Behavioural Brain Research最新文献

{"title":"Neonatal vocalization rate predicts future prosocial behavior in C57 BL/6J mice","authors":"Matthew S. Binder,&nbsp;Elise B. Cauley,&nbsp;Nicole I. Cofsky,&nbsp;Morgan O. Lemler","doi":"10.1016/j.bbr.2025.115560","DOIUrl":"10.1016/j.bbr.2025.115560","url":null,"abstract":"<div><div>Neonatal Ultrasonic vocalizations (USVs) are an innate form of mouse communicative behavior that are produced throughout the first two postnatal weeks. While neonatal USVs are commonly assessed, their relationship to future behaviors is largely unknown. In the present study, we addressed this by analyzing vocalizations in C57BL/6 pups throughout development. We then examined each animal’s anxiety, locomotion, depressive, prosocial, and aggressive behaviors in adolescence. To analyze the results, we used correlations and also divided the mice into a high and a low group according to quantitative measures of their vocalizations, using a median split design. For call rate, we found a large positive correlation between call rate and sociability, furthermore, high vocalizers were significantly more prosocial than low vocalizers. No other significant differences and significant correlations were found. When we controlled for the relative contribution of the weight, sex, litter size, and sex composition of the litter, as well as the duration, pitch and amplitude of the calls, we found that high vocalizers were still significantly more prosocial than low vocalizers, indicating that this relationship cannot be attributed to these other factors. When the data was split according to the pitch, duration, and amplitude of the vocalizations, no significant adolescent behavioral differences nor correlations were found. Similarly, the types of calls produced had minimal relevance to adolescent behaviors. Altogether, our study elucidated a long-term implication for USVs, finding that the number of USVs produced throughout early development is a significant predictor of an animal’s future prosocial behavior.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"486 ","pages":"Article 115560"},"PeriodicalIF":2.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of reward learning on inhibitory control in internet gaming disorder: Evidence from behavioral and ERP","authors":"Ziyu Mao ,&nbsp;Jing Huang ,&nbsp;Mengyue Zhang ,&nbsp;Meng Zhang ,&nbsp;Chenyue Zhao ,&nbsp;Zhengxing Liu ,&nbsp;Xiaoli Xing","doi":"10.1016/j.bbr.2025.115558","DOIUrl":"10.1016/j.bbr.2025.115558","url":null,"abstract":"<div><div>Reward dysregulation and deficits in inhibitory control significantly contribute to the development of internet gaming disorder (IGD). While prior research demonstrates that reward history influences individuals' inhibitory control, it remains unclear whether this effect extends to individuals with IGD. The primary aim of this study was to investigate whether individuals with IGD exhibit impairments in reward learning and whether prior reward learning influences their inhibitory control, using both behavioral and event-related potential (ERP) measures. This study first employed a probability selection task to examine potential impairments in reward learning among individuals with IGD. Next, a stop-signal task incorporating reward- and punishment-associated stimuli was used to further investigate the behavioral and electroencephalographic effects of prior reward learning on subsequent inhibitory control. Results revealed that during the reward-learning phase, the IGD group exhibited significantly longer response times than the control group in both the learning and transfer phases. Additionally, the feedback-related negativity amplitude in the IGD group was significantly lower than that in the control group. Conversely, the P3 wave amplitude induced by positive and negative feedback in the IGD group were significantly higher than in the control group. In the inhibitory control phase following reward learning, the Nogo-P3 wave amplitude in response to reward cues was significantly greater in the IGD group than in the control group. Moreover, within the IGD group, the Nogo-P3 wave amplitude evoked by reward cues was significantly larger than the amplitude evoked by loss cues. These findings suggest that reward learning is impaired in individuals with IGD and that stimuli with a prior reward history may compromise inhibitory control, potentially serving as a critical factor in addiction development in this population.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"486 ","pages":"Article 115558"},"PeriodicalIF":2.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738060","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":"Neuroanatomical basis of 5-HT1A receptor agonism in disruption of maternal behavior in rats","authors":"Lanlan Zhang ,&nbsp;Jinyue Pang ,&nbsp;Qiyan Feng,&nbsp;Jinmei Hao,&nbsp;Xin Gu,&nbsp;Xiayang Jiang,&nbsp;Shengmei Yang,&nbsp;Wanhong Wei,&nbsp;Ruiyong Wu","doi":"10.1016/j.bbr.2025.115554","DOIUrl":"10.1016/j.bbr.2025.115554","url":null,"abstract":"<div><div>The acute activation of serotonin 1 A (5-HT_1A) receptors appears to disrupt maternal behavior in rats; however, the underlying neuroanatomical mechanisms remain poorly understood. We employed two approaches to investigate the role of 5-HT_1A receptors in maternal behavior to address this knowledge gap. First, we used real-time polymerase chain reaction (PCR) to analyze 5-HT_1A receptor mRNA expression in female rats at different reproductive stages. We identified stage- and region-specific expression patterns, including temporary increases in the nucleus accumbens (NAc), ventral tegmental area (VTA), and dorsal raphe nucleus (DRN), as well as a temporary decrease in the medial prefrontal cortex (mPFC), amygdala, hippocampus, and ventromedial hypothalamic nucleus (VMH) during the perinatal, early, and middle postpartum periods. These findings suggest that coordinated 5-HT_1A activity across these brain regions is critical for normal maternal behavior. Second, we used c-Fos immunohistochemistry to elucidate the central mechanisms underlying the effects of the acute and repeated administration of 8-OH-DPAT (a 5-HT_1A receptor agonist, 1.0 mg/kg, sc.) on maternal behavior. Acute 8-OH-DPAT administration disrupted maternal behaviors, including pup retrieval, pup licking, nest building and hovering over pups, while simultaneously increased c-Fos expression in the mPFC, ventral bed nucleus of the stria terminalis (vBNST), NAc shell, lateral septum (LS), and medial amygdala (MeA). Disruptions in pup retrieval, pup licking and nest building persisted following five days of repeated 8-OH-DPAT treatment, whereas hovering over pups showed substantial recovery, returning to near-normal levels. Concurrently, c-Fos expression increased in the vBNST but decreased in the mPFC, MeA, and DRN. These results suggest that acute and repeated 8-OH-DPAT administration disrupts maternal behavior via distinct presynaptic and postsynaptic 5-HT_1A receptor mechanisms. This study highlights the complex regulatory role of 5-HT_1A receptor activity in maternal care and provides insights into the neuroanatomical and neurochemical mechanisms underlying maternal behavior.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"486 ","pages":"Article 115554"},"PeriodicalIF":2.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738061","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":"Do snakes alter our visual attention to food?","authors":"Songhe Li ,&nbsp;Justin R. Keene ,&nbsp;Breanna N. Harris ,&nbsp;James A. Carr","doi":"10.1016/j.bbr.2025.115550","DOIUrl":"10.1016/j.bbr.2025.115550","url":null,"abstract":"<div><div>The need to detect and avoid predators drives many aspects of foraging behavior. Snakes are historical predators of primates, but predator avoidance-foraging tradeoffs are rarely studied in humans. We examined whether humans have a detection bias for snake versus food images using eye-tracking technology in 76 undergraduate student participants (38 men, 38 women). We tested three questions: 1) Do humans exhibit a visual bias to snakes over food? 2) Does food palatability affect any visual bias to snakes? 3) Is the response to snakes specific for these predators or a generalized reaction to a visually evocative stimulus? We analyzed three metrics in balanced pairs of food and snake images and images normatively ranked for arousal (low, high) and emotional valence (negative and positive): saccade latency, gaze duration, and saccade bouts. There was a strong bias toward shorter saccade latency with the snake images relative to food images. Gaze duration and saccade bouts were significantly greater for snake images relative to food images. Food palatability had discrete effects on the visual bias to snake images. Finally, qualitatively similar effects on visual bias were observed in response to negative valence, high arousal non-snake images. While humans display a gaze bias to snakes over food, this bias may be related to the negative valence and high arousal linked to snake images rather than key visual features of snakes themselves.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"486 ","pages":"Article 115550"},"PeriodicalIF":2.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742098","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 working memory training on cognitive flexibility, dendritic spine density and long-term potentiation in female mice","authors":"Vasiliki Stavroulaki ,&nbsp;Lida-Evmorfia Vagiaki ,&nbsp;Orestis Nikolidakis ,&nbsp;Maria Zafeiri ,&nbsp;Maria E. Plataki ,&nbsp;Kyriaki Sidiropoulou","doi":"10.1016/j.bbr.2025.115555","DOIUrl":"10.1016/j.bbr.2025.115555","url":null,"abstract":"<div><div>Working memory (WM) is a cognitive ability that allows the short-term maintenance and manipulation of information for goal-directed behavior. The prefrontal cortex (PFC) and the hippocampus (HPC) are two brain regions implicated in WM task performance. Several studies indicate that training in WM (WMT) can enhance performance in various other cognitive tasks. However, our understanding of the neurobiological changes induced by WMT is very limited. Previous work from our lab showed that WMT enhances synaptic and structural plasticity in the PFC and HPC in male mice. In this study, we investigate the effect of WMT on cognitive flexibility and synaptic properties in PFC and HPC in adult female mice. To this end, female adult mice were split into 3 groups: a) mice that remained in their home cage (naïve), b) mice that performed the alternation task in the T-maze (non-adaptive) and c) mice that were trained in the delayed alternation task for 9 days (adaptive). The delayed alternation task was used for WMT. In one cohort, following the delayed alternation task, all mice were tested in the attention set-shifting (AST) task to measure cognitive flexibility, followed by harvesting of the brains for Golgi-Cox staining to study dendritic spine density. Our results showed that in female mice, there were no differences in AST performance among the three groups tested, however, the latency to make a choice was reduced in the adaptive group. With regards to dendritic spine density, no significant differences were identified in PFC while increased dendritic spine density was found in HPC of the adaptive group, compared to the naïve group. In a second cohort, acute brain slices were prepared after completion of the delayed alternation task to investigate the synaptic properties in the PFC and the HPC. Evoked field excitatory post-synaptic potential (fEPSP) recordings were performed in either PFC or HPC brain slices. Our results show that tetanic-induced long-term potentiation (LTP) in the PFC was not different among the three training groups. In the HPC, theta-burst induced LTP was significantly increased in the adaptive group also compared to the non-adaptive and naïve groups. These results reveal both similarities and differences of WMT on performance in the attention set-shifting task, dendritic spine density and LTP in females, compared to males.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"486 ","pages":"Article 115555"},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742099","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":"Sex-dependent behavioral alterations in BALB/c mouse bearing a non-CNS solid tumor","authors":"Isaias Gutierrez-Leal,&nbsp;Luisa M. Onofre-Alvarado,&nbsp;Diana Caballero-Hernández,&nbsp;Ana L. Cantú-Ruiz,&nbsp;Moises A. Franco-Molina,&nbsp;Ricardo Gomez-Flores,&nbsp;Patricia Tamez-Guerra,&nbsp;Cristina Rodríguez-Padilla","doi":"10.1016/j.bbr.2025.115556","DOIUrl":"10.1016/j.bbr.2025.115556","url":null,"abstract":"<div><h3>Background</h3><div>Peripheral tumors can alter the central nervous system activity leading to behavior alterations and cancer-related cognitive impairment (CRCI). Although commonly attributed to anti-cancer treatments, findings of CRCI in newly diagnosed cancer patients suggest that tumors alone may impair brain functions, including working memory and processing speed.</div></div><div><h3>Methods</h3><div>We assessed male and female mice behavior using a novel object recognition and a Y maze test along with the open field and burrowing tests. The tests were performed before and after tumor implantation (subcutaneous murine L5178Y-R lymphoma injection in the posterior hind limb), and through its progression to evaluate mobility, anxiety, motivation recognition, and spatial working memory.</div></div><div><h3>Results</h3><div>Male mice showed deficits in recognition memory, scoring a low novel object time exploration (42.26 % in males [<em>p</em> = 0.02] and 50.15 % [<em>p</em> = 0.53] in females). Spontaneous alternation was significantly impaired in both male (<em>p</em> = 0.01) and female (<em>p</em> = 0.03) mice. During tumor progression, only female mice showed decreased mobility in indicators such as average speed, mobility rate, and total distance in the open field test, as well as deficient burrowing activity, indicating a lack of motivation or sickness behavior. Our findings suggest that tumor burden is associated with behavioral alterations in a sex-dependent manner in a mouse model of lymphoma.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"486 ","pages":"Article 115556"},"PeriodicalIF":2.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727944","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":"MiR-29a-3p ameliorate behavioral deficiency in hypoxia-ischemia brain damage in neonatal mice by inhibiting BTG2","authors":"Qian Luo ,&nbsp;Xiaohui Xing ,&nbsp;Yan Song ,&nbsp;Bing Gu ,&nbsp;Quan Hu ,&nbsp;Weiyang Liu ,&nbsp;Yilei Xiao ,&nbsp;Zhen Wang","doi":"10.1016/j.bbr.2025.115552","DOIUrl":"10.1016/j.bbr.2025.115552","url":null,"abstract":"<div><div>It has been reported that miR-29a-3p played a part in series neurological disorders. However, it remains unclear whether miR-29a-3p participate in the pathological mechanism in hypoxia-ischemia (HI) brain injury. In this study, we detected the change of miR-29a-3p level in the ipsilateral cortex following HI brain injury and found that miR-29a-3p was significantly increased at 3 days in the ipsilateral cortex following HI insult in neonatal mice. Therefore, we further explored the role of miR-29a-3p in HI brain injury and its molecular mechanism. The results showed that miR-29a-3p mimics attenuated and miR-29a-3p antagomir aggravated brain infarction volume at 3 days following HI insult. We further found that overexpression of miR-29a-3p also suppressed apoptosis and neuroinflammation, reduced synaptic loss and prevent HI-induced microglial morphological changes 3 days following HI insult. Neurobehavioral tests revealed that overexpression of miR-29a-3p could improve both short-term and long-term behavioral defects after HI injury. Furthermore, we proved that miR-29a-3p targets B-cell translocation gene 2 (BTG2) and further inhibits the expression of Bax by luciferase reporter assay and qRT-PCR. Moreover, overexpression of miR-29a-3p, by applying liposomes through intranasal route, could also achieve the same therapeutic effect in HI injury. Our data showed that by inhibiting BTG2/Bax, increasing level of miR-29a-3p might serve as a strategy to prevent brain damage and behavioral deficiency in HI.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"486 ","pages":"Article 115552"},"PeriodicalIF":2.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727958","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 astrocytes in the dorsal hippocampus on anxiety-like and depressive-like behaviors in hemiparkinsonian rats","authors":"Yi-Wei Hu ,&nbsp;Jian Liu ,&nbsp;Zi-Han Qiu ,&nbsp;Xiao-Ying Li ,&nbsp;Juan Li ,&nbsp;Li Chen ,&nbsp;Tao Wang ,&nbsp;Xin-Feng Wang ,&nbsp;Zhong-Jie Feng ,&nbsp;Wan-Ting Bai ,&nbsp;Yuan Guo ,&nbsp;Li Zhang","doi":"10.1016/j.bbr.2025.115553","DOIUrl":"10.1016/j.bbr.2025.115553","url":null,"abstract":"<div><div>Anxiety and depression are the most common neuropsychiatric manifestations of Parkinson’s disease (PD) patients. Growing evidence have shown that the dorsal hippocampus (dHIPP) and astrocytes (AS) may be involved in regulating depression and anxiety, but the role and mechanism are still unclear, especially in PD-related depression and anxiety. Unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc) were used to establish the rat model of PD. Behavioral tests and measurement of monoamine levels in the depression and anxiety related brain regions were performed to investigate the effects of chemogenetic activation or inhibition of dHIPP AS on PD-related anxiety and depression. The present results showed that unilateral lesions of the SNc induced anxiety-like and depressive-like behaviors, decreased dopamine (DA) levels in some related brain regions, but did not change the density of glial fibrillary acidic protein-positive AS in the CA1, CA3 and dentate gyrus in rats. Chemogenetic inhibition of dHIPP AS significantly improved anxiety-like and depressive-like behaviors only in the lesioned rats, while chemogenetic activation of dHIPP AS had no effects on anxiety-like and depressive-like behaviors in sham-operated and the lesioned rats. Chemogenetic activation of dHIPP AS only decreased DA level in the ventral hippocampus (vHIPP) in sham-operated rats, while inhibition of dHIPP AS increased 5-hydroxytryptamine (5-HT) levels in the medial prefrontal cortex (mPFC) and vHIPP in sham-operated rats and also in the amygdala, mPFC, lateral habenula, dHIPP and vHIPP in the lesioned rats. These results indicate that chemogenetic inhibition of dHIPP AS improves the anxiety-like and depressive-like behaviors in the lesioned rats through the changes in monoamine in some brain regions.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"486 ","pages":"Article 115553"},"PeriodicalIF":2.6,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727939","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 mechanistic role of piracetam in the management of vascular dementia","authors":"Hayder M. Al-kuraishy ,&nbsp;Ali I. Al-Gareeb ,&nbsp;Duaa Eliwa ,&nbsp;Athanasios Alexiou ,&nbsp;Marios Papadakis ,&nbsp;Mubarak Alruwaili ,&nbsp;Gaber El-Saber Batiha","doi":"10.1016/j.bbr.2025.115551","DOIUrl":"10.1016/j.bbr.2025.115551","url":null,"abstract":"<div><div>Piracetam is a cyclic derivative of gamma aminobutyric acid, has a neuroprotective effect against neurodegenerative disease by inhibiting neuroinflammation. Piracetam augments the effect of acetylcholine on the muscarinic receptors thereby improving learning and memory. In addition, piracetam through modulation of ion channels increases the activity of different neurotransmitters involved in cognitive function. Excitingly, piracetam improves blood flow by increasing erythrocyte deformability and reducing adhesion of erythrocytes to the vascular endothelium by inhibiting fibrinogen; thus, it improves microcirculation and can be used in the management of vascular dementia (VaD). Also, piracetam improves cognitive function in VaD by reducing mitochondrial dysfunction and oxidative stress. Hence, piracetam has a neuroprotective effect against VaD. However, the exact neuroprotective mechanism of piracetam against the development and progression of VaD was not fully clarified. Consequently, this review attempts to discuss the potential effect of piracetam in VaD.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"486 ","pages":"Article 115551"},"PeriodicalIF":2.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725047","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 anxiety induced by conditioned fear on the expression of NMDA receptors and synaptic plasticity in the rat BLA","authors":"Yue-Heng Yan,&nbsp;Hong-Kun Wang,&nbsp;Zi-Hao Wang,&nbsp;Rui-Ze Wang,&nbsp;Ruo-Xuan Li,&nbsp;Li-Li Huang,&nbsp;Yan-Yan Wang","doi":"10.1016/j.bbr.2025.115547","DOIUrl":"10.1016/j.bbr.2025.115547","url":null,"abstract":"<div><div>NMDA receptors (NMDAR) are vital in CNS activities such as anxiety, memory, and cognition, and the neurobiological mechanisms behind anxiety disorders are exceedingly complicated. The \"glutamic acid theory\" posits that glutamate excitotoxicity is a key pathophysiological mechanism in anxiety disorders. However, the exact mechanism by which conditioned fear contributes to anxiety disorders remains unknown.Based on the conditioned fear-induced anxiety disorder model, this work aims to investigate changes in NMDAR and related proteins throughout the acquisition and expression of fear memory, as well as the impact on synaptic structural and functional plasticity. Injecting the NMDA receptor endogenous agonist D-Serine (50 μg/μL) and the noncompetitive antagonist MK-801 (1 μg/μL) into the lateral ventricle of the conditioned fear model rats, as well as conducting behavioral observations, show that NMDAR are closely involved in the development of conditioned fear-induced anxiety. Model rats showed significant changes in glutamate (Glu) and γ-aminobutyric acid (GABA) levels in the amygdala (BLA), as well as expression of NMDAR and downstream BDNF/TrkB signaling pathway components. At the same time, model rats exhibited synaptic and neuronal injury, aberrant long-term potentiation (LTP), and decreased expression of essential synaptic proteins SYP and PSD-95. In conclusion, our study demonstrates that NMDAR and synaptic plasticity play a critical role in the development of conditioned fear-induced anxiety, serving as an important reference for understanding the neurobiological underpinnings of anxiety disorders and providing insights into their treatment and new possible targets.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"486 ","pages":"Article 115547"},"PeriodicalIF":2.6,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708336","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}