolatto ,&nbsp;César Augusto Brüning","doi":"10.1016/j.neulet.2025.138144","DOIUrl":"10.1016/j.neulet.2025.138144","url":null,"abstract":"<div><div>Major Depressive Disorder (MDD) directly impacts the lives of countless individuals worldwide, yet its causes remain incompletely understood. However, it is recognized that a deficiency in monoamines, including dopamine, may contribute to this disorder. <em>N</em>-(3-((3-(trifluoromethyl)phenyl)selenyl)prop-2-yn-1-yl) (CF₃SePB) is an organoselenium compound that presented antidepressant-like effect in mice related to modulation of serotonergic, but not noradrenergic system. To expand the knowledge about CF₃SePB mechanisms of action, this study aimed to evaluate the involvement of dopaminergic system in its antidepressant-like effect. Male Swiss mice were pre-treated with the haloperidol (0.05 mg/kg, i.p., a non-selective D₂ receptor antagonist), SCH 23390 (0.01 mg/kg, s.c., a D₁ receptor antagonist), and sulpiride (50 mg/kg, i.p., a D₂ receptor antagonist) 15 min before CF₃SePB (50 mg/kg, i.g.), and after 30 min of CF₃SePB administration the forced swimming test (FST) was performed. CF₃SePB presented an anti-immobility effect in the FST, demonstrated by increase in the latency to first episode of immobility and reduction of total immobility of mice, and the pre-treatment of mice with haloperidol, SCH 23390 and sulpiride prevented these effects, showing that the antidepressant-like effect of CF₃SePB is related to the modulation of the dopaminergic system, specifically the D₁ and D₂ receptors. In addition, in silico pharmacokinetic profiling of CF₃SePB predicted its low likelihood of inducing adverse effects and potential to cross the blood–brain barrier. These results expand the understanding of CF₃SePB mechanisms for its antidepressant-like effect, reinforcing the potential of this organonoselenium compound for developing new antidepressants.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"849 ","pages":"Article 138144"},"PeriodicalIF":2.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-overexpression of Atoh1, Pou4f3, and Gfi1 enhances the transdifferentiation of supporting cells into hair cells in the neonatal mouse utricle","authors":"Ming-Yu Hao ,&nbsp;Wei Su ,&nbsp;Jun-Yi Xu ,&nbsp;Zhong-Rui Chen ,&nbsp;Lu He ,&nbsp;Jing-Ying Guo ,&nbsp;Ke Liu ,&nbsp;Shu-Sheng Gong ,&nbsp;Guo-Peng Wang","doi":"10.1016/j.neulet.2025.138136","DOIUrl":"10.1016/j.neulet.2025.138136","url":null,"abstract":"<div><div>Hair cells (HCs) are essential for vestibular function, and irreversible damage to vestibular HCs in mammals is closely associated with vertigo. The stimulation of HC regeneration through exogenous gene delivery represents an ideal therapeutic approach for restoring vestibular function. Overexpression of Atoh1, Pou4f3, and Gfi1 (collectively referred to as APG) has demonstrated efficacy in promoting HC regeneration in the cochlea. However, the effects of APG on vestibular HC regeneration remain unclear. Here, we used adeno-associated virus-inner ear (AAVie) as a carrier to deliver APG to the utricles of neonatal mice and assessed the morphology and number of HCs and supporting cells (SCs) by immunofluorescence staining. GLAST^CreERT;Rosa26^tdTomato mouse line was used to trace SCs. The results showed that APG overexpression resulted in substantial SC transdifferentiation into HCs in the neonatal mouse utricle. Furthermore, APG overexpression maintained SC number by facilitating SC proliferation. Continuous Atoh1 overexpression caused stereocilia damage, which was alleviated by APG overexpression. This study highlights the potential of regulating multiple transcription factors to promote vestibular HC regeneration.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"849 ","pages":"Article 138136"},"PeriodicalIF":2.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Constraint-induced movement therapy combined with intermittent theta-burst stimulation improve synaptic plasticity by inhibiting neutrophils extracellular traps formation in ipsilateral primary motor cortex of stroke rats","authors":"Yan Hua ,&nbsp;Congqin Li ,&nbsp;Anjing Zhang ,&nbsp;Yuyuan Wang ,&nbsp;Ying Xing ,&nbsp;Zhanzhuang Tian ,&nbsp;Jian Hu ,&nbsp;Yulong Bai","doi":"10.1016/j.neulet.2025.138134","DOIUrl":"10.1016/j.neulet.2025.138134","url":null,"abstract":"<div><div>The effect of Constraint-induced movement therapy (CIMT) or Intermittent theta-burst stimulation (iTBS) alone is limited in improving motor function after a stroke. In this study, we explored the efficacy and possible mechanisms in combination of CIMT and iTBS through behavioral evaluation, RNA sequencing, Golgi staining, transmission electronic microscope (TEM), high-performance liquid chromatography (HPLC), western blotting (WB) and immunofluorescence. Firstly, we observed that combination therapy is safe and effective, and it can significantly reduce the number of immature dendritic spines and increase the number of functional dendritic spines, the amount of glutamate (Glu) and the expression of Glu1 receptor (Glu1R). Meanwhile, we have found a significant reduction in neutrophil extracellular traps (NETs) in the combination group, and correlation analysis showed that the number of NETs is negatively correlated with the number of functional dendritic spines and the expression of Glu1R. After Cl-amidine ((S) - N - (1-amino-5- (2-chloroacetamiprid) -1-oxopentan-2-yl) benzamide 2,2,2-trifluoroacetate salt, PAD4 inhibitors) application, combined therapy did not further improve motor function and the expression of Glu1R. Our results proved that CIMT combined with iTBS therapy is a better therapeutic intervention. It improved motor function and synaptic plasticity after a stroke by promoting the transformation of functional dendritic spines and the expression of Glu1R in the ipsilateral primary motor cortex. The reduction of NETs generation is one of the key targets within it.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"849 ","pages":"Article 138134"},"PeriodicalIF":2.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variable schedules of reinforcement do not reliably distinguish habit from goal-directed behavior","authors":"Evdokia Skalnik,&nbsp;Natalia Ivlieva","doi":"10.1016/j.neulet.2025.138132","DOIUrl":"10.1016/j.neulet.2025.138132","url":null,"abstract":"<div><div>Contemporary analyses of neurophysiological mechanisms of associative learning suggest that instrumental behavior can be controlled by separable action and habit processes. An increasingly broad range of human psychiatric and neurological disorders are now associated with maladaptive habit formation. The question of how the brain controls transitions into habit is thus relevant. Widely used training procedures that might differentially generate goal-directed actions or habits are variable schedules of reinforcement. Random interval schedules are known to generate habitual behavior compared with random ratio schedules Here, we report attempt to identify the behavioral characteristics of the bifurcation point of habitual and goal-directed behavior. We compared the time courses of learning in random ratio and random interval schedules with more common for neurophysiological researches parameters. Behavioral differences between schedules emerge early in learning. However, in outcome devaluation test we found that training in the random ratio schedule, but not in the random interval schedule, led to results interpreted as habitual behavior. This result is the opposite of what we expected based on previous research. We assume that the most commonly used variable schedules of reinforcement cannot serve as a reliable tool for analyzing neural mechanisms of habitual and goal-directed behavior.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"849 ","pages":"Article 138132"},"PeriodicalIF":2.5,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping the aging brain: Insights into microstructural changes from free water-corrected fractional anisotropy","authors":"Abigail E. Bower ,&nbsp;Jae Woo Chung ,&nbsp;Roxana G. Burciu","doi":"10.1016/j.neulet.2025.138120","DOIUrl":"10.1016/j.neulet.2025.138120","url":null,"abstract":"<div><div>Aging has a significant impact on brain structure, demonstrated by numerous MRI studies using diffusion tensor imaging (DTI). While these studies reveal changes in fractional anisotropy (FA) across different brain regions, they tend to focus on white matter tracts and cognitive regions, often overlooking gray matter and motor areas. Additionally, traditional DTI metrics can be affected by partial volume effects. To address these limitations and gain a better understanding of microstructural changes across the whole brain, we utilized free water-corrected fractional anisotropy (FAt) to examine aging-related microstructural changes in a group of 20 young adults (YA) and 24 older adults (OA). A voxel-wise analysis revealed that YA had higher FAt values predominantly in white matter tracts associated with both motor and non-motor functions. In contrast, OA showed higher levels of FAt primarily in gray matter regions, including both subcortical and cortical motor areas, and occipital and temporal cortices. Complementing these cross-sectional results, correlation analyses within the OA group showed that many of these changes are further exacerbated with increasing age, underscoring the progressive nature of these microstructural alterations. In summary, the distinct patterns of FAt changes in gray versus white matter with aging suggest different underlying mechanisms. While white matter FAt values decrease, likely due to axonal degeneration, the increase in gray matter FAt could reflect either compensatory processes or pathological changes. Including behavioral data in future studies will be crucial for understanding the functional implications of these microstructural gray matter changes and their effects on cognitive and motor functions.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"849 ","pages":"Article 138120"},"PeriodicalIF":2.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated exposure to antibiotics exhibits anxiety-like behaviors with a reduction in neurogenesis in the ventral hippocampus of dentate gyrus","authors":"Kohei Takahashi ,&nbsp;Kazuhiro Kurokawa ,&nbsp;Kazuya Miyagawa ,&nbsp;Atsumi Mochida-Saito ,&nbsp;Hiroshi Takeda ,&nbsp;Minoru Tsuji","doi":"10.1016/j.neulet.2025.138131","DOIUrl":"10.1016/j.neulet.2025.138131","url":null,"abstract":"<div><div>Disruption of gut microbiota balance is known to contribute to the development of anxiety; however, it remains unclear whether dysbiosis-induced anxiety involves the glycogen synthase kinase-3β (GSK-3β)/cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) pathway and neurogenesis in the ventral hippocampal dentate gyrus (DG). In this study, Male ddY mice were administered an antibacterial cocktail to induce dysbiosis. The dysbiosis model displayed anxiety-like behaviors in the hole-board and elevated plus-maze tests, decreased the phosphorylation levels of GSK-3β (Ser9) and CREB, decreased the expression level of BDNF in the ventral hippocampus, and reduced neurogenesis in the ventral hippocampal DG. This suggests that dysbiosis-induced anxiety-like behaviors are associated with reduced neurogenesis in the ventral hippocampal DG via the GSK-3β/CREB/BDNF pathway.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"849 ","pages":"Article 138131"},"PeriodicalIF":2.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Latent bladder hypersensitivity induced by neonatal cystitis in rats unmasked by segmental but not hetero-segmental inflammation","authors":"Timothy J. Ness,&nbsp;Cary DeWitte","doi":"10.1016/j.neulet.2024.138090","DOIUrl":"10.1016/j.neulet.2024.138090","url":null,"abstract":"<div><div>Rats which experienced neonatal bladder inflammation (NBI) have been demonstrated to exhibit latent bladder hypersensitivity with a nociceptive component that becomes unmasked by a second inflammatory insult as an adult. Manifested as augmented reflex and neuronal responses to urinary bladder distension (UBD), these NBI-induced changes are revealed by using inflammation of nearby structures as an adult pretreatment. The effect of inflammation in distant structures is not known. These studies examined visceromotor reflex responses and lumbosacral spinal dorsal horn neuronal responses to UBD in rats and compared effects of segmental (hindpaw) versus hetero-segmental (forepaw or face) inflammatory pretreatments in 192 female Sprague-Dawley rats raised from birth. On postnatal days 14–16 these rats underwent either NBI or control procedures. As adults, these rats received control injections or 0.1 ml Complete Freund’s Adjuvant (CFA) injections into one of four sites. Three days later they were studied in reflex or spinal single-cell neuronal experiments where responses were evoked by UBD. Visceromotor responses to UBD were more robust in rats which had injections in the hindpaw (either side) but were not significantly affected by forepaw or facial injections. Similar results were identified in L6/S1 neurons with more robust UBD-evoked responses observed in rats receiving hindpaw CFA injections but not forepaw injections. These results indicate that latent bladder hypersensitivity induced by NBI is made manifest by segmental, but not hetero-segmental inflammatory stimuli. This observation correlates with pain in patients with interstitial cystitis who often have flares in symptoms associated with inflammation of nearby structures.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"846 ","pages":"Article 138090"},"PeriodicalIF":2.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oligodendrocyte differentiation on murine decellularized brain tissue","authors":"Hinata Nishimura ,&nbsp;Aurelien Kerever ,&nbsp;Kana Kato ,&nbsp;Tatsuki Ono ,&nbsp;Shiomi Nakayama ,&nbsp;Takahiro Tanaka ,&nbsp;Ryusei Abe ,&nbsp;Eri Arikawa-Hirasawa","doi":"10.1016/j.neulet.2024.138079","DOIUrl":"10.1016/j.neulet.2024.138079","url":null,"abstract":"<div><div>Loss of oligodendrocytes causes severe neurological damage. Oligodendrogenesis is the production of new oligodendrocytes throughout life and includes several developmental stages starting from oligodendrocyte precursor cells (OPCs).</div><div>The GPR17-expressing cell population, an important intermediate stage in oligodendrocyte development, acts as a reservoir responding to brain injury and ischemia. GPR17 plays a complex role in oligodendrocyte maturation and response to injury; its activation promotes differentiation into more mature phenotypes. However, our understanding of GPR17-expressing oligodendrocytes <em>in vitro</em> remains limited.</div><div>No methods have been elucidated for studying these short-lived and changeable cell populations using culture systems.</div><div>The extracellular matrix (ECM) plays an important role in regulating the proliferation and differentiation of these cells; however, conventional two-dimensional culture systems cannot reproduce the complex structure and environmental conditions of the ECM <em>in vivo</em>.</div><div>Herein, a culture system with decellularized brain tissue that retains organized ECM scaffolds was introduced to better mimic the <em>in vivo</em> environment. This system enabled the study of interactions between OPCs, ECM, and other cell types. Neurospheres containing progenitor cells that differentiate into oligodendrocyte lineage cells, neurons, and astrocytes were transplanted into decellularized brain slices. The results showed that this method not only promoted stem cell differentiation but also significantly enhanced differentiation into oligodendrocytes when supplemented with oligo buffer.</div><div>This model system provides a better understanding of the interaction between OPCs and the ECM and a novel approach for studying the differentiation of GPR17-expressing cells, which may be useful for future therapeutic strategies for promoting remyelination and central nervous system repair.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"846 ","pages":"Article 138079"},"PeriodicalIF":2.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral administration of crocin reverses memory loss induced by ethanol and nicotine abstinence in adolescent male rats","authors":"Samaneh Kakhki ,&nbsp;Ali Abbaszade-Cheragheali ,&nbsp;Seyyed Pouria Tafti ,&nbsp;Atefeh Shirinzadeh Feizabadi ,&nbsp;S. Mohammad Ahmadi-Soleimani ,&nbsp;Farimah Beheshti","doi":"10.1016/j.neulet.2024.138077","DOIUrl":"10.1016/j.neulet.2024.138077","url":null,"abstract":"<div><h3>Purpose</h3><div>Regarding a wide variety of researches conducted with various therapeutic effect of crocin, the main constituent of saffron, the current study aims to assess the efficacy of crocin to improve learning and memory impairment caused by withdrawal following concurrent usage of ethanol (Eth) and nicotine (Nic) in adolescent male rats.</div></div><div><h3>Methods</h3><div>In order to test memory fucntion, Morris water maze and passive avoidance methods were applied in male Wistar rats undergone adolescent Nic-Eth withdrawal and the effect of crocin treatment was assessed at both behavioral and biochemical levels. The biochemical parameters included the inflammatory cytokines, indicators of oxidative stress and cholinergic metabolism within the hippocampla tissues. Animals were divided into 7 experimental groups as follows: 1) control (saline + saline), 2) nicotine + ethanol, 3–5) nicotine + ethanol + crocin (three doses), 6) nicotine + ethanol + bupropion + naloxone and 7) saline + crocin.</div></div><div><h3>Results</h3><div>Results indicated that crocin treatment effectively prevented the Nic-Eth withdrawal induced behavioral manifestations of memory impairment when assessed by Morris water maze and passive avoidance tests. In addition, the biochemical alterations (in inflammatory, oxidative and cholinergic parameters) induced by Nic-Eth withdrawal were also ameliorated in rats treated by crocin. Interestingly, the mentioned ameliorative effect of crocin was found to be dose-dependent in most experiments and almost equipotential to that of bupropion and naloxone co-administration, when administered at high doses.</div></div><div><h3>Conclusion</h3><div>We would like to suggest the crocin treatment as an alternative medication for the management of Nic − Eth withdrawal, however, further studies are required to assess the unknown side effects and high dose tolerability of the drug in human subjects.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"846 ","pages":"Article 138077"},"PeriodicalIF":2.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}