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Long-term thiethylperazine treatment in the Tg4-42 mouse model of Alzheimer's disease mouse: Therapeutic potential vs. adverse effects 长期巯基佩拉嗪治疗阿尔茨海默病小鼠Tg4-42模型:治疗潜力与不良反应
IF 2.5 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2026-01-01 Epub Date: 2025-11-09 DOI: 10.1016/j.pbb.2025.174127
Lisa Katharina Ruoff , Irina Wanda Helene Bänfer , Djavid Elias Liedtke , Sofie Elena China , Jens Wiltfang , Thomas A. Bayer , Sören Frederik Bock , Friederike Spandau , Caroline Bouter , Nicola Beindorff , Yvonne Bouter
{"title":"Long-term thiethylperazine treatment in the Tg4-42 mouse model of Alzheimer's disease mouse: Therapeutic potential vs. adverse effects","authors":"Lisa Katharina Ruoff ,&nbsp;Irina Wanda Helene Bänfer ,&nbsp;Djavid Elias Liedtke ,&nbsp;Sofie Elena China ,&nbsp;Jens Wiltfang ,&nbsp;Thomas A. Bayer ,&nbsp;Sören Frederik Bock ,&nbsp;Friederike Spandau ,&nbsp;Caroline Bouter ,&nbsp;Nicola Beindorff ,&nbsp;Yvonne Bouter","doi":"10.1016/j.pbb.2025.174127","DOIUrl":"10.1016/j.pbb.2025.174127","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and behavioral impairments. Thiethylperazine, a dopamine receptor antagonist with antiemetic and antidopaminergic properties, has been proposed as a potential therapeutic agent for AD. However, its impact on cognitive function in AD remains unclear.</div></div><div><h3>Aims</h3><div>This study investigated the long-term effects of thiethylperazine on memory, anxiety-like behavior, motor function, and AD pathology in Tg4-42 mice, a model characterized by Aβ4-42 overexpression and progressive neurodegeneration. Additionally, the impact of prolonged thiethylperazine treatment on behavioral outcomes and cerebral glucose metabolism in healthy adult C57BL/6J wild-type (WT) mice were examined.</div></div><div><h3>Methods</h3><div>Tg4-42 and WT mice were treated daily with 10 mg/kg thiethylperazine for 6 months, starting at 10 weeks of age. Memory, anxiety-related, and motor tests were performed at 7.5 months. Immunohistochemical analyses were conducted to quantify effects on Aβ pathology, neurogenesis, neuron number, and neuroinflammation. Additionally, <sup>18</sup>F-FDG-PET imaging was used to evaluate metabolic activity in WT mice following treatment.</div></div><div><h3>Results</h3><div>Thiethylperazine improved recognition memory in Tg4-42 mice in the Novel Object Recognition test and exhibited anxiolytic properties. However, it impaired spatial learning in the Morris Water Maze (MWM), reduced locomotion, and failed to mitigate motor impairments. No effects on neuron loss or neuroinflammation were observed. In WT mice, thiethylperazine altered learning processes in the MWM, as indicated by shifts in search strategies, induced hypometabolism and increased neurogenesis.</div></div><div><h3>Conclusion</h3><div>Although thiethylperazine offers mild cognitive benefits in Tg4-42, its adverse effects on learning strategies and locomotion raise questions about its potential as a therapeutic option for AD.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"258 ","pages":"Article 174127"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145496370","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}
引用次数: 0
1,4-Naphthoquinone improves depressive-like behaviors by modulating neuronal factors and neuroinflammatory mediators 1,4-萘醌通过调节神经因子和神经炎症介质改善抑郁样行为。
IF 2.5 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2026-01-01 Epub Date: 2025-11-20 DOI: 10.1016/j.pbb.2025.174133
Joo Hye Sim , Hye Jin Choi , Ohhyeon Kwon , Taeyeon Kim , Doheon Lee , Jeong June Choi
{"title":"1,4-Naphthoquinone improves depressive-like behaviors by modulating neuronal factors and neuroinflammatory mediators","authors":"Joo Hye Sim ,&nbsp;Hye Jin Choi ,&nbsp;Ohhyeon Kwon ,&nbsp;Taeyeon Kim ,&nbsp;Doheon Lee ,&nbsp;Jeong June Choi","doi":"10.1016/j.pbb.2025.174133","DOIUrl":"10.1016/j.pbb.2025.174133","url":null,"abstract":"<div><div>Depression is a chronic mental disorder characterized by alternations in emotions, thoughts, physical condition, and behavior. Using the natural product database Compound Combination-Oriented Natural Product Database with Unified Terminology (COCONUT) and the bioinformatics tool CODA (Context-Oriented Directed Associations), we screened and identified 1,4-naphthoquinone (1,4-NQ) as a promising candidate for depression treatment. Oral administration of 1,4-NQ attenuated the depressive-like behaviors in the open field test (OFT), elevated plus maze test (EPM) and forced swim test (FST) in a chronic restraint stress (CRS)-induced depressive-like mouse model. Real-time PCR analysis demonstrated that 1,4-NQ increased the mRNA levels of 5-HT1A and BDNF in the hippocampus of mouse brains. The expression level of glucocorticoid receptor (GR) in the hippocampus was increased by 1,4-NQ treatment in both CRS- and corticosterone-induced depression mouse models. We confirmed that 1,4-NQ has anti-neuroinflammatory efficacy by suppressing the levels of IL-6, TNF-α and IL-1β in LPS-stimulated BV2 microglial cell line. The western blot and real-time PCR analysis demonstrated that 1,4-NQ increased the level of GR in both the U-138 MG glial cell line and the SH-SY5Y neuronal cell line. In conclusion, 1,4-NQ is supposed to have anti-depressive efficacy by alleviating depressive-like behaviors through modulation of neuroinflammatory mediators and GR expression in the nervous system.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"258 ","pages":"Article 174133"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582441","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}
引用次数: 0
Adolescent stress differentially modulates the affective, psychomotor, and neural responses to a first amphetamine exposure in male Wistar rats 青春期应激对雄性Wistar大鼠初次接触安非他明的情感、精神运动和神经反应有差异调节。
IF 2.5 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2026-01-01 Epub Date: 2025-11-05 DOI: 10.1016/j.pbb.2025.174126
Andrey Sequeira-Cordero , Juan C. Brenes
{"title":"Adolescent stress differentially modulates the affective, psychomotor, and neural responses to a first amphetamine exposure in male Wistar rats","authors":"Andrey Sequeira-Cordero ,&nbsp;Juan C. Brenes","doi":"10.1016/j.pbb.2025.174126","DOIUrl":"10.1016/j.pbb.2025.174126","url":null,"abstract":"<div><div>The initial neurobehavioral adaptations following the first drug exposure may underlie the transition from recreational to compulsive use in vulnerable individuals. Compelling evidence indicates that early life adversity (ELA) is a significant risk factor for drug dependence. To better understand the relationship between ELA and initial drug experiences, we investigated whether chronic unpredictable stress (CUS) during adolescence modifies the affective (ultrasonic vocalizations, USVs), psychomotor (rearing and locomotion), and neural responses to a single dose of amphetamine in rats. CUS alone led to open-field hyperactivity and reduced flat USVs. CUS significantly blunted amphetamine-induced hyperactivity –suggesting a cross-tolerance effect– while it augmented amphetamine-induced appetitive 50-kHz calls, indicating a cross-sensitization effect. These results might suggest that CUS increases the rewarding and reduces the anxiogenic properties of initial amphetamine experience. At the neural level, amphetamine increased the expression of corticotropin-releasing factor (<em>Crf</em>)-related genes and the 2B subunit of the <em>N</em>-methyl-<span>d</span>-aspartate glutamate receptor (<em>Nr2b</em>) in a region-dependent manner. CUS upregulated the expression of brain-derived neurotrophic factor (<em>Bdnf</em>) in the medial prefrontal cortex (mPFC) and actin-related protein 2 (<em>Arp2</em>) in the nucleus accumbens (NAc). A cross-tolerance effect was observed for <em>Bdnf</em>, tropomyosin receptor kinase B (<em>TrkB</em>), and <em>Cofilin-1</em> in the mPFC. Conversely, the expression of Rho GTPase-activating protein 32 (<em>P250gap</em>), cAMP-response element binding protein (<em>Creb</em>), and DNA methyltransferase 3A (<em>Dnmt3a</em>) was cross-sensitized in the NAc. The coexistence of cross-sensitization and cross-tolerance neurobehavioral effects between CUS and amphetamine supports the idea that ELA can simultaneously blunt and heighten different brain substrates, collectively increasing the risk of drug dependence.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"258 ","pages":"Article 174126"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145471597","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}
引用次数: 0
Combination treatment with medium dose THC and CBD had no therapeutic effect in a transgenic mouse model for Alzheimer's disease but affected other domains including anxiety-related behaviours and object recognition memory 中剂量四氢大麻酚和CBD联合治疗在阿尔茨海默病转基因小鼠模型中没有治疗效果,但影响了其他领域,包括焦虑相关行为和物体识别记忆。
IF 2.5 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2025-12-01 Epub Date: 2025-09-19 DOI: 10.1016/j.pbb.2025.174101
Beate Aumer , Rossana Rosa Porto , Madilyn Coles , Nina Ulmer , Georgia Watt , Heike Kielstein , Tim Karl
{"title":"Combination treatment with medium dose THC and CBD had no therapeutic effect in a transgenic mouse model for Alzheimer's disease but affected other domains including anxiety-related behaviours and object recognition memory","authors":"Beate Aumer ,&nbsp;Rossana Rosa Porto ,&nbsp;Madilyn Coles ,&nbsp;Nina Ulmer ,&nbsp;Georgia Watt ,&nbsp;Heike Kielstein ,&nbsp;Tim Karl","doi":"10.1016/j.pbb.2025.174101","DOIUrl":"10.1016/j.pbb.2025.174101","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a neurodegenerative disease that effects memory and behaviour. The phytocannabinoid cannabidiol (CBD) has been found to reverse impairments of recognition as well as spatial memory deficits of AD transgenic mice but had only limited effects on disease-relevant brain pathologies. Recent evidence suggests that combining CBD with other cannabinoids including delta-9-tetrahydrocannabinol (THC) may lead to improved therapeutic outcomes. Thus, this study evaluated the chronic effects of combined treatment with 3 mg/kg THC and 20 mg/kg CBD on 14.5-month-old <em>APP</em><sub><em>Swe</em></sub><em>/PS1ΔE9</em> (<em>APP/PS1</em>) transgenic females and control littermates. Mice were treated with THCxCBD or vehicle (VEH) daily via intraperitoneal injections for 3 weeks before behavioural testing commenced. AD-relevant behavioural domains were analysed utilising Elevated Plus Maze (EPM), open field (OF), novel object recognition test (NORT), social interaction (SI), Y-maze (YM), and prepulse inhibition test (PPI). <em>APP/PS1</em> females showed an anxiety-like phenotype and object recognition deficits that remained unchanged by cannabinoid treatment. Interestingly, some effects of THCxCBD appeared genotype-dependent with cannabinoid treatment causing an anxiogenic EPM response in <em>APP/PS1</em> mice but having an anxiolytic-like effect in WT females. Moreover, THCxCBD administration disrupted the novel object preference of control females. Noteworthy, THCxCBD significantly decreased different fat depots and bodyweight of all mice across genotype. No other differences between genotypes or treatment groups were detected. In conclusion, the particular cannabinoid combination strategy utilised had no prominent therapeutic-like effect in 14.5-month-old <em>APP/PS1</em> females.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"257 ","pages":"Article 174101"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113968","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}
引用次数: 0
From morphine to buprenorphine - Modeling opioid use disorder and its treatment during pregnancy: Effects on maternal care and offspring neurodevelopment in a translational rodent model 从吗啡到丁丙诺啡-模拟阿片类药物使用障碍及其在妊娠期间的治疗:对母性护理和后代神经发育的影响在翻译啮齿动物模型。
IF 2.5 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2025-12-01 Epub Date: 2025-10-09 DOI: 10.1016/j.pbb.2025.174112
Lauren M. Richardson , Abigail M. Myers , Jecenia Duran , Deep K. Patel , Kit L. Tran , Ella R. Walsh , Shane A. Perrine , Scott E. Bowen , Susanne Brummelte
{"title":"From morphine to buprenorphine - Modeling opioid use disorder and its treatment during pregnancy: Effects on maternal care and offspring neurodevelopment in a translational rodent model","authors":"Lauren M. Richardson ,&nbsp;Abigail M. Myers ,&nbsp;Jecenia Duran ,&nbsp;Deep K. Patel ,&nbsp;Kit L. Tran ,&nbsp;Ella R. Walsh ,&nbsp;Shane A. Perrine ,&nbsp;Scott E. Bowen ,&nbsp;Susanne Brummelte","doi":"10.1016/j.pbb.2025.174112","DOIUrl":"10.1016/j.pbb.2025.174112","url":null,"abstract":"<div><div>Opioid use during pregnancy has increased drastically in the last two decades. Pregnant women who use opioids are often prescribed Medications for Opioid Use Disorder (MOUDs), including buprenorphine (BUP), to mitigate negative effects on the fetus. However, BUP exposure during pregnancy may still negatively impact maternal care behavior and offspring neurodevelopment. In the current study, we used a translational rodent model to investigate the effects of continued morphine or BUP use from preconception (7 days prior to mating) to the early postpartum period, as well as the transition from morphine to BUP during early pregnancy (gestational day (GD) 5), on both maternal care behaviors and acute offspring neurodevelopmental outcomes. Our results reveal that exposure to BUP beginning before pregnancy or on GD5 resulted in decreased nesting quality, maternal motivation, and pup-directed care behaviors as compared to controls. For the offspring, BUP-exposure resulted in increased pup mortality, more neonatal opioid withdrawal syndrome-like (NOWS) symptoms, altered norepinephrine levels in the brain, and decreased offspring weight, body length, and presence of milk bands compared to vehicle pups. Importantly, maternal care behavior was significantly correlated with offspring mortality, physical maturation, and NOWS-like scores, suggesting that at least some of the adverse effects were driven by impairments in maternal care. Morphine-exposed dams and pups showed overall fewer impairments compared to BUP-exposed dams and pups. This highlights that more research is needed to further understand the unique impact of BUP on the maternal brain and subsequent infant outcomes to mitigate potential adverse effects in pregnant women with MOUD prescriptions.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"257 ","pages":"Article 174112"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258850","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}
引用次数: 0
Zebrafish models: Charting promising platform and illuminating the depths of depression 斑马鱼模型:绘制有希望的平台,照亮抑郁的深度。
IF 2.5 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2025-12-01 Epub Date: 2025-09-16 DOI: 10.1016/j.pbb.2025.174097
Binqi Yang , Yu Han , Yuanjing Yang , Li Yuan , Xiaopeng Zhu
{"title":"Zebrafish models: Charting promising platform and illuminating the depths of depression","authors":"Binqi Yang ,&nbsp;Yu Han ,&nbsp;Yuanjing Yang ,&nbsp;Li Yuan ,&nbsp;Xiaopeng Zhu","doi":"10.1016/j.pbb.2025.174097","DOIUrl":"10.1016/j.pbb.2025.174097","url":null,"abstract":"<div><div>Depression, a prevalent mental disorder with significant global health implications, remains a complex and multifaceted challenge. Despite extensive research using traditional animal models and clinical trials, the underlying mechanisms of depression remain incompletely understood, hindering the development of effective treatments. Zebrafish (<em>Danio rerio</em>), with their remarkable genetic and neurobiological similarities to humans, have emerged as a powerful tool for investigating the complexities of depression. Zebrafish exhibit a rich and quantifiable behavioral repertoire, with assays such as the novel tank test, light–dark box, open field, shoaling, maze test, and tail immobilization used to assess depression-like phenotypes. Diverse modeling approaches (including genetic and pharmacological manipulations, chronic stress paradigms, and gut–brain axis studies) have been applied, enabling investigations into the physiological, genetic, pharmacological, and environmental drivers of depression. The integration of zebrafish into depression research offers unique opportunities to advance mechanistic insight and accelerate antidepressant discovery. This review summarizes recent progress, examines current challenges, and outlines future directions to maximize the translational potential of zebrafish depression models.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"257 ","pages":"Article 174097"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086850","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}
引用次数: 0
Creatine prevents ouabain-induced manic-like behavior by modulating GSK-3β via PI3K/AKT/mTOR pathway 肌酸通过PI3K/AKT/mTOR通路调节GSK-3β,阻止瓦苦因诱导的躁狂样行为。
IF 2.5 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2025-12-01 Epub Date: 2025-10-10 DOI: 10.1016/j.pbb.2025.174115
Adson Souza-Pereira , Jozyê Milena da Silva Guerra , Bruno Henrique Nieswald , Luan Machado Maidana , Amistron Benites Correa , Douglas Buchmann Godinho , Luiz Fernando Freire Royes , Leonardo Magno Rambo
{"title":"Creatine prevents ouabain-induced manic-like behavior by modulating GSK-3β via PI3K/AKT/mTOR pathway","authors":"Adson Souza-Pereira ,&nbsp;Jozyê Milena da Silva Guerra ,&nbsp;Bruno Henrique Nieswald ,&nbsp;Luan Machado Maidana ,&nbsp;Amistron Benites Correa ,&nbsp;Douglas Buchmann Godinho ,&nbsp;Luiz Fernando Freire Royes ,&nbsp;Leonardo Magno Rambo","doi":"10.1016/j.pbb.2025.174115","DOIUrl":"10.1016/j.pbb.2025.174115","url":null,"abstract":"<div><div>Bipolar disorder is a chronic psychiatric condition marked by alternating episodes of mania and depression. Current pharmacological treatments show limited efficacy and are often associated with incomplete remission. Creatine, a compound involved in energy buffering, mitochondrial function, and neuromodulation, has demonstrated neuroprotective and potential mood-stabilizing properties. However, the underlying mechanisms remain poorly understood. This study evaluated the effects of acute oral creatine administration (300 mg/kg) on behavioral and molecular changes in a validated rat model of mania induced by intracerebroventricular ouabain (10<sup>−3</sup> M), a Na<sup>+</sup>/K<sup>+</sup>-ATPase inhibitor. Behavioral alterations were assessed using the open field test, and hippocampal samples were analyzed for enzyme activity and key signaling proteins. Creatine significantly attenuated ouabain-induced hyperactivity and increased latency to symptom onset. At the molecular level, creatine preserved Na<sup>+</sup>/K<sup>+</sup>-ATPase activity and reduced phosphorylation of its α-subunit at a regulatory site. Additionally, creatine enhanced activation of the PI3K/AKT/mTOR/p70S6K pathway and prevented the ouabain-induced activation of GSK-3β, a kinase involved in mood regulation. Notably, rapamycin, an mTOR inhibitor, reversed the behavioral effects of creatine, suggesting a mechanistic role for this pathway. These findings demonstrate that acute creatine administration confers both behavioral and neurochemical protection in a mania model and supports its potential as an adjunctive therapeutic strategy for individuals with bipolar disorder.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"257 ","pages":"Article 174115"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280927","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}
引用次数: 0
Autophagy activation ameliorates cognitive deficits and alpha-synuclein pathology in an adeno-associated viral vector mediated rat model of Lewy body disorders 在腺相关病毒载体介导的路易体疾病大鼠模型中,自噬激活改善了认知缺陷和α -突触核蛋白病理。
IF 2.5 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2025-12-01 Epub Date: 2025-09-10 DOI: 10.1016/j.pbb.2025.174096
Elif Cinar , Gül Yalcin-Cakmakli , Hilal Akyel , Ayse Ulusoy , Banu Cahide Tel , Bülent Elibol
{"title":"Autophagy activation ameliorates cognitive deficits and alpha-synuclein pathology in an adeno-associated viral vector mediated rat model of Lewy body disorders","authors":"Elif Cinar ,&nbsp;Gül Yalcin-Cakmakli ,&nbsp;Hilal Akyel ,&nbsp;Ayse Ulusoy ,&nbsp;Banu Cahide Tel ,&nbsp;Bülent Elibol","doi":"10.1016/j.pbb.2025.174096","DOIUrl":"10.1016/j.pbb.2025.174096","url":null,"abstract":"<div><div>Lewy body disorders (LBD), including Parkinson's disease (PD), Parkinson's disease with dementia (PDD), and dementia with Lewy bodies (DLB), are characterized by the aggregation of alpha-synuclein (a-syn). Despite shared pathological features, these disorders have distinct clinical characteristics, in terms of both motor and cognitive symptoms.</div><div>We created a unique rat model of dual-site injection of adeno-associated viral vectors carrying human a-syn (AAV5-h-a-syn) simultaneously and bilaterally into the substantia nigra and dentate gyrus, to recapitulate both nigrostriatal and hippocampal-based a-syn pathology associated with PDD and DLB. Inspired by the distinct pathological features of the model, namely the CA2-dominated accumulation of phosphorylated a-syn, in the current study we aimed to evaluate comparatively the consequences of autophagic induction on a-syn pathology in these targeted areas. This was achieved by the chronic administration of rapamycin, for 8 weeks starting 10 weeks post-AAV injections. Behavioral assessments were conducted by evaluation of locomotor activity, anxiety-related behavior, object and spatial learning and memory. Histopathological examinations involved in-depth analysis of a-syn pathology, neuronal and synaptic integrity and autophagic markers.</div><div>Results demonstrated that rapamycin significantly ameliorated cognitive deficits and reduced phosphorylated a-syn accumulation, significantly in CA2 throughout all its sublayers and partially in CA3 sublayers. Despite no alteration in NeuN and TH levels, synaptophysin expressions were decreased in both the hippocampus and striatum in a-syn overexpressing animals, which were partially restored by rapamycin treatment. Intriguingly, autophagic activation, as indicated by the increased expression of beclin-1, LC3-I/II, p62, and Atg proteins, was predominantly observed in the hippocampus but not in the striatum, suggesting region-specific differential response to autophagic induction in terms of a-syn pathology.</div><div>This dual-site injection model provides a valuable tool for studying a-syn-related dementia and evaluating potential restorative therapies. Our findings underscore the importance of autophagy-targeting early interventions to alleviate cognitive deficits by reducing hippocampal a-syn burden in LBD.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"257 ","pages":"Article 174096"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054945","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}
引用次数: 0
Sex differences in acute tolerance to the objective and subjective effects of alcohol 酒精对客观和主观影响的急性耐受性的性别差异
IF 2.5 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2025-12-01 Epub Date: 2025-10-09 DOI: 10.1016/j.pbb.2025.174111
Annie K. Griffith, Mark T. Fillmore
{"title":"Sex differences in acute tolerance to the objective and subjective effects of alcohol","authors":"Annie K. Griffith,&nbsp;Mark T. Fillmore","doi":"10.1016/j.pbb.2025.174111","DOIUrl":"10.1016/j.pbb.2025.174111","url":null,"abstract":"<div><div>Alcohol is well known for impairing motor coordination and increasing subjective intoxication. Previous research has found that these effects are exacerbated in women, but such observations were limited to times when blood alcohol concentrations (BACs) were at or near peak. Interestingly, alcohol-induced impairment of motor coordination and subjective intoxication both demonstrate acute tolerance, meaning they recover faster than the decline of BAC as alcohol is eliminated. Consideration of acute tolerance to both measures in tandem is particularly important because if recovery from subjective intoxication outpaces recovery from objective motor impairment, a drinker may develop a false sense of freedom from the impairing effects of alcohol. Such a misjudgment can lead the drinker to engage in risky behavior as BAC declines. The present study examined whether sex differences were present in the acute tolerance to motor impairment and subjective intoxication. Twenty-five women and 25 men participated in a placebo-controlled study of their acute tolerance to motor impairment and subjective intoxication following a moderate dose of alcohol, 0.60 g/kg for women and 0.64 g/kg for men. Repeated assessments of motor coordination with a grooved pegboard and subjective intoxication with a visual analog scale were conducted seven times as BAC declined. While all participants demonstrated acute tolerance to both motor impairment and subjective intoxication, women exhibited significantly faster recovery from subjective intoxication than men. Consequently, women may be more likely than men to engage in risky behavior on the descending limb, such as alcohol-impaired driving.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"257 ","pages":"Article 174111"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258796","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}
引用次数: 0
Challenges in cross-test comparison of anxiety-related outcomes in rodents: A network meta-analysis 啮齿动物焦虑相关结果交叉测试比较的挑战:网络荟萃分析。
IF 2.5 3区 心理学
Pharmacology Biochemistry and Behavior Pub Date : 2025-12-01 Epub Date: 2025-10-13 DOI: 10.1016/j.pbb.2025.174116
Didem Derici Yıldırım , Özge Selin Çevik , Erdal Horata , Coşar Uzun
{"title":"Challenges in cross-test comparison of anxiety-related outcomes in rodents: A network meta-analysis","authors":"Didem Derici Yıldırım ,&nbsp;Özge Selin Çevik ,&nbsp;Erdal Horata ,&nbsp;Coşar Uzun","doi":"10.1016/j.pbb.2025.174116","DOIUrl":"10.1016/j.pbb.2025.174116","url":null,"abstract":"<div><div>Anxiety-like complex behavioral and psychological constructs are difficult to evaluate in rodents. Many studies have investigated which techniques are appropriate for measuring anxiety and related physiological parameters. Here, we used network meta-analysis to compare the current methods of assessing anxiety. We performed a comprehensive review and network meta-analysis by searching PubMed, EMBASE, the Cochrane Library, SCOPUS, and Web of Science for studies involving rodents with anxiety-related behaviors undergoing behavioral tests with certain keywords: The common parameters that emerged were total distance traveled, fecal boli count, and rearing behavior. In the 46 studies reviewed, the open-field test (OFT) and elevated plus maze (EPM) test appeared most often (in 45 and 43 studies, respectively), while the light–dark box (LDB) and elevated zero maze tests appeared less frequently (in two studies and one study, respectively Subsequently, the tests were ranked based on their likelihood of being the most effective measure for each outcome. For total distance traveled, the OFT showed a significant disadvantage over the EPM and LDB. For fecal boli, there was a significant difference between the LDB and OFT. There were no variations between tests in terms of rearing. Our findings reinforce the importance of considering each behavioral test's unique characteristics when selecting appropriate measures for anxiety-like behaviors. Researchers should exercise caution when interpreting single-measure outcomes and adopt a holistic approach that integrates multiple test results to achieve reliable and relevant conclusions. Network meta-analysis is a powerful tool for identifying the highlights, complexities, and inconsistencies of anxiety-related behaviors in rodents in preclinical anxiety models.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"257 ","pages":"Article 174116"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302625","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}
引用次数: 0
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