Psychopharmacology最新文献

{"title":"Adolescent female rats are resistant to the affective and cognitive impacts of Δ9-tetrahydrocannabinol exposure despite long-lasting molecular and neuronal disturbances in the hippocampal-hypothalamic network.","authors":"Marta De Felice, Hanna J Szkudlarek, Matthew J Jones, Taygun C Uzuneser, Mohammed H Sarikahya, Shawn N Whitehead, Walter J Rushlow, Steven R Laviolette","doi":"10.1007/s00213-025-06817-8","DOIUrl":"https://doi.org/10.1007/s00213-025-06817-8","url":null,"abstract":"","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-fat Fructose diet induces neuroinflammation and anxiety-like behaviors by modulating liver-brain axis communication.","authors":"Hongmei Du, Yuan Zhou, Jia Wang, Xianbing Bai, Borui Tao, Ming Chen","doi":"10.1007/s00213-025-06820-z","DOIUrl":"https://doi.org/10.1007/s00213-025-06820-z","url":null,"abstract":"<p><strong>Rationale: </strong>Patients with non-alcoholic fatty liver disease (NAFLD) may experience non-cognitive impairments such as anxiety and depression. However, the specific mechanism of the association between liver injury and neurological disorders is unclear.</p><p><strong>Objectives: </strong>In this study, we aimed to explore the relationship and underlying mechanism between high-fat fructose diet (HFFD)-induced liver injury and anxiety-like behavior in mice.</p><p><strong>Methods: </strong>A mouse model of NAFLD was established using an HFFD, and behavioral tests were performed to detect anxiety-like behaviors in mice; moreover, we used enzyme linked immunosorbent assay (ELISA) to detect glutamate levels in treated and normal diet (ND) mice, as well as to explore inflammation levels in mice using immunofluorescence and other methods.</p><p><strong>Results: </strong>Mice in the HFFD-treated group exhibited anxiety-like behaviors, as well as elevated serum lipid and glutamate levels, increased liver injury, and hepatic tissue fat accumulation. Additionally, HFFD-fed mice exhibited elevated levels of IL-6, IL-1β, and TNF-α in the liver, hippocampus, and cortex compared with the ND counterparts; HFFD-induced astrocyte and microglial activation was detected in the cortical and hippocampal regions. However, corilagin treatment alleviated these HFFD-associated pathological changes. Corilagin did not ameliorate anxiety behaviors in mice in the absence of liver injury.</p><p><strong>Conclusion: </strong>Our results indicated that the HFFD-induced NAFLD and mild hepatic fibrosis led to elevated levels of glutamate and aminotransferases, which infiltrated the brain, causing inflammation, and subsequently induced anxiety-like behaviors in mice. These pathological and behavioral manifestations were ameliorated through corilagin intervention. This study provides a possible underlying mechanism between HFFD and neurological disorders.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"D2 receptor activation modulates NMDA receptor antagonist-enhanced high-frequency oscillations in the olfactory bulb of freely moving rats.","authors":"Jacek Wróbel, Daniel Krzysztof Wójcik, Mark Jeremy Hunt","doi":"10.1007/s00213-025-06808-9","DOIUrl":"https://doi.org/10.1007/s00213-025-06808-9","url":null,"abstract":"<p><strong>Rationale: </strong>NMDA receptor antagonists, used to model psychotic-like states and treat depression, enhance the power of high-frequency oscillations (HFO) in many mammalian brain regions. In rodents, the olfactory bulb (OB) is a particularly important site for generating this rhythm. OB projection neurons express D1 and D2 receptors (D1R and D2R) which interact with NMDA receptors.</p><p><strong>Objectives: </strong>The aim of this study was to explore the effect of dopamine (DA) signalling in the OB on MK801-enhanced HFO.</p><p><strong>Methods: </strong>Local field potentials from the OB and locomotor activity were recorded in adult male freely moving rats. MK801 was injected systemically or infused locally to the OB. The effects of D1R and D2R agonists (SKF38393, quinpirole) and antagonists (SCH23390, eticlopride), administered systemically or locally to the OB, were examined on MK801-enhanced HFO. Effects of the antipsychotics risperidone and aripiprazole were also examined.</p><p><strong>Results: </strong>Local infusion of MK801 enhanced HFO power in the OB to levels similar to those observed after systemic injection. Neither systemic nor local blockade of D1R or D2R affected the MK801-enhanced HFO, despite reductions in hyperlocomotion. However, direct (systemic and local) D2R, but not D1R, stimulation caused a short-lasting reduction of MK801-enhanced HFO power and longer lasting reduction in frequency. Risperidone, but not aripiprazole, reduced MK801-enhanced HFO frequency.</p><p><strong>Conclusions: </strong>These results suggest that NMDA receptor antagonist-enhanced HFO in the OB is generated predominantly independently of DA influence, however exogenous stimulation of D2R can modulate this rhythm. A second, but not third generation antipsychotic reduced HFO frequency.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol mitigates activated astrocytes and microglia preventing Alzheimer's Disease (AD) progression and facilitates neuronal communication in Amyloid-β25-35 induced rat model for AD: A special emphasis on non-neuronal involvement in AD pathophysiology.","authors":"Kumar Surya, Anitha Rathinam, Meher Nisha Abubakkar, Kesavan Swaminathan Jayachandran, Mahesh Kandasamy, Muthuswamy Anusuyadevi","doi":"10.1007/s00213-025-06814-x","DOIUrl":"https://doi.org/10.1007/s00213-025-06814-x","url":null,"abstract":"<p><strong>Rationale: </strong>Amyloid deposits initiate neuroinflammation by activating astrocytes and microglia in the hippocampus, increasing neuronal vulnerability and loss. Astrocytes, while essential for cerebral function, can contribute to neuronal dysfunction by retracting neuronal synapses, that forms a consequence of neuroinflammation, leading to cognitive deficits in Alzheimer's disease (AD). Upon Amyloid-β (Aβ) deposition, astrocytes become reactive as part of a repair mechanism, however this process can impair neurogenesis resulting in AD progression.</p><p><strong>Objective: </strong>The current study hypothesizes that resveratrol (RSV) can address inflammation and promote neural regeneration, mitigating cognitive decline. Our previous research highlights RSV's homeostatic effect through SIRT1 normalization, which is crucial in preventing AD progression. However, its neurogenic potential in AD remains underexplored.</p><p><strong>Methods: </strong>In this study, Aβ25-35-induced AD rat model was used to study the anti-inflammatory, neurogenic and cellular homeostatic effect of RSV (30 mg/kg) for four weeks.</p><p><strong>Results: </strong>Results showed increased Doublecortin expressing cells, indicating favorable neurogenesis in hippocampus. Immunofluorescence of microglia and astrocytes in the hippocampus revealed that RSV counteracted their activation by reducing the formation of engulfing microglia and elongated astrocytes. Behavioral assessments using the Morris water maze and cued radial arm maze demonstrated significant improvements in spatial and learning memory. These cognitive improvements were supported by increased choline acetyltransferase and SIRT1 levels.</p><p><strong>Conclusion: </strong>These findings suggest that RSV effectively reduces neuroinflammation, promotes neurogenesis in the sub granular zone of the hippocampus, and improves learning and memory in both control and AD conditions via SIRT1. This study highlights RSV's potential as a suitable therapeutic agent for AD.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocannabinoid modulation of defensive state transitions to innate and learned threat.","authors":"Niharika Loomba, Anyu Cao, Senna Charles, Isaac Kandil, Michelle Kwon, Sachin Patel","doi":"10.1007/s00213-025-06812-z","DOIUrl":"https://doi.org/10.1007/s00213-025-06812-z","url":null,"abstract":"<p><p>A hallmark of many psychiatric disorders is maladaptive and heightened fear responses to non-threatening stimuli. Adaptive defensive responses to threats involve transitions between passive behaviors, such as freezing, and active escape strategies, such as darting or fleeing. The endocannabinoid (eCB) system, particularly 2-arachidonoylglycerol (2-AG), plays a crucial role in modulating fear and stress responses. However, the extent to which 2-AG influences defensive behavioral state transitions to fear responses remains unclear. To address this, we investigated the role of 2-AG in shaping defensive behaviors to learned and innate threats using pharmacological manipulations in both the serial compound stimulus (SCS) and the looming shadow paradigm. During SCS, inhibition of 2-AG synthesis enhanced freezing to early cues and promoted active responses during cues associated with heightened threat imminence. In the looming shadow paradigm, 2-AG depletion biased defensive behavior toward freezing and increased time spent in a safe zone, suggesting a shift toward passive responses. These findings demonstrate that 2-AG signaling critically regulates the balance and transitions between passive and active defensive strategies in both learned and innate fear contexts. Thus, 2-AG plays a key role in the scaling of defensive response transitions and the promotion of active defensive responses to threats.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telmisartan mitigates behavioral and cytokine level alterations but impairs spatial working memory in a phencyclidine-induced mouse model of schizophrenia.","authors":"Ana Carolina Dutra-Tavares, Julyana Gomes Maia, Thainá Pereira de Souza, Claudio Carneiro Filgueiras, Anderson Ribeiro-Carvalho, Alex Christian Manhães, Yael Abreu-Villaça","doi":"10.1007/s00213-025-06805-y","DOIUrl":"https://doi.org/10.1007/s00213-025-06805-y","url":null,"abstract":"<p><strong>Rationale: </strong>The central renin-angiotensin system (cRAS) is a neuromodulator system that has been associated with neuropsychiatric disorders. Mainly through angiotensin II type 1 (AT1) receptor activation, cRAS increases dopamine release in striatum, and modulates glutamate release and brain cytokine levels.</p><p><strong>Objectives: </strong>Considering that schizophrenia pathophysiology involves both neurotransmission and cytokine unbalance, we verified whether AT1 receptor blockade would have beneficial effects on a mouse model of schizophrenia.</p><p><strong>Methods: </strong>Phencyclidine, an NMDA receptor antagonist, was used to model schizophrenia in C57BL/6 male and female mice, while AT1 receptor antagonism was achieved by telmisartan administration. From postnatal day (PN) 60 to 70, mice received daily injections of telmisartan (0.25 or 1 mg/kg, i.p.) or saline, followed by phencyclidine (2.5 mg/kg, PN60-69; 10 mg/kg on PN70, s.c.) or saline. Mice were submitted to behavioral tests (PN63-70) and the frontal cerebral cortex and hippocampus were harvested.</p><p><strong>Results: </strong>Telmisartan lower dose reversed phencyclidine-evoked reduced levels of interleukin-6 and interleukin-10, as well as AT1 receptor downregulation in the frontal cortex. Its higher dose mitigated hyperactivity (schizophrenia-like positive symptomatology). Deleterious effects were also identified. Both telmisartan doses, when combined with phencyclidine, impaired spatial working memory, and caused prepulse inhibition deficits (an endophenotype of schizophrenia) at one prepulse intensity used, being most unfavorable at the lower dose.</p><p><strong>Conclusions: </strong>Despite evidence of beneficial effects, the telmisartan-mediated impairments observed in the phencyclidine model bring concerns as to the use of this AT1 receptor antagonist as a potential therapeutic agent in schizophrenia.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose-extending placebo effect in a rat model of buprenorphine maintenance treatment.","authors":"Kayla M Pitts, Emma M Pilz, Luana Colloca, Yavin Shaham, Jonathan J Chow","doi":"10.1007/s00213-025-06815-w","DOIUrl":"https://doi.org/10.1007/s00213-025-06815-w","url":null,"abstract":"<p><strong>Rationale and objective: </strong>Clinical studies have shown that exposure to placebos or combining placebos with a lower medication dose can mimic the effect of a higher effective medication dose. This \"dose-extending placebo effect\" has been demonstrated in treatment for pain and other medical conditions but not in addiction. Here, we tested if a \"dose-extending placebo effect\" occurs in a rat model of opioid (buprenorphine) maintenance.</p><p><strong>Methods: </strong>We trained 27 rats to self-administer remifentanil (5 µg/kg/infusion, 1-h per day). Next, we implanted some rats with buprenorphine minipumps (3 mg/kg/day, Exp. 1) or pretreated others with daily intravenous buprenorphine (0.3 mg/kg, Exp. 2), and introduced a discriminative cue (houselight + tone) during the self-administration sessions (the buprenorphine-maintenance cue). After discontinuing buprenorphine treatment, we retrained the rats for remifentanil self-administration without the cue. Next, we tested the effect of low and high buprenorphine doses (0.15 and 0.3 mg/kg), the buprenorphine-maintenance cue, and the combination of the low-dose with the cue on remifentanil self-administration.</p><p><strong>Results: </strong>Rats learned to self-administer remifentanil, and buprenorphine maintenance suppressed drug self-administration. The low buprenorphine dose modestly decreased self-administration, while the high dose caused a strong inhibition. Tests for the \"dose-extending placebo effect\" showed that discriminative buprenorphine cue alone had no effect, while the low dose plus the buprenorphine cue mimicked the inhibitory effect of the high dose.</p><p><strong>Conclusions: </strong>This proof-of-concept study suggests that a \"dose-extending placebo effect\" can be modeled in rats undergoing opioid maintenance. This approach could support dose-reduction strategies in humans undergoing opioid maintenance therapy.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xanthouhumol relieves stress-induced depressive-like behaviors through the Sirt1/NF-κB/NLRP3 pathway.","authors":"Gangqiang Lin, Yi Zhang, Jing Qin, Yong He, Li Fan, Qing Tan, Peng Xie","doi":"10.1007/s00213-025-06819-6","DOIUrl":"https://doi.org/10.1007/s00213-025-06819-6","url":null,"abstract":"<p><strong>Rationale: </strong>Depression is a complicated neuropsychiatric disorder with multifactorial etiology, involving alterations in behavior, neuroinflammatory processes, and oxidative homeostasis. Chronic stress disrupts synaptic plasticity and promotes neuroinflammation and redox imbalance, with pronounced effects in the medial prefrontal cortex (mPFC). Xanthohumol (XN), a prenylated flavonoid, has demonstrated neuroprotective properties; however, its therapeutic potential in the context of stress-induced depression has not been fully exploited.</p><p><strong>Objectives: </strong>This study aims to examine whether XN alleviates depressive-like behaviors in a chronic unpredictable mild stress (CUMS) mouse model, as well as to delve into the underlying mechanisms involving neuroinflammation, oxidative stress, synaptic function, and the Sirt1/NF-κB/NLRP3 signaling pathway.</p><p><strong>Methods: </strong>Male C57BL/6J mice were subjected to a 3-week CUMS protocol and administered XN at a dose of 20 mg/kg via intragastric gavage. Behavioral evaluations included the sucrose preference test, tail suspension test, and forced swim test to assess anhedonia and behavioral despair. mPFC tissues were collected for analysis of neuroinflammatory cytokines, Nissl staining, immunofluorescence, oxidative stress biomarkers, and synaptic protein expression. In addition, protein levels of Sirt1, phosphorylated NF-κB (phospho-NF-κB), total NF-κB, and NLRP3 in the mPFC were quantified via western blotting analysis.</p><p><strong>Results: </strong>XN treatment significantly ameliorated depressive-like behaviors and enhanced synaptic protein expression within the mPFC. XN markedly diminished the pro-inflammatory cytokines expression and attenuated oxidative stress via the activation of the Nrf2/HO-1 signaling pathway, thereby boosting the brain's antioxidant capacity. Additionally, XN upregulated the expression of Sirt1 and suppressed the NF-κB/NLRP3 inflammasome pathway activation.</p><p><strong>Conclusions: </strong>XN exerts antidepressant-like impact through the Sirt1/NF-κB/NLRP3 and Nrf2/HO-1 pathways, highlighting XN as a potentially effective therapeutic alternative for stress-induced depression.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preconceptual paternal ethanol drinking induces sexually dimorphic behavioural changes across 2 generations.","authors":"Sahir Hussain, Darren Day, Bart A Ellenbroek","doi":"10.1007/s00213-025-06807-w","DOIUrl":"https://doi.org/10.1007/s00213-025-06807-w","url":null,"abstract":"<p><p>This study aimed to assess both the inter and transgenerational impacts of preconceptual paternal ethanol Exposure (PPEE) using a rat model. Sprague Dawley male rats (F0) underwent chronic voluntary ethanol intake and at the end of the drinking paradigm were kept for one spermatogenesis cycle before being mated with ethanol naïve females. The litters and matched controls were behaviourally assessed, and a cohort of F1 males mated to observe a F2 generation. PPEE caused behavioural changes in both the F1 and F2 generations, including altering litter sizes and delaying development. The F1 also show a reduction in sensitivity to the motor impairing effects of ethanol compared to controls. Sexually dimorphic effects were seen with female offspring having a reduced preference to ethanol in both the F1 and F2, while tolerance to ethanol induced motor coordination was seen in the F2 females but not F2 males. Likewise, F1 males presented reductions in locomotor activity but these effects did not persist in the F2. The findings show PPEE induces transgenerational changes in development, drinking behaviour and ethanol sensitivity in a sexually dimorphic manner. These changes may be protective to the female offspring of PPEE to modify their ethanol intake. The alterations demonstrate potential far-reaching consequences for the metabolism of xenotoxic substances extending beyond ethanol and provides evidence to support developmental and behavioural changes across generations due to paternal alcohol consumption.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early maternal separation potentiates the impact of later social isolation in inducing depressive-like behavior via oxidative stress in adult rats.","authors":"Yating Chen, Jingjing Du, Mengzhu Lei, Na Ji, Wei Zhang, Chuanyu Li, Bo Zhang","doi":"10.1007/s00213-025-06811-0","DOIUrl":"https://doi.org/10.1007/s00213-025-06811-0","url":null,"abstract":"<p><strong>Rationale: </strong>Individuals who have experienced early life stress (ELS) are more vulnerable to later life stress induced depression, which might attribute to ELS potentiated impact of later life stress. The presumption and neurobiological mechanisms involved require further validation and elucidation.</p><p><strong>Objectives: </strong>To investigate impact of pre-weaning maternal separation (MS) on post-weaning social isolation (SI) in inducing depressive-like behavior, and involvement of central oxidative stress, glutamatergic and brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling in the process.</p><p><strong>Methods: </strong>Male offspring were exposed to MS, SI or maternal separation and social isolation (MSSI) stress, respectively. Subjects were treated with saline, antioxidant diallyl disulfide (DADS) (30 mg/kg, i.g.) or antidepressant fluoxetine (10 mg/kg, i.p.), for two weeks before behavioral tests in adolescents or adults. Depressive-like behavior was assessed with sucrose preference, forced swim and tail suspension tests. Concentrations of 4-hydroxynonenal (4-HNE), glutathione and superoxide dismutase in hippocampus and serum, and hippocampal protein expressions of glutamate transporter 1 (GLT-1), BDNF and TrkB were assessed by western blotting analysis.</p><p><strong>Results: </strong>MSSI, rather than MS or SI, induced significant depressive-like behavior, in adults but not adolescents. Consistently, only MSSI significantly elevated 4-HNE, whereas inhibited GLT-1, BDNF and TrkB in adult hippocampus. MSSI induced behavioral and biochemical abnormalities in adults were reversed by DADS or fluoxetine treatment.</p><p><strong>Conclusions: </strong>Early MS age-dependently potentiates later SI impact in inducing depressive-like behavior in male rats, through elevating oxidative stress and interrupting glutamatergic and BDNF/TrkB signaling in the brain. Results further suggest antioxidant treatment as a promising anti-depressant avenue.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}