Behavioural Brain Research最新文献

{"title":"Adolescent CB1 receptor expression at the BLA and CA1 and acute AM251 effects on sociability and emotional memory are sex-specific, and not modulated by heterotypic stress exposure","authors":"Emmanuelle Person ,&nbsp;Hélène Plamondon","doi":"10.1016/j.bbr.2025.115704","DOIUrl":"10.1016/j.bbr.2025.115704","url":null,"abstract":"<div><div>Blockade of endocannabinoid CB1R has shown effects on adulthood sociability, memory and fear responses, under basal and stress conditions. In this study, we examined sex-specific effects of exposure to heterotypic stress in the prepubescent period, marked by maturation of brain systems, on endocannabinoid receptors expression, corticosterone secretion and effects of CB1 receptor blockade on social and cognitive responses. Sixty-four (N = 32 per sex) adolescent male and female rats were randomly assigned to a stress or no stress condition. Rats in the stress condition underwent a 10-day heterotypic stress paradigm alternating between restraint stress and forced swim exposure occurring between postnatal day (PND) 30 and PND39. On PND42 and PND44, rats pretreated with the cannabinoid 1 receptor (CB1) antagonist AM251 (1 mg/kg; i.p.) or a vehicle solution underwent behavioural testing in the social interaction and the Y-Maze passive avoidance tests. Our findings indicated acute CB1 antagonism to reduce sociability and fear memory, independently of sex or stress. Notably, baseline and stress-related corticosterone (CORT) detection indicated adolescent male to more rapidly habituate to stress exposure than female rats. Male rats also showed increased CB1 receptor expression at the basolateral amygdala and CA1 regions, although GR-ir remained unaltered. Together, our findings support observed sex- and region- specific differences in CB1 receptor expression during the adolescence period to be minimally influenced by prior heterotypic stress exposure.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"493 ","pages":"Article 115704"},"PeriodicalIF":2.6,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309495","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":"Effects of Fstl1 on neuroinflammation and microglia activation in lipopolysaccharide-induced acute depression-like mice","authors":"Qing Yang ,&nbsp;Wei Guo ,&nbsp;Ling Wang ,&nbsp;Yifei Zhang ,&nbsp;Yutao Tian ,&nbsp;Dong Ming ,&nbsp;Xi Xiao ,&nbsp;Jiajia Yang","doi":"10.1016/j.bbr.2025.115696","DOIUrl":"10.1016/j.bbr.2025.115696","url":null,"abstract":"<div><div>Depression is the most prevalent psychiatric illness, and its pathogenesis is associated with neuroinflammation. Follistatinlike protein 1 (FSTL1), a novel inflammatory protein, participates in the pathogenesis of diseases related to neuroinflammation. Therefore, we aimed to investigate the effect of FSTL1 in the pathogenesis of depression mediated using neuroinflammation-mediated models. Our results showed that lipopolysaccharide (LPS) administration could induce despair-like behavior and increase proinflammatory cytokine levels in both male and female mice. Then, a significant positive correlation between hippocampal <em>Fstl1</em> mRNA expression, microglial activation and despair-like behaviors was observed in male mice. Moreover, knockdown FSTL1 significantly reduced microglial activation and the expression of proinflammatory cytokines, while overexpression of <em>Fstl1</em> in hippocampus could exacerbate the activation of microglial under the LPS-induced condition in male mice. Mechanically, knockdown <em>Fstl1</em> inhibited LPS-induced activation of BV2 microglia and reduced the production of proinflammatory cytokines, thereby protecting the survival of HT22 neurons. In conclusion, our results implied that <em>Fstl1</em> may modulate despair-like behaviors through regulation of microglial activation and neuronal viability, which would lay the experimental and theoretical foundation for the neuroinflammatory mechanisms underlying depression.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"493 ","pages":"Article 115696"},"PeriodicalIF":2.6,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293191","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":"Blood-brain barrier permeability in CKD: Link with inflammation and cognitive and mood impairment in rats","authors":"Mickaël Bobot ,&nbsp;Amandine Bruyat ,&nbsp;Laurent Thomas ,&nbsp;Samantha Fernandez ,&nbsp;Alexandre Brodovitch ,&nbsp;José Boucraut ,&nbsp;Stéphane Burtey ,&nbsp;Vincent Nail ,&nbsp;Benjamin Guillet ,&nbsp;Guillaume Hache","doi":"10.1016/j.bbr.2025.115693","DOIUrl":"10.1016/j.bbr.2025.115693","url":null,"abstract":"<div><div>Chronic kidney disease (CKD) is associated with cognitive impairment. CKD is associated with increased permeability of the blood-brain barrier (BBB), resulting in increased cognitive impairment in animals and in humans. The aim of this study is to describe the inflammatory profile in blood and cerebro-spinal fluid (CSF) during a CKD model induced by adenine rich diet (ARD) in rats, in relation to BBB permeability and to explore the cognitive and mood impairment phenotypes. ARD rats displayed a 5-fold increase in BBB permeability, quantified with brain ^99 mTc-DTPA SPECT/CT isotopic imaging, without alteration of brain perfusion. CKD is associated with increased PDGFRß levels in CSF (445 ± 85.6 vs. 303 ± 104.9 pg/mL, <em>p = 0.03</em>), suggesting pericyte dysfunction, but not with CSF levels of inflammatory cytokines, despite increased systemic inflammation<strong>.</strong> Neurobehavioural evaluation highlighted that ARD rats had impairment of short-term spatial memory, social memory and depressive features but not anxiety. In conclusion, CKD induces systemic inflammation and BBB permeability associated with pericyte dysfunction and alteration of memory and depressive features in rats. BBB disruption seems to be a crucial mechanism involved in cognitive and mood impairment during CKD.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"493 ","pages":"Article 115693"},"PeriodicalIF":2.6,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263889","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":"Effects of adolescent social instability stress on social reward motivation and dopamine receptor expression in female and male rats","authors":"A.M. Leonetti ,&nbsp;A.C. Sheehan ,&nbsp;S.H. Murray. ,&nbsp;F.F. Burke ,&nbsp;B.C.J. Fletcher ,&nbsp;C.M. McCormick","doi":"10.1016/j.bbr.2025.115702","DOIUrl":"10.1016/j.bbr.2025.115702","url":null,"abstract":"<div><div>Social experiences in adolescence are known to modify ongoing brain and behavioural development. We previously reported that adolescent social instability stress (SS; daily 1 h isolation and pairing with a new cage partner from postnatal days 30–45) reduced social interaction in female and male rats. Here, we investigated whether adolescent SS reduced social motivation and altered dopamine receptor mRNA expression in brain regions involved in social reward in female and male Long-Evans rats. When tested in a social operant conditioning task in adolescence whereby nose-pokes at one gate provided access to a social stimulus and at the other did not, SS rats made more social nose-pokes during training than did CTL rats. SS rats did not differ from CTLs when increased effort was required on the progressive ratio test (PRT; progressively more nose-pokes required to open gate; measure of social motivation). In adulthood, however, SS and CTL rats did not differ during training, although SS female rats had reduced social motivation on the PRT. Further, social motivation was higher in female than in male rats. Irrespective of age at testing, SS rats had increased dopamine receptor subtype 2 (D2), but not dopamine receptor subtype 1, mRNA expression in the medial prefrontal cortex in both sexes and in the nucleus accumbens in female rats. Given the evidence that D2 signaling in such brain regions inhibits social behaviour, the present research suggests that the increase in D2 mRNA expression may underlie the deficits in social behaviour evident in SS rats.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"493 ","pages":"Article 115702"},"PeriodicalIF":2.6,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271574","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":"Evaluating alpha-synuclein proteinopathy and consequences for birdsong in zebra finch basal ganglia area X","authors":"Reed T. Bjork ,&nbsp;Famesh Z. Patel ,&nbsp;Madeleine S. Daly ,&nbsp;Julie E. Miller","doi":"10.1016/j.bbr.2025.115698","DOIUrl":"10.1016/j.bbr.2025.115698","url":null,"abstract":"<div><div>Lewy body pathology is a major hallmark of Parkinson’s Disease (PD) and other dementias. The process of Lewy body formation is largely driven by the aggregation of alpha-synuclein (αsyn), an abundant presynaptic chaperone protein that has been shown to propagate between neurons when misfolded. Preclinical animal models inducing αsyn aggregation in the brain have demonstrated a range of behavioral consequences, though studies connecting behavioral changes to specific features of pathology are lacking. Considering vocal impairment manifests early in individuals with PD and fails to resolve upon dopamine replacement, we examined the effect of αsyn proteinopathy on birdsong in adult male zebra finches to investigate these early mechanisms of PD-related vocal dysfunction. In this study, we describe a novel tool for measuring αsyn expression called the Border Expression Ratio (BER) based on the discrete physiological distribution of αsyn surrounding basal ganglia song center, Area X. Following overexpression of human αsyn in Area X using bilateral injections of adeno-associated virus, we show that BER can be used to measure regional αsyn proteinopathy, revealing a positive correlation between right hemisphere pathology and a reduction in the variation of harmonic syllable duration. Finally, we provide evidence of serine 129 phosphorylation—a biomarker for aggregated αsyn—in Area X and cortical song nucleus LMAN of αsyn-overexpressing finches, despite this residue not being conserved in zebra finch αsyn, indicating modification of the human transgene. Together, these findings provide a framework for future analyses investigating αsyn propagation over time and the effects on vocal behavior.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"493 ","pages":"Article 115698"},"PeriodicalIF":2.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282293","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":"The decision-making and outcome evaluation processes in the Stag Hunt Game: Evidence from neural electrophysiology","authors":"Xianjia Wang ,&nbsp;Wei Cui","doi":"10.1016/j.bbr.2025.115700","DOIUrl":"10.1016/j.bbr.2025.115700","url":null,"abstract":"<div><div>Cooperative behavior is widespread in human social interactions and helps to address social dilemma issues. The Stag Hunt Game is a classic model of social dilemmas, with no studies so far exploring the neural mechanisms behind individual cooperation in this context. To investigate the temporal dynamics of brain processing underlying individual decision-making behavior in social dilemmas, we recorded EEG data from 35 participants during a one-time, two-player Stag Hunt Game and analyzed the data using event-related potential (ERP) and event-related oscillation (ERO) techniques. The results showed that, in the decision-making phase of the game, choosing cooperation induced a smaller P2 amplitude, a larger P3 amplitude, and reduced theta band oscillations compared to choosing defection. In the outcome evaluation phase, loss feedback generated a more negative FRN amplitude, a smaller P300 amplitude, and reduced delta oscillations compared to gain feedback. This study provides preliminary electrophysiological evidence for understanding the dynamic brain processing and neural oscillatory characteristics of human cooperative behavior in the Stag Hunt Game.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"493 ","pages":"Article 115700"},"PeriodicalIF":2.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271573","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":"Methamphetamine-induced cognitive impairment: Evaluation of amyloid beta 40 and phosphorylated tau protein 217 in male users","authors":"Mushtaq T. Abood,&nbsp;Mustafa Taha Mohammed","doi":"10.1016/j.bbr.2025.115701","DOIUrl":"10.1016/j.bbr.2025.115701","url":null,"abstract":"<div><div>Methamphetamine (METH) addiction is one of the most illegal substances use disorder worldwide, resulting in social, medical, and psychological consequences. This stimulant of the central nervous system (CNS) has been linked with different physiological effects that lead to the onset of multiple health disorders. This study aimed to investigate cognitive impairment in individuals with METH addiction by analyzing levels of amyloid β 40 (Aβ40) and phosphorylated tau protein at threonine 217 (p-tau 217), as key biomarkers associated with neurodegeneration. Two groups of adult males were assigned in this study, one containing 75 males with no previous history of addiction, non-medical use of any type of drugs, and no history of neurodegenerative diseases. The other group contained 75 males confirmed with METH addiction (1–10 years), Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). Among the METH group, 44 % exhibited cognitive impairment based on these assessments. The levels of Amβ 40 and p-tau 217 protein increased significantly (<em>p</em> &lt; 0.001) in individuals with METH addiction compared to non-addicts’ group. Also, Amβ 40 and p-tau 217 protein were correlated positively (r = 0.443, <em>p</em> &lt; 0.001), as well as p-tau 217 and albumin (r = 0.346, <em>p</em> = 0.002). Moreover, Amβ 40 has shown significant impact as risk factor for cognitive impairment in individuals with METH addiction with OR of 1.074 (1.035–1.115 95 % CI). Thus, abusing METH may stimulate dysfunction in the memory, resulting in elevation of Amβ 40 and p-tau 217 protein which leads to hypomnesia, and ultimately may increase the risk of neurodegenerative pathology.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"493 ","pages":"Article 115701"},"PeriodicalIF":2.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263888","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":"Neuroprotective effects of quercetin on motor impairments and anxiety-like behaviors in a rat model of Parkinson’s disease","authors":"Maryam Yousefi ,&nbsp;Mohammad Ali Mirshekar ,&nbsp;Maryam Afsharfar ,&nbsp;Saeideh Arabmoazzen ,&nbsp;Elham Haghparast","doi":"10.1016/j.bbr.2025.115692","DOIUrl":"10.1016/j.bbr.2025.115692","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor impairments such as bradykinesia and rigidity, and non-motor deficits including anxiety. These phenomena are closely associated with underlying pathological processes including oxidative stress(OS) and mitochondrial dysfunction that arise from the degeneration of dopaminergic neurons in the substantia nigra. Recent studies have shown that flavonoids like quercetin have neuroprotective effects through antioxidant and anti-inflammatory properties. In this study, we aimed to evaluate the impact of quercetin on motor function, anxiety-like behaviors, and Interleukin-6 (IL-6) levels in hippocampal dentate gyrus tissue in a rat model of PD induced by 6-hydroxydopamine (6-OHDA) and examine the behavioral findings with the use of two doses (10 and 25 mg/kg) of quercetin. Forty male Wistar rats were divided into five groups: control, sham, Parkinson's, and two quercetin-treated PD groups (10 and 25 mg/kg), and 6-OHDA (8 μg/3 μl) was injected into the left medial forebrain bundle (MFB) in three of them to induce PD. The behavioral assessments evaluated motor function and anxiety-like behaviors, including apomorphine-induced rotation, rotarod, wire hanging, elevated plus maze, and open field tests. Our results indicate that quercetin treatment significantly reduced apomorphine-induced rotations, supporting the results of rotarod and wire hanging tests, improved motor coordination, with the 25 mg/kg dose showing greater efficacy. Quercetin also alleviated anxiety-like behaviors in a dose-dependent manner based on the results of the elevated plus maze and open field tests. In addition, the results showed a significant elevation of IL-6 in the hippocampus of PD rats compared to the control group, and quercetin treatment can reduce its levels, though the levels remained higher than in the sham and control groups. These findings suggest that quercetin ameliorates both motor and anxiety-like deficits in a 6-OHDA rat model of Parkinson’s disease, potentially through modulation of hippocampal neuro-inflammation, highlighting its promise as a multi-target therapeutic agent in PD.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"493 ","pages":"Article 115692"},"PeriodicalIF":2.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280697","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":"Litter reduction-induced obesity reduces masticatory performance and SERT expression in the mesencephalic trigeminal nucleus","authors":"Cynthya Myllena Martins Silva ,&nbsp;Isabeli Lins Pinheiro ,&nbsp;Renata Emmanuele Assunção Santos ,&nbsp;Fernanda Carolina Ribeiro Dias ,&nbsp;Nilian Cerqueira Azevêdo ,&nbsp;Lívia Maria de Lima Leoncio ,&nbsp;Sandra Lopes de Sousa ,&nbsp;Lígia Cristina Monteiro Galindo ,&nbsp;Raquel da Silva Aragão ,&nbsp;Kelli Nogueira Ferraz-Pereira","doi":"10.1016/j.bbr.2025.115694","DOIUrl":"10.1016/j.bbr.2025.115694","url":null,"abstract":"<div><h3>Introduction</h3><div>Studies associate obesity with poorer masticatory performance. Obese individuals have larger bite size, use fewer masticatory sequences, and chew faster, contributing to higher food intake. The mesencephalic trigeminal nucleus facilitates the transmission of sensory input from the oral cavity to coordinate orofacial movements during chewing and swallowing. The serotonin transporter (SERT) acts on serotonergic neurotransmission control and correlates with obesity parameters.</div></div><div><h3>Objective</h3><div>To evaluate the effect of obesity induced by litter size reduction on somatic and masticatory performance and serotonin transporter immunoreactivity in the mesencephalic trigeminal nucleus.</div></div><div><h3>Methods</h3><div>Wistar rats were distributed into a control group (CL; 9 pups per dam; n = 13) and a small litter group (SL; 3 pups per dam; n = 13), analyzing their body weight, brown and white adipose tissue weight, food intake during mastication, masticatory jaw movements, and serotonin transporter immunohistochemistry.</div></div><div><h3>Results</h3><div>The overfed group had greater body weight from postnatal day 14 onwards; greater food consumption through chewing, and fewer chewing sequences and cycles on postnatal day 22; and greater amounts of inguinal, epididymal, mesenteric, retroperitoneal, and brown fat on postnatal day 30. Overfed animals had longer chewing sequences and lower chewing rates; they also had lower expression of SERT-IR, larger diameter of neurons and lower neuronal density in the mesencephalic trigeminal nucleus.</div></div><div><h3>Conclusion</h3><div>Obesity induced by neonatal overnutrition leads to decreased SERT expression in the mesencephalic trigeminal nucleus, leading to less rhythmic chewing activity and greater food consumption during chewing. These findings show the importance of the relationship between obesity, chewing, and SERT expression.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"493 ","pages":"Article 115694"},"PeriodicalIF":2.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257295","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":"Environmental caffeine triggers oxidative stress and behavioral changes in Cyprinus carpio: Insights into neurotoxicity","authors":"Idalia Casas-Hinojosa ,&nbsp;Leobardo Manuel Gómez-Oliván ,&nbsp;Sandra García-Medina ,&nbsp;Luis Alberto Orozco-Hernández ,&nbsp;José Roberto Jerónimo-Juárez ,&nbsp;Diana Belén Onofre-Camarena ,&nbsp;Karina Elisa Rosales-Pérez ,&nbsp;Veronica Margarita Gutierrez-Noya ,&nbsp;José Manuel Orozco-Hernández ,&nbsp;Gustavo Axel Elizalde-Velázquez ,&nbsp;Marcela Galar-Martínez ,&nbsp;María Dolores Hernández-Navarro ,&nbsp;Octavio Dublán-García ,&nbsp;Hariz Islas-Flores","doi":"10.1016/j.bbr.2025.115695","DOIUrl":"10.1016/j.bbr.2025.115695","url":null,"abstract":"<div><div>Caffeine (CAF) is categorized as a central nervous system (CNS) stimulant, with effects varying based on factors like species, exposure duration, and dosage. The CNS regulates vital physiological processes and is notably sensitive to environmental pollutants, particularly oxidative stress due to its high lipid content. This study investigates the impact of CAF a known CNS stimulant, on juvenile <em>Cyprinus carpio</em> at various exposure levels (0, 500, 1250, 1750 and 2500 ng/L). Employing a holistic approach, we assessed the oxidative stress markers such as lipid peroxidation (LPX), hydroperoxides content (HPC), protein carbonyl content (PCC) and antioxidant responses superoxide dismutase (SOD) and catalase (CAT), alongside AChsterase (AChE) activity, behavioral patterns (Novel Tank Test, Dark &amp; Light Test), histological changes (H&amp;E staining), and gene expression (<em>adenosine receptor A1</em>, <em>adenosine receptor A2A, serca</em>, <em>ryr, i3pr</em>). Our findings indicate that increasing CAF concentrations correlate with heightened oxidative and antioxidant biomarker levels in the carp brain. Specifically, AChE activity diminished, reflecting neurotoxicity. Behaviorally, CAF displayed a biphasic influence: at lower concentrations (500 ng/L), it promoted locomotion and reduced anxiety, whereas at concentrations above 2500 ng/L, it suppressed locomotor activity and heightened anxiety-like behaviors. Notably, the highest concentration (2500 ng/L) resulted in significant histopathological changes, with a 45.9 % incidence of pathological alterations, predominantly vacuolization in the telencephalon and optic tectum. Gene expression analysis revealed an upregulation of <em>adenosine receptor A1</em> and <em>adenosine receptor A2A</em>, indicating variations in the CAF mechanism based on receptor interaction. Additionally, there was a positive regulation of genes involved in Ca^2 + signaling (<em>serca, ryr, i3pr</em>), crucial for cellular homeostasis and implicated in cellular neoplasia’s. The study conclusively demonstrates that while low CAF doses can have beneficial effects on mobility, higher doses lead to pronounced neurotoxicity, indicated by oxidative stress, enzymatic inhibition, anxiety-like behavior, cerebral histopathology, and gene expression dysregulation. These findings provide critical insights into the dose-dependent neurotoxic effects of environmental CAF exposure in aquatic vertebrates.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"493 ","pages":"Article 115695"},"PeriodicalIF":2.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240099","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}