Neuropharmacology最新文献

{"title":"Esketamine ameliorates prenatal stress-induced postpartum depression and sex-related behavioral differences in adolescent progeny","authors":"Yazhou Wen ,&nbsp;Jin Zhou ,&nbsp;Huiling Yu ,&nbsp;Zixin Wu,&nbsp;Rui Peng,&nbsp;Chenyang Xu,&nbsp;Xueduo Shi,&nbsp;Ming Jiang,&nbsp;Hongmei Yuan,&nbsp;Shanwu Feng","doi":"10.1016/j.neuropharm.2025.110354","DOIUrl":"10.1016/j.neuropharm.2025.110354","url":null,"abstract":"<div><h3>Background</h3><div>Prenatal stress leads to postpartum depression and is associated with developmental issues in offspring. Esketamine quickly and effectively prevents or treats postpartum depression. However, the long-term effects of esketamine on progeny development are unknown.</div></div><div><h3>Methods</h3><div>CRS during pregnancy was used to establish the postpartum depression animal model. After confirming pregnancy, all mice were randomly divided into three groups: pregnant control group, pregnant restraint group, and pregnant restraint + esketamine group. Mice in the restraint + esketamine group received esketamine intraperitoneal injection on postpartum days 1–5. Behavioral tests were performed on maternal mice five days after delivery. Another cohort of mice was used to test the effects of esketamine on the behavior of offspring mice. The levels of ACTH and CORT were measured in offspring mice in response to acute restraint stress by ELISA.</div></div><div><h3>Results</h3><div>We found that prenatal CRS induced postpartum depression-like behaviors in maternal mice and sex-related differential behaviors in adolescent offspring. Female offspring exhibited depression-like behaviors, and male offspring showed memory deficits. Esketamine improved postpartum depression-like behaviors in maternal mice and behavioral changes in teenage offspring. Prenatal CRS led to hyperresponsiveness of ACTH and CORT to acute restraint stress in adolescent offspring. Compared with the offspring in the control group, the restraint group increased secretion of ACTH and CORT during acute restraint stress.</div></div><div><h3>Conclusion</h3><div>Prenatal CRS led to postpartum depression-like behaviors in maternal mice and sex-related differential behaviors in adolescent offspring. Esketamine effectively improves postpartum depression-like behaviors in maternal mice and behavioral changes in adolescent offspring.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"269 ","pages":"Article 110354"},"PeriodicalIF":4.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynorphinergic lateral hypothalamus to posterior ventral tegmental area pathway matures after adolescence in male rats","authors":"Alexandra Rogers ,&nbsp;Emily M. Castro ,&nbsp;Shahrdad Lotfipour,&nbsp;Frances M. Leslie","doi":"10.1016/j.neuropharm.2025.110350","DOIUrl":"10.1016/j.neuropharm.2025.110350","url":null,"abstract":"<div><div>The highly plastic nature of the adolescent brain is well-known, and is thought to contribute to the unique susceptibility of adolescents to drugs of abuse. However, much investigation of adolescent plasticity has been focused on synaptic plasticity, as synapses are strengthened and pruned. Here, we show that dynorphin⁺ neurons in the lateral hypothalamus of adolescent male rats do not respond to low doses of intravenous combined nicotine + ethanol, while male adult lateral hypothalamus dynorphin⁺ neurons do. We also provide evidence that the dynorphinergic projection from the lateral hypothalamus to the posterior ventral tegmental area is not present in adolescent males, suggesting that axons are still extending during this time. Together, these results suggest a mechanism for the increased susceptibility of adolescent male rats to drug reward.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"270 ","pages":"Article 110350"},"PeriodicalIF":4.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroscience in Ukraine, past and present","authors":"Dmitri A. Rusakov ,&nbsp;Alexei Verkhratsky","doi":"10.1016/j.neuropharm.2025.110353","DOIUrl":"10.1016/j.neuropharm.2025.110353","url":null,"abstract":"","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"269 ","pages":"Article 110353"},"PeriodicalIF":4.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term folic acid treatment relieves chronic inflammatory pain and pain-induced anxiety by reducing MMP2 expression in rats","authors":"Wen-Hui Ni ,&nbsp;Ke Wang ,&nbsp;Yun Wang ,&nbsp;Jia Lu ,&nbsp;Chun-Ting Lu ,&nbsp;Wen Rong ,&nbsp;Yi-Feng Gu ,&nbsp;Wen-Juan Qian ,&nbsp;Hai-Long Zhang","doi":"10.1016/j.neuropharm.2025.110352","DOIUrl":"10.1016/j.neuropharm.2025.110352","url":null,"abstract":"<div><div>Chronic inflammatory pain is a top priority for arthritis patients seeking medical care. Despite the availability of NSAIDs and glucocorticoids, pain management becomes increasingly challenging due to central and peripheral sensitization. Previous studies have shown that Matrix metalloproteinase 2 (MMP2) promotes neuroinflammation by cleaving extracellular matrix proteins and activating pro-inflammatory cytokines. Folic acid acts as a promising candidate for the treatment of neuroinflammatory diseases due to its neuroprotective effects. However, the role of folic acid in inflammatory pain remains unclear. This study investigated the analgesic mechanisms of folic acid in inflammatory pain. Adult rats underwent inflammatory pain by injecting complete freund's adjuvant (CFA) into the right hindpaw. Behavioral tests were used to assess the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). The results demonstrated that CFA injection induced abnormal mechanical and thermal pain and increased MMP2 expression in L3-L5 DRG and SDH of CFA rats. MMP2 was mainly expressed in neurons rather than glial cells in L3-L5 DRG of CFA rats. We further discovered that MMP2 inhibitor auraptene or knockdown alleviated inflammatory pain in CFA rats. Interestingly, we observed that long-term folic acid treatment reversed MMP2 overexpression, resulting in sustained relief of chronic inflammatory pain. Consistently, long-term folic acid treatment also relieved pain-induced anxiety. These results indicated that folic acid had a protective role in chronic inflammatory pain and pain-induced anxiety by repressing MMP2 expression. Folic acid or auraptene might be promising therapeutic options for the treatment of chronic inflammatory pain.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"269 ","pages":"Article 110352"},"PeriodicalIF":4.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic insights into positive allosteric modulator and agonist using Gaussian accelerated and tau random acceleration simulations in the metabotropic glutamate receptor 2","authors":"Baoyu He ,&nbsp;Longfei Mao ,&nbsp;Lili Xi ,&nbsp;Jingjing Guo","doi":"10.1016/j.neuropharm.2025.110351","DOIUrl":"10.1016/j.neuropharm.2025.110351","url":null,"abstract":"<div><div>Schizophrenia is a severe brain disorder that usually produces a lifetime of disability. Related research shows activating metabotropic glutamate receptors holds therapeutic potential. Agonist-positive allosteric modulations (ago-PAMs) not only activate metabotropic glutamate receptors but also enhance glutamate-induced responses, offering a promising treatment strategy. However, the molecular mechanisms by which ago-PAM enhances glutamate-induced responses remain unclear, as does the potential influence of glutamate on ago-PAM. In this study, Gaussian accelerated molecular dynamics and tau random acceleration molecular dynamics simulations were employed to investigate the molecular mechanism between ago-PAM and glutamate in full-length mGlu₂. Results suggest that the ago-PAM JNJ-46281222 enhances the binding affinity and residence time of glutamates in the Venus flytrap (VFT) domains by initiating a variant reverse communication from the heptahelical transmembrane (7TM) domains to VFTs via the cysteine-rich domains. Meanwhile, glutamate facilitates the interaction between Trp676 and Glu701 to further induce the relaxation of TM5, promoting the opening of the PAM-binding pocket. Glutamate can also promote the upward rotation of the cyclopropylmethyl group of the JNJ-46281222 to bring the TM6-TM6 distance closer. Nevertheless, it remains uncertain how the binding between mGlu₂ and G protein differs when induced by small molecules binding in allosteric sites, orthosteric sites, or both. In conclusion, this study shed new light on the positive coordination relationship between ago-PAM and glutamate in the full-length mGlu₂ receptor, which could help develop novel and more effective ago-PAM to treat schizophrenia.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"269 ","pages":"Article 110351"},"PeriodicalIF":4.6,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effort-related motivational effects of methylphenidate: Reversal of the low-effort bias induced by tetrabenazine and enhancement of progressive ratio responding in male and female rats","authors":"Alev Ecevitoglu ,&nbsp;Renee A. Rotolo ,&nbsp;Gayle A. Edelstein ,&nbsp;Alexandra Goldhamer ,&nbsp;Matthew Mitola ,&nbsp;Rose E. Presby ,&nbsp;Abigail Yu ,&nbsp;Deanna Pietrorazio ,&nbsp;Emma Zorda ,&nbsp;Merce Correa ,&nbsp;John D. Salamone","doi":"10.1016/j.neuropharm.2025.110345","DOIUrl":"10.1016/j.neuropharm.2025.110345","url":null,"abstract":"<div><div>Dopamine (DA) regulates behavioral activation and effort-related aspects of motivation. Blockade of DA storage by tetrabenazine (TBZ) induces depressive symptoms in humans, including fatigue and apathy. TBZ shifts choice behavior in rodents from high-effort to low-effort options, which can be used to model motivational symptoms observed in psychiatric disorders. The catecholamine transport inhibitor methylphenidate (MPH) reverses the effort-related effects of TBZ in male rats, but this effect needs to be investigated in females. The current study examined the effects of MPH on effort-based choice in male and female rats. Animals were tested on the fixed ratio 5 (FR5)/chow feeding choice task. Because of sex differences in the effects of TBZ, 1.0 mg/kg was used in males, while 2.0 mg/kg was used in females. In both sexes, TBZ shifted choice from lever pressing to chow intake. Co-administration of MPH reversed the effort-related effects of TBZ in males at all doses tested (0.5–4.0 mg/kg IP), whereas only 1.0 and 2.0 mg/kg MPH reversed the effects of TBZ in females. Rats also were tested on a progressive ratio (PROG) schedule and a PROG/chow feeding choice task to assess the effects of MPH administered alone (0.5–4.0 mg/kg IP). MPH increased high-effort PROG responding on both tasks in males, whereas females showed no significant increase in lever pressing across the dose range tested. Investigating sex differences in the pharmacology and neurochemistry of effort-based choice enhances our understanding of sex as a factor in motivational dysfunctions, and may foster the development of treatments for effort-related psychiatric symptoms.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"269 ","pages":"Article 110345"},"PeriodicalIF":4.6,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Memory enhancement by unconditioned and conditioned heroin withdrawal: Role of corticotropin-releasing factor in the central amygdala","authors":"Nana Baidoo ,&nbsp;Aiden Shaver ,&nbsp;Brooke Ginson ,&nbsp;Julia Castellani ,&nbsp;Thomas Lapointe ,&nbsp;Michael Wolter ,&nbsp;Francesco Leri","doi":"10.1016/j.neuropharm.2025.110341","DOIUrl":"10.1016/j.neuropharm.2025.110341","url":null,"abstract":"<div><div>To test the hypothesis that unconditioned and conditioned opioid withdrawal enhance memory consolidation through shared neurobiological mechanisms, the current study focused on the central amygdala (CeA) and local corticotropin-releasing factor (CRF) neurotransmission. In the unconditioned withdrawal experiments, male Sprague-Dawley rats were implanted with subcutaneous osmotic mini-pumps releasing 3.5 mg/kg/day heroin (or sham surgery) and injected with 3 mg/kg naloxone (NLX) to precipitate withdrawal. In the conditioned withdrawal experiments, rats injected with heroin (2 mg/kg x 2 injections) received 3 mg/kg NLX immediately prior to confinement to one compartment (CS+) of a place conditioning apparatus, or vehicle prior to confinement in the alternative compartment (CS-). Using immunohistochemistry, it was established that both precipitated withdrawal and confinement to the withdrawal-paired CS + compartment elevated c-Fos expression within the CeA. More importantly, using the post-training approach to target consolidation of object memory, it was found that intra-CeA infusions of the CRF1 receptor antagonist ANT (0.2–2 μg/inf) blocked the memory-enhancing effects of both precipitated withdrawal and exposure to the withdrawal-paired CS + compartment. These findings indicate that pharmacological and conditioned opioid withdrawal influence memory consolidation through a common CRF-mediated mechanism within the CeA.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"269 ","pages":"Article 110341"},"PeriodicalIF":4.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behavioral manifestations and neural mechanisms of empathic pain","authors":"Siqi Yang ,&nbsp;Jiahui Zhang ,&nbsp;Qi Zhang ,&nbsp;Suwan Hu ,&nbsp;Yawei Ji ,&nbsp;Xiaokai Zhou ,&nbsp;Yinbing Pan ,&nbsp;Yuanyuan Wang","doi":"10.1016/j.neuropharm.2025.110344","DOIUrl":"10.1016/j.neuropharm.2025.110344","url":null,"abstract":"<div><div>Empathy is an important trait that allows individuals to comprehend and share the emotions and sentiments of others. It not only facilitates effective interpersonal communication, but also helps in establishing meaningful connections and fostering trust and understanding. Impaired empathy development can manifest as excessive self-centeredness, extreme egoism, and antisocial behaviors. Many psychiatric disorders, such as autism, narcissistic personality disorder, and schizophrenia, are often accompanied by empathy disorders. Pain empathy, which is a common behavioral paradigm of empathic behavior, is not only observed in humans but also in animals. By delving into the study of pain empathy, we can gain a deeper understanding of empathy itself. This understanding not only contributes to the advancement of scientific, clinical, and social fields, but also promotes the cultivation of emotional resonance and social harmony among humans, with profound significance and impact. This article provides a brief overview of the current understanding and mechanistic studies of pain empathy, as well as suggests future research directions.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"269 ","pages":"Article 110344"},"PeriodicalIF":4.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific signatures of GLP-1 and amylin on resting state brain activity and functional connectivity in awake rats","authors":"Tanzil M. Arefin ,&nbsp;Stina Börchers ,&nbsp;Doris Olekanma ,&nbsp;Samuel R. Cramer ,&nbsp;Morgan R. Sotzen ,&nbsp;Nanyin Zhang ,&nbsp;Karolina P. Skibicka","doi":"10.1016/j.neuropharm.2025.110348","DOIUrl":"10.1016/j.neuropharm.2025.110348","url":null,"abstract":"<div><div>Gut-produced glucagon-like peptide-1 (GLP-1) and pancreas-made amylin robustly reduce food intake by directly or indirectly affecting brain activity. While for both peptides a direct action in the hindbrain and the hypothalamus is likely, few studies examined their impact on whole brain activity in rodents and did so evaluating male rodents under anesthesia. However, both sex and anesthesia may significantly alter the influence of feeding controlling molecules on brain activity. Therefore, we investigated the effect of GLP-1 and amylin on brain activity and functional connectivity (FC) in awake adult male and female rats using resting-state functional magnetic resonance imaging (rsfMRI). We further examined the relationship between the altered brain activity or connectivity and subsequent food intake in response to amylin or GLP-1. We observed sex divergent effects of amylin and GLP-1 on the brain activity and FC patterns. Most importantly correlation analysis between FC and feeding behavior revealed that different brain areas potentially drive reduced food intake in male and female rats. Our findings underscore the distributed and distinctly sex divergent neural network engaged by each of these anorexic peptides and suggest that different brain areas may be the primary drivers of the feeding outcome in male and female rats. Moreover, prominent activity and connectivity alterations observed in brain areas not typically associated with feeding behavior in both sexes may either indicate novel feeding centers or alternatively suggest the involvement of these substances in behaviors beyond feeding and metabolism. The latter question is of potential translational significance as analogues of both amylin and GLP-1 are clinically utilized.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"269 ","pages":"Article 110348"},"PeriodicalIF":4.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural mechanisms, influencing factors and interventions in empathic pain","authors":"Furui Liu,&nbsp;Ziwan He,&nbsp;Yongjie Wang","doi":"10.1016/j.neuropharm.2025.110349","DOIUrl":"10.1016/j.neuropharm.2025.110349","url":null,"abstract":"<div><div>Empathic pain, defined as the emotional resonance with the suffering of others, is akin to the observer's own experience of pain and is vital for building and sustaining positive interpersonal relationships. Despite its importance, the neural mechanism of empathic pain remains poorly understood. In this review, we integrated and summarized the currently knowledge on the neural networks associated with empathic pain, focusing on key brain regions such as the insula, anterior cingulate cortex (ACC), ventral tegmental area (VTA), nucleus accumbens (NAc), and locus coeruleus (LC)/norepinephrine (NE)-sympatho-adrenomedullar (LC/NE-SAM) system. We also reviewed the factors that affect empathic pain, including gender, personal beliefs, the intimacy of relationships, and the nature of interpersonal relationships, and highlighted the central role of the insula and ACC in the neural circuitry of empathy, the importance of the IC-BLA and ACC-NAc/VTA connections in modulating empathic pain, and the involvement of the LC/NE-SAM system in mediating pain empathy. We further discussed how gender significantly influences empathic pain, with women showing more intense emotional reactions to social distress than men. It also summarized the roles of personal pain history and empathy levels in modulating empathic responses. Furthermore, the review emphasized the impact of social factors such as the nature of interpersonal relationships and experiences of social exclusion on empathic pain. By providing a detailed exploration of the neural mechanisms and influencing factors of empathic pain, this review aims to establish a robust foundation for developing targeted therapeutic strategies and improving pain management in clinical settings.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"269 ","pages":"Article 110349"},"PeriodicalIF":4.6,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}