Psychopharmacology最新文献

{"title":"Corticotropin releasing hormone receptor 1 in the medial prefrontal cortex mediates aversion resistant alcohol intake.","authors":"Miranda E Arnold, Cecelia E Harber, Lauren A Beugelsdyk, Ellie B Decker Ramirez, Grace B Phillips, Jesse R Schank","doi":"10.1007/s00213-024-06707-5","DOIUrl":"10.1007/s00213-024-06707-5","url":null,"abstract":"<p><strong>Rationale: </strong>Alcohol consumption despite negative consequences is a core symptom of Alcohol Use Disorder. In animal models, this is studied by pairing aversive stimuli with alcohol access, and continuation of drinking under these conditions is known as aversion resistance. Previously, we found that female mice are more aversion resistant than males. Corticotropin releasing hormone (Crh) and the Crh receptor 1 (Crhr1) regulate stress-induced reinstatement, alcohol dependence, and binge-like drinking. However, the role of the Crh system in aversion resistance has not been assessed.</p><p><strong>Objectives: </strong>We aimed to identify sex differences in the Crh system during quinine-adulterated alcohol intake.</p><p><strong>Methods: </strong>We used two-bottle choice and adulterated the alcohol solution with quinine. Next, we measured Crh and Crhr1 levels in brain tissue using real-time polymerase chain reaction (RT-qPCR) and RNAscope in situ hybridization. We then infused a Crhr1 antagonist into the medial prefrontal cortex (mPFC) prior to quinine-alcohol intake.</p><p><strong>Results: </strong>After quinine-alcohol consumption, females exhibited increased mPFC Crhr1 mRNA levels as measured by RT-qPCR. This was confirmed with greater anatomical specificity using RNAscope, with females exhibiting an increased number of Crhr1 + cells in the dorsomedial PFC and the ventromedial PFC. mPFC Crhr1 antagonist treatment reduced quinine-alcohol consumption in females but did not impact consumption in males. Quinine-free alcohol intake was unaffected by Crhr1 antagonist treatment.</p><p><strong>Conclusions: </strong>Our findings suggest that Crhr1 in mPFC plays a role in aversion resistant alcohol intake in females. Future experiments will examine the sources of Crh innervation to the mPFC and their distinct roles in alcohol seeking.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2539-2550"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522801","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":"Fear generalization modulated by shock intensity and protein synthesis inhibitor.","authors":"Xinwen Dong, Yunyun Wang, Yudan Liu, Yonghui Li","doi":"10.1007/s00213-024-06662-1","DOIUrl":"10.1007/s00213-024-06662-1","url":null,"abstract":"<p><strong>Rationale: </strong>Maladaptive fear responses, including sensitized threat reactions and overgeneralization, contribute to anxiety disorders such as generalized anxiety disorder and post-traumatic stress disorder. Although stress intensity influences the generation and extent of these maladaptive fears, the underlying mechanisms remain unclear.</p><p><strong>Objectives: </strong>The present study examined whether varying footshock stress intensity and inhibition of protein synthesis have differential effect on fear sensitization and generalization in mice.</p><p><strong>Methods: </strong>Mice were subjected to a classic fear conditioning protocol involving five different levels of footshock intensities. Prior to fear acquisition, the protein synthesis inhibitor cycloheximide (CHX) was administered intraperitoneally. Fear sensitization to white noise and fear generalization to tones with frequencies differing from the conditioned tone were assessed at either 2 or 4 days after fear acquisition.</p><p><strong>Results: </strong>The results showed that, although varying shock intensities (except the lowest) led to a similar pattern of increased freezing during auditory cues in fear acquisition, the extent of both fear sensitization and generalization increased with the intensity of the footshock in the following days. As shock intensities increased, there was a proportional rise in sensitized fear to white noise and generalized freezing to tones with frequencies progressively closer to the conditioned stimulus. Mildest shocks did not induce discriminative conditioned fear memory, whereas the most intense shocks led to pronounced fear generalization. Administration of CHX before fear acquisition did not affect sensitized fear but reduced generalization of freezing to tones dissimilar from the conditioned stimulus in the group exposed to the most intense shock.</p><p><strong>Conclusions: </strong>Our results suggest that maladaptive fear responses elicited by varying stress intensities exhibit distinct characteristics. The effect of CHX to prevent overgeneralization without affecting discriminative fear memory points to potential therapeutic approaches for fear-related disorders, suggesting the possibility of mitigating overgeneralization while preserving necessary fear discrimination.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2627-2637"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894173","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":"A potential role of gut microbiota in stroke: mechanisms, therapeutic strategies and future prospective.","authors":"Manpreet Kaur, Khadga Raj Aran, Raju Paswan","doi":"10.1007/s00213-024-06708-4","DOIUrl":"10.1007/s00213-024-06708-4","url":null,"abstract":"<p><strong>Rationale: </strong>Neurological conditions like Stroke and Alzheimer's disease (AD) often include inflammatory responses in the nervous system. Stroke, linked to high disability and mortality rates, poses challenges related to organ-related complications. Recent focus on understanding the pathophysiology of ischemic stroke includes aspects like cellular excitotoxicity, oxidative stress, cell death mechanisms, and neuroinflammation.</p><p><strong>Objective: </strong>The objective of this paper is to summarize and explore the pathophysiology of ischemic stroke, elucidates the gut-brain axis mechanism, and discusses recent clinical trials, shedding light on novel treatments and future possibilities.</p><p><strong>Results: </strong>Changes in gut architecture and microbiota contribute to dementia by enhancing intestinal permeability, activating the immune system, elevating proinflammatory mediators, altering blood-brain barrier (BBB) permeability, and ultimately leading to neurodegenerative diseases (NDDs). The gut-brain axis's potential role in disease pathophysiology offers new avenues for cell-based regenerative medicine in treating neurological conditions.</p><p><strong>Conclusion: </strong>In conclusion, the gut microbiome significantly impacts stroke prognosis by highlighting the role of the gut-brain axis in ischemic stroke mechanisms. This insight suggests potential therapeutic strategies for improving outcomes.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2409-2430"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506712","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":"Association between angiotensin-converting enzyme gene insertion/deletion polymorphism and cognition impairment in patients with schizophrenia.","authors":"Li Mu, Dongmei Wang, Meihong Xiu, Xiang-Yang Zhang","doi":"10.1007/s00213-024-06657-y","DOIUrl":"10.1007/s00213-024-06657-y","url":null,"abstract":"<p><strong>Rationale: </strong>Several lines of evidence indicate that an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) gene may be involved in the pathogenesis of schizophrenia and cognitive impairment. However, the relationship between ACE I/D polymorphism and cognitive impairment in patients with schizophrenia remains unclear.</p><p><strong>Objectives: </strong>The aim of this study was to examine whether ACE gene I/D polymorphism contributed to cognitive impairment in Chinese patients with schizophrenia, and whether the association between clinical symptoms and cognitive impairment depended on different ACE genotypes.</p><p><strong>Methods: </strong>The ACE I/D polymorphism was genotyped in 928 schizophrenia patients and 325 healthy controls using a case-control design. The severity of psychopathological symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). Cognitive functioning was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).</p><p><strong>Results: </strong>There were significant differences in genotype and allele frequencies of the ACE I/D polymorphism between patients and healthy controls (both P < 0.01). After controlling for demographic characteristics, patients who are homozygous carriers of D and I performed worse on the RBANS attention index than heterozygous carriers (P = 0.009). In addition, attention index score was negatively correlated with PANSS negative symptom score in patients of all genotypes (all P < 0.05), and positively correlated with positive symptom score only in the I/I genotype (P = 0.005).</p><p><strong>Conclusions: </strong>These findings suggest that ACE I/D gene variants play a role in susceptibility to schizophrenia, specific cognitive impairment and the association between clinical symptoms and cognitive impairment in schizophrenia patients.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2551-2563"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889998","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":"Empagliflozin-activated AMPK elicits neuroprotective properties in reserpine-induced depression via regulating dynamics of hippocampal autophagy/inflammation and PKCζ-mediated neurogenesis.","authors":"Radwa N Muhammad, Mohammed A Albahairy, Mai A Abd El Fattah, Weam W Ibrahim","doi":"10.1007/s00213-024-06663-0","DOIUrl":"10.1007/s00213-024-06663-0","url":null,"abstract":"<p><strong>Rationale: </strong>Major depression has been an area of extensive research during the last decades, for it represents a leading cause of disability and suicide. The stark rise of depression rates influenced by life stressors, economic threats, pandemic era, and resistance to classical treatments, has made the disorder rather challenging. Adult hippocampal neurogenesis and plasticity are particularly sensitive to the dynamic interplay between autophagy and inflammation. In fact, the intricate balance between the two processes contributes to neuronal homeostasis and survival.</p><p><strong>Objectives: </strong>Having demonstrated promising potentials in AMPK activation, a major metabolic sensor and autophagy regulator, empagliflozin (Empa) was investigated for possible antidepressant properties in the reserpine rat model of depression.</p><p><strong>Results: </strong>While the reserpine protocol elicited behavioral, biochemical, and histopathological changes relevant to depression, Empa outstandingly hindered these pathological perturbations. Importantly, hippocampal autophagic response markedly declined with reserpine which disrupted the AMPK/mTOR/Beclin1/LC3B machinery and, conversely, neuro-inflammation prevailed under the influence of the NLRP3 inflammasome together with oxidative/nitrative stress. Consequently, AMPK-mediated neurotrophins secretion obviously deteriorated through PKCζ/NF-κB/BDNF/CREB signal restriction. Empa restored hippocampal monoamines and autophagy/inflammation balance, driven by AMPK activation. By promoting the atypical PKCζ phosphorylation (Thr403) which subsequently phosphorylates NF-κB at Ser311, AMPK successfully reinforced BDNF/CREB signal and hippocampal neuroplasticity. The latter finding was supported by hippocampal CA3 toluidine blue staining to reveal intact neurons.</p><p><strong>Conclusion: </strong>The current study highlights an interesting role for Empa as a regulator of autophagic and inflammatory responses in the pathology of depression. The study also pinpoints an unusual contribution for NF-κB in neurotrophins secretion via AMPK/PKCζ/NF-κB/BDNF/CREB signal transduction. Accordingly, Empa can have special benefits in diabetic patients with depressive symptoms.</p><p><strong>Limitations: </strong>The influence of p-NF-κB (Ser311) on NLRP3 inflammasome assembly and activation has not been investigated, which can represent an interesting point for further research.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2565-2584"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of the reinforcing, antinociceptive, and respiratory depressant effects of prototypical and G-protein biased mu-opioid receptor agonists in male and female Sprague-Dawley rats.","authors":"C Austin Zamarripa, Tanya Pareek, Loc M Pham, Bruce E Blough, Hayley M Schrock, Eric J Vallender, Kenneth J Sufka, Kevin B Freeman","doi":"10.1007/s00213-024-06690-x","DOIUrl":"10.1007/s00213-024-06690-x","url":null,"abstract":"<p><strong>Rationale: </strong>G-protein biased mu-opioid receptor (MOR) agonists have been reported to exhibit superior therapeutic windows compared to prototypical MOR agonists when relating antinociception to respiratory depression. However, there is relatively little research on the abuse potential of G-protein biased MOR agonists in relation to other behavioral endpoints.</p><p><strong>Objectives: </strong>The aim of the present study was to quantitatively compare the reinforcing, antinociceptive, and respiratory-depressant effects of the prototypical MOR agonists, fentanyl and oxycodone, to the G-protein biased MOR agonists, SR14968 and SR17018, in male and female rats.</p><p><strong>Methods: </strong>In the self-administration study, four separate groups of Sprague-Dawley (SD) rats self-administered intravenous (i.v.) fentanyl, oxycodone, SR14968, and SR17018 under a progressive-ratio schedule of reinforcement. Using a within-subjects design, separate cohorts of SD rats were tested with i.v. fentanyl, oxycodone, SR14968, and SR17018 using a hot-plate assay, assays of neuropathic and inflammatory antinociception, and whole-body plethysmography.</p><p><strong>Results: </strong>All MOR agonists functioned as reinforcers, but SR14968 and SR17018 were less efficacious relative to oxycodone and fentanyl. Moreover, all MOR agonists produced dose-dependent and fully efficacious antinociception across all nociception modalities. Oxycodone and fentanyl, but not SR14968 or SR17018, produced respiratory depression in a dose-dependent manner.</p><p><strong>Conclusion: </strong>The present results indicate that the G-protein biased MOR agonists tested herein produce MOR-typical antinociception, exhibit reduced but apparent abuse potential, and do not produce respiratory effects at doses that are above the antinociceptive range. Atypical MOR agonists within the SR series should be further studied as foundational molecules for the development of safter analgesics.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2453-2469"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352687","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":"BNST CRF receptor type 1 modulates mechanical hypersensitivity induced by adolescent alcohol exposure in adult female mice.","authors":"Natalia B Bertagna, Eleanor B Holmgren, Sheila A Engi, Linh Ha, Fabio C Cruz, Lucas Albrechet-Souza, Tiffany A Wills","doi":"10.1007/s00213-024-06693-8","DOIUrl":"10.1007/s00213-024-06693-8","url":null,"abstract":"<p><strong>Rationale: </strong>Alcohol exposure during adolescence has been linked to long-lasting behavioral consequences, contributing to the development of alcohol use disorder. Negative affect and chronic pain during alcohol withdrawal are critical factors influencing problematic alcohol use and relapse. Our previous research demonstrated that adolescent intermittent ethanol (AIE) vapor exposure elicits sex-specific negative affect-like behavior in adult mice following stress exposure. Additionally, AIE induces persistent mechanical hypersensitivity, which is accompanied by increased activation of corticotropin-releasing factor receptor type 1 (CRFR1) neurons in the dorsolateral bed nucleus of the stria terminalis (dlBNST).</p><p><strong>Objectives: </strong>This study extends previous work by investigating plasma corticosterone levels and CRFR1 protein expression in the dlBNST following restraint stress exposure in adult mice with an AIE history. We also aim to explore the role of dlBNST CRFR1 signaling in mediating negative affect-like behavior and mechanical hypersensitivity.</p><p><strong>Results: </strong>Female mice exhibited elevated plasma corticosterone levels compared to males following restraint stress. Moreover, females with AIE history showed higher expression of CRFR1 protein in the dlBNST compared to air controls. Antagonism of CRFR1 in the dlBNST blocked AIE-induced mechanical hypersensitivity in adult females but did not affect stress-induced negative affect-like behavior. In alcohol-naïve females, intra-dlBNST administration of a CRFR1 agonist induced mechanical hypersensitivity.</p><p><strong>Conclusions: </strong>These findings provide new insights into the neurobiological mechanisms underlying stress-induced negative affect and pain-related behavior, both influenced by a history of adolescent alcohol exposure. The results suggest that CRFR1 antagonists warrant further investigation for their potential in addressing alcohol-related chronic pain.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2513-2523"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352686","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":"Sex differences in morphine sensitivity of neuroligin-3 knockout mice.","authors":"Dieter D Brandner, Mohammed A Mashal, Nicola M Grissom, Patrick E Rothwell","doi":"10.1007/s00213-024-06660-3","DOIUrl":"10.1007/s00213-024-06660-3","url":null,"abstract":"<p><p>Sex has a strong influence on the prevalence and course of brain conditions, including autism spectrum disorders. The mechanistic basis for these sex differences remains poorly understood, due in part to historical bias in biomedical research favoring analysis of male subjects, and the exclusion of female subjects. For example, studies of male mice carrying autism-associated mutations in neuroligin-3 are over-represented in the literature, including our own prior work showing diminished responses to chronic morphine exposure in male neuroligin-3 knockout mice. We therefore studied how constitutive and conditional genetic knockout of neuroligin-3 affects morphine sensitivity of female mice, using locomotor activity as a proxy for differences in opioid sensitivity that may be related to the pathophysiology and treatment of autism spectrum disorders. In contrast to male mice, female neuroligin-3 knockout mice showed normal psychomotor sensitization after chronic morphine exposure. However, in the absence of neuroligin-3 expression, both female and male mice show a similar change in the topography of locomotor stimulation produced by morphine. Conditional genetic deletion of neuroligin-3 from dopamine neurons increased the locomotor response of female mice to high doses of morphine, contrasting with the decrease in psychomotor sensitization caused by the same manipulation in male mice. Together, our data reveal that knockout of neuroligin-3 has both common and distinct effects on morphine sensitivity in female and male mice. These results also support the notion that female sex can confer resilience against the impact of autism-associated gene variants.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2431-2440"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856294","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":"Aerobic exercise prevents and improves cognitive dysfunction caused by morphine withdrawal via regulating endogenous opioid peptides in the brain.","authors":"Shanghua Dai, Yigang Dong, Haifeng Shi, Jiawei Jin, Yixia Gan, Xinyi Li, Yongkang Wu, Fanglin Wang, Xinrui Zhu, Qingmiao Hu, Yi Dong, Yingmei Fu","doi":"10.1007/s00213-024-06698-3","DOIUrl":"10.1007/s00213-024-06698-3","url":null,"abstract":"<p><strong>Background: </strong>Morphine withdrawal leads to serious cognitive deficits in which dynorphins are directly involved. Recently, exercise has been shown to prevent and improve cognition dysfunction in a variety of ways. Meanwhile, exercise can regulate the endogenous opioid peptides including dynorphins. However, it remains unclear whether exercise influences cognitive dysfunction caused by morphine withdrawal via dynorphins. In the current study, we investigate the physiological mechanism of exercise prevention and improvement aganist cognition dysfunction caused by morphine withdrawal.</p><p><strong>Methods: </strong>Male, adult C57BL/6 mice were randomly divided into 5 groups : Saline control (WT), exercise (EXE), morphine withdrawl (MW), exercise + morphine withdrawl (EMW), morphine withdrawl + exercise (MWE). We established aerobic exercise prevention/improvement models, and conducted behavioral tests including Open field test (OFT), Temporal order memory test (TOM) and Y-maze. Through Western Blotting and immunofluorescence staining, we detected endogenous opioid peptides in hippocampus and mPFC.</p><p><strong>Results: </strong>Compared with MW group, EMW group and MWE group showed the same performance as WT group in TOM and Y-maze, with correct object recognition and memory ability. In Western Blotting and immunofluorescence staining experiments, it indicated that EMW group reduced the expression of PDYN and its fluorescence intensity in hippocampus; MWE group reduced the expression of OPRK1 and its fluorescence intensity in mPFC.</p><p><strong>Conclusion: </strong>Our data suggest that aerobic exercise can both prevent and improve cognitive dysfunction caused by acute morphine withdrawal via respectively down-regulating PDYN in the hippocampus and down-regulating OPRK1 in the mPFC. They may become new targets for drugs development in the future.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2525-2537"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473278","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":"Efficacy of Nigella sativa seed oil against psychophysical stress induced irritable bowel syndrome and anxiety-like symptoms in Wistar rats.","authors":"Madhu Sharma, Swati Rana, Shiwangi Aggarwal, Aitizaz Ul Ahsan, Muskan Budhwar, Sweety Mehra, Subhash Chandra Sahoo, Mani Chopra","doi":"10.1007/s00213-024-06713-7","DOIUrl":"10.1007/s00213-024-06713-7","url":null,"abstract":"<p><strong>Rationale: </strong>Stressors play a critical role in the progression of irritable bowel syndrome (IBS). Heterogenous stress causes alterations in our bowel movements which can further cause anxiety and depression-like symptoms, decreasing the ability of individuals worldwide to function in social, academic, and employment settings.</p><p><strong>Objectives: </strong>This study was aimed to investigate the effect of orally administered Nigella sativa (0.2 mL/kg b.wt.) seed oil (NSSO) on stress-induced IBS, anxiety, and depression-like symptoms in Wistar rats.</p><p><strong>Methods: </strong>In the present study, modelling IBS induced anxiety and depression-like symptoms in rodents have been employed to correlate the pathophysiological mechanisms behind this disorder. Moreover, evaluation of ameliorative potential of traditionally used NSSO in IBS was also carried out.</p><p><strong>Results: </strong>Present investigation indicated that acute stress of 1.5 h daily for 20 days induced hyper cortisol, gastrointestinal (GI) hypermotility, diarrhoea, altered levels of short chain fatty acids (SCFAs), and inflammation which are common symptoms of IBS. Furthermore, depression and anxiety-like symptoms were validated in test groups by various behavioral tests and decreased levels of 5-HT-Transporter mRNA gene expression, which are clear indicators of cognitive impairment.</p><p><strong>Conclusions: </strong>It is possible that these IBS-like symptoms may have contributed to the pathogenesis of cognitive deficits and depression. However, the anti-oxidative, anti-inflammatory, anti-spasmodic, and possibly the anti-anxiolytic properties of NSSO helped in the mitigation of altered gut-brain axis. Because the concurrent treatment of NSSO alleviated the symptoms of modified GI function and consequently, the anxious & depressive behavior of the animals. Overall, this research explored the protective efficacy of NSSO against stress-induced IBS and depression-like symptoms, shedding light on the potential of this natural compound as a therapeutic option in the field of gastroenterology and psychiatry.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2609-2626"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626879","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}