NeuropharmacologyPub Date : 2024-08-06DOI: 10.1016/j.neuropharm.2024.110098
Kathryn R. Przybysz, Joel E. Shillinglaw, Shannon R. Wheeler, Elizabeth J. Glover
{"title":"Chronic ethanol exposure produces long-lasting, subregion-specific physiological adaptations in RMTg-projecting mPFC neurons","authors":"Kathryn R. Przybysz, Joel E. Shillinglaw, Shannon R. Wheeler, Elizabeth J. Glover","doi":"10.1016/j.neuropharm.2024.110098","DOIUrl":"10.1016/j.neuropharm.2024.110098","url":null,"abstract":"<div><p>Chronic ethanol exposure produces neuroadaptations in the medial prefrontal cortex (mPFC) that are thought to facilitate maladaptive behaviors that interfere with recovery from alcohol use disorder. Despite evidence that different cortico-subcortical projections play distinct roles in behavior, few studies have examined the physiological effects of chronic ethanol at the circuit level. The rostromedial tegmental nucleus (RMTg) is functionally altered by chronic ethanol exposure. Our recent work identified dense input from the mPFC to the RMTg, yet the effects of chronic ethanol exposure on this circuitry is unknown. In the current study, we examined physiological changes after chronic ethanol exposure in prelimbic (PL) and infralimbic (IL) mPFC neurons projecting to the RMTg. Adult male Long-Evans rats were injected with fluorescent retrobeads into the RMTg and rendered dependent using a 14-day chronic intermittent ethanol (CIE) vapor exposure paradigm. Whole-cell patch-clamp electrophysiological recordings were performed in fluorescently-labeled (RMTg-projecting) and -unlabeled (projection-undefined) layer 5 pyramidal neurons 7–10 days following ethanol exposure. CIE exposure significantly increased intrinsic excitability as well as spontaneous excitatory and inhibitory postsynaptic currents (sE/IPSCs) in RMTg-projecting IL neurons. In contrast, no lasting changes in excitability were observed in RMTg-projecting PL neurons, although a CIE-induced reduction in excitability was observed in projection-undefined PL neurons. CIE exposure also increased the frequency of sEPSCs in RMTg-projecting PL neurons. These data uncover novel subregion- and circuit-specific neuroadaptations in the mPFC following chronic ethanol exposure and reveal that the IL mPFC-RMTg projection is uniquely vulnerable to long-lasting effects of chronic ethanol exposure.</p></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"259 ","pages":"Article 110098"},"PeriodicalIF":4.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0028390824002673/pdfft?md5=7da4ba77855734202fa20317a679900f&pid=1-s2.0-S0028390824002673-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907225","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}
NeuropharmacologyPub Date : 2024-08-05DOI: 10.1016/j.neuropharm.2024.110099
María C. Gutiérrez , María C. Perondi , Gisella L. Tortoni , Andrea B. Cragnolini , Gabriel R. Cuadra , Analía Valdomero
{"title":"Early protein restriction in rats induces anhedonia in adult offspring: A key role of BDNF-TrkB signaling in the nucleus accumbens shell","authors":"María C. Gutiérrez , María C. Perondi , Gisella L. Tortoni , Andrea B. Cragnolini , Gabriel R. Cuadra , Analía Valdomero","doi":"10.1016/j.neuropharm.2024.110099","DOIUrl":"10.1016/j.neuropharm.2024.110099","url":null,"abstract":"<div><p>Clinical evidence suggests that early malnutrition promotes symptoms related to psychiatric disorders later in life. Nevertheless, the molecular mechanisms underpinning nutritional injury induce depression remains unknown. The purpose of the present study was to evaluate whether perinatal protein restriction increases vulnerability to developing depressive-like behavior in adulthood by focusing on anhedonia, a core symptom of depression. To this, male adult Wistar rats submitted to a protein restriction schedule at perinatal age (PR-rats), were subjected to the sucrose preference test (SPT), the novel object recognition test (NORT), the forced swim test (FST), and the elevated plus maze (EPM), and compared to animals fed with a normoprotein diet. To investigate neurobiological substrates linked to early protein undernutrition-facilitated depressive-like behavior, we assessed the levels of brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the nucleus accumbens (NAc), and evaluated the reversal of anhedonic-like behavior by infusing ANA-12. We found that early malnutrition decreased sucrose preference, impaired performance in the NORT and increased immobility time in the FST. Furthermore, perinatal protein-restriction-induced anhedonia correlated with increased BDNF and p-TrkB protein levels in the NAc, a core structure in the reward circuit linked with anhedonia. Finally, bilateral infusion of the TrkB antagonist ANA-12 into the NAc shell ameliorated a reduced sucrose preference in the PR-rats.</p><p>Altogether, these findings revealed that protein restriction during pregnancy and lactation facilitates depressive-like behavior later in life and may increase the risk of developing anhedonia by altering BDNF-TrkB in the NAc shell.</p></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"258 ","pages":"Article 110099"},"PeriodicalIF":4.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889796","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}
NeuropharmacologyPub Date : 2024-07-31DOI: 10.1016/j.neuropharm.2024.110097
Geovana Rosa Oliveira dos Santos , Marina Minto Cararo-Lopes , Isabela Ribeiro Possebom , Larissa de Sá Lima , Cristoforo Scavone , Elisa Mitiko Kawamoto
{"title":"Sex-dependent changes in AMPAR expression and Na, K-ATPase activity in the cerebellum and hippocampus of α-Klotho-Hypomorphic mice","authors":"Geovana Rosa Oliveira dos Santos , Marina Minto Cararo-Lopes , Isabela Ribeiro Possebom , Larissa de Sá Lima , Cristoforo Scavone , Elisa Mitiko Kawamoto","doi":"10.1016/j.neuropharm.2024.110097","DOIUrl":"10.1016/j.neuropharm.2024.110097","url":null,"abstract":"<div><p>Aging is characterized by a functional decline in several physiological systems. α-Klotho-hypomorphic mice (Kl<sup>−/−</sup>) exhibit accelerated aging and cognitive decline. We evaluated whether male and female α-Klotho-hypomorphic mice show changes in the expression of synaptic proteins, N-methyl-<span>d</span>-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits, postsynaptic density protein 95 (PSD-95), synaptophysin and synapsin, and the activity of Na<sup>+</sup>, K<sup>+</sup>-ATPase (NaK) isoforms in the cerebellum and hippocampus. In this study, we demonstrated that in the cerebellum, Kl<sup>−/−</sup> male mice have reduced expression of GluA1 (AMPA) compared to wild-type (Kl<sup>+/+</sup>) males and Kl<sup>−/−</sup> females. Also, Kl−/− male and female mice show reduced ɑ2/ɑ3-NaK and Mg<sup>2+</sup>-ATPase activities in the cerebellum, respectively, and sex-based differences in NaK and Mg<sup>2+</sup>-ATPase activities in both the regions. Our findings suggest that α-Klotho could influence the expression of AMPAR and the activity of NaK isoforms in the cerebellum in a sex-dependent manner, and these changes may contribute, in part, to cognitive decline.</p></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"258 ","pages":"Article 110097"},"PeriodicalIF":4.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879190","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}
NeuropharmacologyPub Date : 2024-07-31DOI: 10.1016/j.neuropharm.2024.110094
Igor Manzhulo, Anna Tyrtyshnaia, Anastasia Egoraeva, Darya Ivashkevich, Alexander Girich, Olga Manzhulo
{"title":"Anti-inflammatory and anti-apoptotic activity of synaptamide improves the morphological state of neurons in traumatic brain injury","authors":"Igor Manzhulo, Anna Tyrtyshnaia, Anastasia Egoraeva, Darya Ivashkevich, Alexander Girich, Olga Manzhulo","doi":"10.1016/j.neuropharm.2024.110094","DOIUrl":"10.1016/j.neuropharm.2024.110094","url":null,"abstract":"<div><p>Traumatic brain injuries (TBI) of varying severity are becoming more frequent all over the world. The process of neuroinflammation, in which macrophages and microglia are key players, underlies all types of brain damage. The present study focuses on evaluating the therapeutic potential of N-docosahexaenoylethanolamine (DHEA, synaptamide), which is an endogenous metabolite of docosahexaenoic acid in traumatic brain injury. Previously, several <em>in vitro</em> and <em>in vivo</em> models have shown significant <em>anti</em>-neuroinflammatory and synaptogenic activity of synaptamide. The results of the present study show that synaptamide by subcutaneous administration (10 mg/kg/day, 7 days) exerts anti-inflammatory and anti-apoptotic effects in the thalamus and cerebral cortex of experimental animals (male C57BL/6 mice). Were analyzed the dynamics of changes in the activity of Iba-1- and CD68-positive microglia/macrophages, the level of production of pro-inflammatory cytokines (IL1β, IL6, TNFα) and pro-apoptotic proteins (Bad, Bax), the expression of pro- and anti-inflammatory markers (<em>CD68, CD206, arg-1</em>). ATF3 transcription factor distribution and neuronal state in the thalamus and cerebral cortex of animals with craniotomy, traumatic brain injury, and therapy are quantitatively assessed. The obtained data showed that synaptamide: (1) has no effect on the total pool of microglia/macrophages; (2) inhibits the activity of pro-inflammatory microglia/macrophages and cytokines they produce; (3) increases the expression of <em>CD206</em> but not <em>arg-1</em>; (4) has anti-apoptotic effect and (5) improves the morphological state of neurons. The results obtained confirm the high therapeutic potential of synaptamide in the therapy of traumatic brain injury.</p></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"258 ","pages":"Article 110094"},"PeriodicalIF":4.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879189","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}
NeuropharmacologyPub Date : 2024-07-30DOI: 10.1016/j.neuropharm.2024.110095
Joanna Medina , Rose M. De Guzman , Joanna L. Workman
{"title":"Prolactin mitigates chronic stress-induced maladaptive behaviors and physiology in ovariectomized female rats","authors":"Joanna Medina , Rose M. De Guzman , Joanna L. Workman","doi":"10.1016/j.neuropharm.2024.110095","DOIUrl":"10.1016/j.neuropharm.2024.110095","url":null,"abstract":"<div><p>Stress is a major risk factor for several neuropsychiatric disorders in women, including postpartum depression. During the postpartum period, diminished ovarian hormone secretion increases susceptibility to developing depressive symptoms. Pleiotropic peptide hormones, like prolactin, are markedly released during lactation and suppress hypothalamic-pituitary-adrenal axis responses in women and acute stress-induced behavioral responses in female rodents. However, the effects of prolactin on chronic stress-induced maladaptive behaviors remain unclear. Here, we used chronic variable stress to induce maladaptive physiology in ovariectomized female rats and concurrently administered prolactin to assess its effects on several depression-relevant behavioral, endocrine, and neural characteristics. We found that chronic stress increased sucrose anhedonia and passive coping in saline-treated, but not prolactin-treated rats. Prolactin treatment did not alter stress-induced thigmotaxis, corticosterone (CORT) concentrations, hippocampal cell activation or survival. However, prolactin treatment reduced basal CORT concentrations and increased dopaminergic cells in the ventral tegmental area. Further, prolactin-treated rats had reduced microglial activation in the ventral hippocampus following chronic stress exposure. Together, these data suggest prolactin mitigates chronic stress-induced maladaptive behaviors and physiology in hypogonadal females. Moreover, these findings imply neuroendocrine-immune mechanisms by which peptide hormones confer stress resilience during periods of low ovarian hormone secretion.</p></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"258 ","pages":"Article 110095"},"PeriodicalIF":4.6,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796101","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}
NeuropharmacologyPub Date : 2024-07-29DOI: 10.1016/j.neuropharm.2024.110096
Akshatha P. Kamath , Pawan Ganesh Nayak , Jeena John , Srinivas Mutalik , Ashok Kumar Balaraman , Nandakumar Krishnadas
{"title":"Revolutionizing neurotherapeutics: Nanocarriers unveiling the potential of phytochemicals in Alzheimer's disease","authors":"Akshatha P. Kamath , Pawan Ganesh Nayak , Jeena John , Srinivas Mutalik , Ashok Kumar Balaraman , Nandakumar Krishnadas","doi":"10.1016/j.neuropharm.2024.110096","DOIUrl":"10.1016/j.neuropharm.2024.110096","url":null,"abstract":"<div><p>Neurological disorders pose a huge worldwide challenge to the healthcare system, necessitating innovative strategies for targeted drug delivery to the central nervous system. Alzheimer's disease (AD) is an untreatable neurodegenerative condition characterized by dementia and alterations in a patient's physiological and mental states. Since ancient times, medicinal plants have been an important source of bioactive phytochemicals with immense therapeutic potential. This review investigates new and safer alternatives for prevention and treatment of disease related to inevitable side effects associated with synthetic compounds. This review examines how nanotechnology can help in enhancing the delivery of neuroprotective phytochemicals in AD. Nevertheless, despite their remarkable neuroprotective properties, these natural products often have poor therapeutic efficacy due to low bioavailability, limited solubility and imperfect blood brain barrier (BBB) penetration. Nanotechnology produces personalized drug delivery systems which are necessary for solving such problems. In overcoming these challenges, nanotechnology might be employed as a way forward whereby customized medication delivery systems would be established as a result. The use of nanocarriers in the design and application of important phytochemicals is highlighted by this review, which indicate potential for revolutionizing neuroprotective drug delivery. We also explore the complications and possibilities of using nanocarriers to supply nutraceuticals and improve patients' standard of living, and preclinical as well as clinical investigations displaying that these techniques are effective in mitigating neurodegenerative diseases. In order to fight brain diseases and improve patient's health, scientists and doctors can employ nanotechnology with its possible therapeutic interventions.</p></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"259 ","pages":"Article 110096"},"PeriodicalIF":4.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S002839082400265X/pdfft?md5=b481825937c5f34755145dc4c482c9ce&pid=1-s2.0-S002839082400265X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796375","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}
NeuropharmacologyPub Date : 2024-07-25DOI: 10.1016/j.neuropharm.2024.110092
Michaela G. Kaoullas, David M. Thal, Arthur Christopoulos, Celine Valant
{"title":"Ligand bias at the muscarinic acetylcholine receptor family: Opportunities and challenges","authors":"Michaela G. Kaoullas, David M. Thal, Arthur Christopoulos, Celine Valant","doi":"10.1016/j.neuropharm.2024.110092","DOIUrl":"10.1016/j.neuropharm.2024.110092","url":null,"abstract":"<div><p>Muscarinic acetylcholine receptors (mAChRs) are G protein-coupled receptors (GPCRs) that are activated by the endogenous neurotransmitter, acetylcholine (ACh). Disruption of mAChR signalling has been associated with a variety of neurological disorders and non-neurological diseases. Consequently, the development of agonists and antagonists of the mAChRs has been a major avenue in drug discovery. Unfortunately, mAChR ligands are often associated with on-target side effects for two reasons. The first reason is due to the high sequence conservation at the orthosteric ACh binding site among all five receptor subtypes (M<sub>1</sub>-M<sub>5</sub>), making on-target subtype selectivity a major challenge. The second reason is due to on-target side effects of mAChR drugs that are associated with the pleiotropic nature of mAChR signalling at the level of a single mAChR subtype. Indeed, there is growing evidence that within the myriad of signalling events produced by mAChR ligands, some will have therapeutic benefits, whilst others may promote cholinergic side effects. This paradigm of drug action, known as ligand bias or biased agonism, is an attractive feature for next-generation mAChR drugs, as it holds the promise of developing drugs devoid of on-target adverse effects. Although relatively simple to detect and even quantify <em>in vitro</em>, ligand bias, as observed in recombinant systems, does not always translate to <em>in vivo</em> systems, which remains a major hurdle in GPCR drug discovery, including the mAChR family. Here we report recent studies that have attempted to detect and quantify ligand bias at the mAChR family, and briefly discuss the challenges associated with biased agonist drug development.</p><p>This article is part of the Special Issue on “Ligand Bias”.</p></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"258 ","pages":"Article 110092"},"PeriodicalIF":4.6,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0028390824002612/pdfft?md5=6071bbb14f75102f403ee1c085e918e4&pid=1-s2.0-S0028390824002612-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788671","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}
NeuropharmacologyPub Date : 2024-07-25DOI: 10.1016/j.neuropharm.2024.110091
Yuchun Cao , Jiahui Zhang , Xiaofang He , Chenye Wu , Zeyuan Liu , Bin Zhu , Liying Miao
{"title":"Empathic pain: Exploring the multidimensional impacts of biological and social aspects in pain","authors":"Yuchun Cao , Jiahui Zhang , Xiaofang He , Chenye Wu , Zeyuan Liu , Bin Zhu , Liying Miao","doi":"10.1016/j.neuropharm.2024.110091","DOIUrl":"10.1016/j.neuropharm.2024.110091","url":null,"abstract":"<div><p>Empathic pain refers to an individual's perception, judgment, and emotional response to others' pain. This complex social cognitive ability is crucial for healthy interactions in human society. In recent years, with the development of multidisciplinary research in neuroscience, psychology and sociology, empathic pain has become a focal point of widespread attention in these fields. However, the neural mechanism underlying empathic pain remain a controversial and unresolved area. This review aims to comprehensively summarize the history, influencing factors, neural mechanisms and pharmacological interventions of empathic pain. We hope to provide a comprehensive scientific perspective on how humans perceive and respond to others' pain experiences and to provide guidance for future research directions and clinical applications.</p><p>This article is part of the Special Issue on “Empathic Pain”.</p></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"258 ","pages":"Article 110091"},"PeriodicalIF":4.6,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141766842","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}
NeuropharmacologyPub Date : 2024-07-25DOI: 10.1016/j.neuropharm.2024.110093
Samuel Singleton , Clara Dieterle , David J. Walker , Tyko Runeberg , Andrew S. Oswald , Greta Rosenqvist , Laura Robertson , Taylor McCarthy , Shuvam Sarkar , Daniel Baptista-Hon , Tim G. Hales
{"title":"Activation of μ receptors by SR-17018 through a distinctive mechanism","authors":"Samuel Singleton , Clara Dieterle , David J. Walker , Tyko Runeberg , Andrew S. Oswald , Greta Rosenqvist , Laura Robertson , Taylor McCarthy , Shuvam Sarkar , Daniel Baptista-Hon , Tim G. Hales","doi":"10.1016/j.neuropharm.2024.110093","DOIUrl":"10.1016/j.neuropharm.2024.110093","url":null,"abstract":"<div><p>Agonists at μ opioid receptors relieve acute pain, however, their long-term use is limited by side effects, which may involve β-arrestin2. Agonists biased against β-arrestin2 recruitment may be advantageous. However, the classification of bias may be compromised by assays utilising overexpressed μ receptors which overestimate efficacy for G-protein activation. There is a need for re-evaluation with restricted receptor availability to determine accurate agonist efficacies. We depleted μ receptor availability in PathHunter CHO cells using the irreversible antagonist, β-funaltrexamine (β-FNA), and compared efficacies and apparent potencies of twelve agonists, including several previously reported as biased, in β-arrestin2 recruitment and cAMP assays. With full receptor availability all agonists had partial efficacy for stimulating β-arrestin2 recruitment relative to DAMGO, while only TRV130 and buprenorphine were partial agonists as inhibitors of cAMP accumulation. Limiting receptor availability by prior exposure to β-FNA (100 nM) revealed morphine, oxycodone, PZM21, herkinorin, U47700, tianeptine and U47931e are also partial agonists in the cAMP assay. The efficacies of all agonists, except SR-17018, correlated between β-arrestin2 recruitment and cAMP assays, with depleted receptor availability in the latter. Furthermore, naloxone and cyprodime exhibited non-competitive antagonism of SR-17018 in the β-arrestin2 recruitment assay. Limited antagonism by naloxone was also non-competitive in the cAMP assay, while cyprodime was competitive. Furthermore, SR-17018 only negligibly diminished β-arrestin2 recruitment stimulated by DAMGO (1 μM), whereas fentanyl, morphine and TRV130 all exhibited the anticipated competitive inhibition. The data suggest that SR-17018 achieves bias against β-arrestin2 recruitment through interactions with μ receptors outside the orthosteric agonist site.</p></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"258 ","pages":"Article 110093"},"PeriodicalIF":4.6,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788726","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}
NeuropharmacologyPub Date : 2024-07-22DOI: 10.1016/j.neuropharm.2024.110087
Yuhui Deng , Xin Liang , Yue Li , Lin Jiang , Jin Wang , Jing Tang , Jing Li , Yuhan Xie , Kai Xiao , Peilin Zhu , Yijing Guo , Yanmin Luo , Yong Tang
{"title":"Corrigendum to “PGC-1α in the hippocampus mediates depressive-like and stress-coping behaviours and regulates excitatory synapses in the dentate gyrus in mice” [Neuropharmacology 250 (2024) 109908]","authors":"Yuhui Deng , Xin Liang , Yue Li , Lin Jiang , Jin Wang , Jing Tang , Jing Li , Yuhan Xie , Kai Xiao , Peilin Zhu , Yijing Guo , Yanmin Luo , Yong Tang","doi":"10.1016/j.neuropharm.2024.110087","DOIUrl":"10.1016/j.neuropharm.2024.110087","url":null,"abstract":"","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"258 ","pages":"Article 110087"},"PeriodicalIF":4.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0028390824002569/pdfft?md5=116201852b6a07bb29c0c5f81e6e3b8b&pid=1-s2.0-S0028390824002569-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752240","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}