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An 86-year-old male with multiple medical comorbidities was referred for an elective transcatheter aortic valve replacement (TAVR) for severe symptomatic aortic stenosis with an ejection fraction of 35%. A self-expanding valve was deployed successfully, but intraoperative transesophageal echocardiography (TEE) confirmed an acute type A aortic dissection (ATAAD), necessitating immediate intervention. Multiple intraoperative imaging modalities were utilized for deployment of a conformable GORE TAG (cTAG) stent graft for thoracic endovascular aortic repair (TEVAR). This case demonstrates TEVAR as an effective, minimally invasive option for immediate repair of ATAAD as a complication of TAVR in a high-risk surgical patient., Competing Interests: None., (© 2024 The Author(s).)

Faced with environmental changes, plants may either move to track their ancestral niches or evolve to adapt to new niches. Vitaceae, the grape family, has evolved diverse adaptive traits facilitating a global expansion in wide-ranging habitats, making it ideal for investigating transition between move and evolve strategies and exploring the underlying mechanisms. Here we inferred the patterns of biogeographic diversification and trait evolution in Vitaceae based on a robust phylogeny with dense sampling including 495 species (~52% of Vitaceae species). Vitaceae probably originated from Asia-the diversity centre of extant genera and the major source of dispersals. Boundaries of the Eocene, Oligocene and Miocene were identified as turning points in shifting strategies. A significant decrease in move strategy was identified during the Oligocene, followed by increases in move and evolve. After the Miocene, evolve began to dominate, during which increased niche opportunities and key trait innovations played important roles., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Stock price crash risk is of particular interest in developing countries as it poses a significant threat to investors and can have detrimental effects on the stability of emerging markets. This study investigates the role of financial flexibility in preventing stock price crash risk in the Vietnamese stock market, with a specific focus on the COVID-19 pandemic. Using the fixed-effect, system GMM, and quantile regression methods on a sample of 645 Vietnamese listed firms from 2011 to 2021, this study found that financial flexibility has a significant impact on preventing stock price crash risk. This effect was augmented during the COVID-19 crisis. Furthermore, this study found that financial flexibility mitigated the impact of the COVID-19 crisis on stock price crash risk. The findings provide important implications for firm regulators, shareholders, and investors to respond to similar future crises., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Intestinal obstruction due to ligament (fibrous band) arising from the top of Meckel's diverticulum is a rare cause. To date, in the world, only a few cases have been reported and there are not enough statistics on the incidence of this disease. This case presentation will help doctors working in the field of pediatric surgery or of pediatric imaging diagnosis have more experiences on diagnosis and treatment, and enrich the medical literature on this rare disease. We report a case of an 8-year-old boy with intestinal obstruction due to ligament arising from Meckel's diverticulum with complete data set such as clinical manifestations, imaging diagnosis (ultrasound, unprepared abdominal x-ray, computerized tomography scanner with contrast injection), surgical information, and histopathological findings. Intestinal obstruction due to the ligament arising from the apex of Meckel's diverticulum is an extremely rare disease and has asymptomatic imaging features so the preoperative diagnosis is only based on the indirect findings of computerized tomography scanner. The early diagnosis of an intestinal obstruction due to fibrous band can be made by using imaging methods such as ultrasound, unprepared abdominal x-ray, computerized tomography scanner with contrast injection, contributing to the prompt diagnosis in order to avoid serious complications including bowel necrosis, intestinal perforation, and perforated diverticulum., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Ruptured abdominal aortic aneurysm (RAAA) is an acute aortic condition that requires emergent intervention and appropriate continuity of care to optimize patient outcomes. We describe the standardized RAAA protocol at the Houston Methodist Hospital Acute Aortic Treatment Center, developed to navigate critical patient transfer periods safely and efficiently, make crucial decisions about surgical intervention, and clearly communicate these plans with other care team providers. Our workflow is organized into five phases: prehospital, preoperative, intraoperative, postoperative, and post-discharge. We identify the transfer center, anesthesia, operating room nursing staff, surgeons, and intensive care unit as key entities of our acute aortic pathology care team. This systematic protocol for the management of acute aortic emergencies such as RAAA identifies critical decision points, potential complications at each stage, and recommendations for best practice., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2023 The Author(s).)

This study investigated the impact of the COVID-19 crisis on firm risk and performance in different country-level governance qualities in the MENA region. Analyzing a sample of 739 non-financial listed firms in 12 MENA countries for the period 2011-2020, we found that the COVID-19 crisis negatively impacted the performance of firms, especially low-performance firms, in most industries, and increased firm risk in general. Moreover, we found that national governance quality plays an important role in mitigating the negative impact of the COVID-19 crisis on firm operations. Specifically, national governance quality reduces the negative impact of the COVID-19 crisis on firm performance and the positive impact of the crisis on firm risk. The results are consistent with our contention that national governance quality contributes to creating a positive environment for businesses activities and reducing economic shocks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Almustafa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study analyzes the effectiveness of bank risk management in ASEAN countries and examines the specific role of risk governance in enhancing a bank's risk management effectiveness. Our results show that the risk management effectiveness of banks in ASEAN countries is low. Furthermore, by focusing on the insolvency risk, credit risk, and operational risk management of banks in ASEAN countries, the dynamic panel models using the two-step GMM method provide evidence that risk governance structure and its effectiveness positively correlate with risk management effectiveness in banks. Based on our findings, the regulators can establish the guidelines related to risk governance to manage a bank's risk management activities and maintain bank stability., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

Novel N,C,S-TiO 2 /WO 3 /rGO Z scheme photocatalyst was successfully synthesized from graphite, TIOT, and ammonium metatungstate precursors. Material characteristics such as crystal structure, surface morphology, functional groups, specific surface area, elemental composition, band gap energy, and electron-hole recombination were characterized by XRD, TEM, BET, SEM/EDX, FT-IR, UV-VIS, and PL methods. The as-synthesized novel N,C,S-TiO 2 /WO 3 /rGO Z-scheme heterojunction photocatalyst exhibited visible light-driven photocatalytic activity (the band gap energy = 2.24 eV), could generate both effective electrons and holes, and presented the lowest electron-hole recombination rate compared to all individual components. Different factors impacting the photocatalytic decomposition of Direct Blue 71 (DB 71) by the N,C,S-TiO 2 /WO 3 /rGO system were studied. The results showed that pH of the solution, catalyst load, DB 71 initial concentration, and reaction time affected the DB 71 photocatalytic degradation efficiency. The DB 71 degradation completed after 100 min with a typical efficiency of over 91%, which was much better than other photocatalytic systems. The DB 71 degradation process followed the pseudo-first-order kinetics model with coefficients of determination > 0.95 for all conditions. The photocatalyst was easily regenerated, and exhibited a very good stability, with a photocatalytic degradation efficiency of over 83.0% after 3 cycles., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Biodiversity exchanges across the Malesian region, linking the distinct biotas of Asia and Australia, have long attracted the curiosity of biologists. Tetrastigma (Vitaceae) has a wide distribution in Asia through the Sunda archipelago to Australia and provides a good case to elucidate floristic exchange between Asia and Australia. Tetrastigma species have fleshy fruits that are consumed by birds, representing a lineage with a predictable dispersal across island chains. We herein estimate the divergence times and reconstruct the biogeographic history of Tetrastigma with intensive taxon sampling (96 of approximately 120 species; >80%) using 10 chloroplast loci. The biogeographic history of Tetrastigma was reconstructed with 4-area and 6-area divisions by delineating the Sunda region into one or three areas of endemism based on a phylogenetic bioregionalization analysis and the geological history of Malesia. The 4-area division shows that Tetrastigma originated in continental Asia and diverged from the recently segregated genus Pseudocayratia in the early Eocene (49.43 Ma). Dispersal from continental Asia might have started in the late Eocene but mainly occurred in the last 10 Myr. Continental Asia is indicated to be the most important source area while Sunda is the biggest sink, with 16 of the 27 dispersal events inferred from continental Asia to Sunda. Only seven dispersal events are inferred arriving in the Sahul plate and one reverse dispersal from Sahul back to Asia. The 6-area division suggests that the Philippines have been an active junction between Asia and Australia. The biogeographic history of Tetrastigma illustrates an asymmetric floristic exchange between Asia and Australia in this genus, which has been facilitated by the formation of terrestrial connections in the late Miocene and the expansion of wet tropical forests across Wallace's Line and beyond., (© 2021 Willi Hennig Society.)

High species diversity may result from recent rapid speciation in a 'cradle' and/or the gradual accumulation and preservation of species over time in a 'museum'. China harbours nearly 10% of angiosperm species worldwide and has long been considered as both a museum, owing to the presence of many species with hypothesized ancient origins, and a cradle, as many lineages have originated as recent topographic changes and climatic shifts-such as the formation of the Qinghai-Tibetan Plateau and the development of the monsoon-provided new habitats that promoted remarkable radiation. However, no detailed phylogenetic study has addressed when and how the major components of the Chinese angiosperm flora assembled to form the present-day vegetation. Here we investigate the spatio-temporal divergence patterns of the Chinese flora using a dated phylogeny of 92% of the angiosperm genera for the region, a nearly complete species-level tree comprising 26,978 species and detailed spatial distribution data. We found that 66% of the angiosperm genera in China did not originate until early in the Miocene epoch (23 million years ago (Mya)). The flora of eastern China bears a signature of older divergence (mean divergence times of 22.04-25.39 Mya), phylogenetic overdispersion (spatial co-occurrence of distant relatives) and higher phylogenetic diversity. In western China, the flora shows more recent divergence (mean divergence times of 15.29-18.86 Mya), pronounced phylogenetic clustering (co-occurrence of close relatives) and lower phylogenetic diversity. Analyses of species-level phylogenetic diversity using simulated branch lengths yielded results similar to genus-level patterns. Our analyses indicate that eastern China represents a floristic museum, and western China an evolutionary cradle, for herbaceous genera; eastern China has served as both a museum and a cradle for woody genera. These results identify areas of high species richness and phylogenetic diversity, and provide a foundation on which to build conservation efforts in China.

Tetrastigma (Miq.) Planch. is one of the most species-rich genera of the economically and agronomically important grape family Vitaceae. It includes ca. 95 species widely distributed in the tropics and subtropics of Asia and Australia. Species of Tetrastigma exhibit great diversity in both vegetative and reproductive characters. Here we inferred a well-supported phylogeny of Tetrastigma based on ten chloroplast DNA regions with an expanded taxon sampling of 72 species and two varieties. Our molecular results support six major clades within Tetrastigma and the relationships among these clades were well-resolved. We also documented seed morphology of 44 species covering the six major clades of the genus. Ancestral states of eight characters (seed shape, seed surface rumination pattern, chalaza length/width ratio, chalaza position, ventral infold position, ventral infold divergence, ventral infold depth in cross section, and endosperm shape) were reconstructed in Mesquite and R with four models. Character optimizations suggest that all character states have evolved multiple times except that the irregular-shaped surface rumination has derived only once in Tetrastigma . We evaluated the taxonomic importance of seed morphology and identified potential morphological evidence to support each major clade. Our comprehensive analyses of Tetrastigma shed insights into the infrageneric classification of this morphologically diverse and ecologically important genus in tropical and subtropical Asia.

Two Gram-stain-positive strains, VE80T and VE116, which were resistant to vancomycin, were isolated from retail chicken meat and liver in Ho Chi Minh, Vietnam, respectively. These strains were characterized by sequence analyses of 16S rRNA, RNA polymerase α-subunit (rpoA), ATP synthase α-subunit (atpA), and phenylalanyl-tRNA synthase α-subunit (pheS) genes, determination of DNA G+C content, cellular fatty acid methyl ester analysis, DNA-DNA hybridization, and conventional morphological and biochemical tests. Strains VE80T and VE116 had 99.6 % 16S rRNA gene sequence similarity with Enterococcus canintestini LMG 13590T, and 99.1 % 16S rRNA gene sequence similarity with Enterococcus dispar ATCC 51266T. However, the two isolates could be clearly differentiated from these reference strains by the low sequence similarities (86.1-86.8 %) of the atpA gene, low DNA-DNA relatedness (<22.8 %), and differences in the production of acid from melezitose and methyl α-d-glucoside. Based on the results obtained in the present study, these two isolates are considered to represent a novel species of the genus Enterococcus, for which the name Enterococcus saigonensis sp. nov., is proposed. The type strain is VE80T (=JCM 31193T=CCUG 68827T).

To investigate the microbial quality of retail pepper in Vietnam, the enumeration and detection of Enterobacteriaceae and the screening of cefotaxime (CTX)-resistant coliforms were performed by using 84 commercial samples. Although Enterobacteriaceae were isolated from 78 samples, the number of Enterobacteriaceae was lower than 1.0 log CFU/g in 46 samples. For the detection of Enterobacteriaceae with the International Organization for Standardization methods, Salmonella spp., Escherichia coli, Klebsiella pneumoniae, Cronobacter sakazakii, and Enterobacter cloacae complex were isolated from 5, 12, 36, 19, and 30 samples, respectively. During screening of CTX-resistant coliforms, K. pneumoniae, C. sakazakii, and E. cloacae complex were isolated from 8, 1, and 21 samples, respectively. Seven K. pneumoniae and seven E. cloacae complex isolates obtained in the screening of CTX-resistant coliforms were resistant to at least one of the three third-generation cephalosporins (CTX, ceftazidime, and cefpodoxime). Moreover, one E. cloacae complex cluster IV and all K. pneumoniae isolates were positive for extended-spectrum β-lactamase genes or plasmid-mediated AmpC β-lactamase genes or both. Additionally, two extended-spectrum β-lactamase-producing K. pneumoniae isolates and one AmpC β-lactamase-producing E. cloacae complex cluster IV isolate were positive for the plasmid-mediated quinolone resistance determinants and also had amino acid alterations in the quinolone resistance-determining regions of GyrA and ParC. Furthermore, 10 E. cloacae complex isolates were positive for the plasmid-mediated fosfomycin resistance gene fosA. As pepper is often consumed without a heating process, the possible spread to humans of foodborne, opportunistic, and nosocomial infection pathogens or resistance genes from foods prepared or seasoned with pepper cannot be excluded. Therefore, it is necessary to handle pepper by using hygienic conditions during the cultivation, harvesting and processing steps., (Copyright ©, International Association for Food Protection.)

To investigate the dissemination of ESBL/pAmpC-producing E. coli within the food distribution system of Ho Chi Minh City (HCMC), Vietnam, the prevalence of ESBL/pAmpC-producing E. coli strains in chicken meat, pork, beef, and fish/shrimp samples obtained from slaughterhouses, a wholesale market, and supermarkets was examined. Among the total of 330 collected food samples, ESBL/pAmpC-producing E. coli was detected in 150 samples (45.5%). The highest prevalence of these isolates was in chicken meat (76/82, 92.7%), followed by pork (32/92, 34.8%), beef (18/74, 34.3%), and fish/shrimp (24/82, 29.3%). A total of 342 strains of ESBL/pAmpC-producing E. coli were isolated from 150 positive food samples. The most prevalent genes responsible for ESBL or pAmpC activity belonged to the CTX-M-9 (110/342, 31.2%), CTX-M-1 (102/342, 29.8%), and CIT (118/342, 34.5%) groups. To our knowledge, this is the first report of the high occurrence of pAmpC (37.1%) in animal-based food in Vietnam. Among the 342 total ESBL/pAmpC-producing E. coli isolates, 276 (80.7%) were resistant to at least 6 antibiotic agents. Notably, high percentages of resistance to ciprofloxacin and fosfomycin were found in isolates from chicken (80.5% and 50.8%, resp.). These findings demonstrate that animal-based food products in HCMC represent a major reservoir of ESBL/pAmpC-producing E. coli.

Prolonged agonist stimulation of the μ-opioid receptor (MOR) initiates receptor regulatory events that rapidly attenuate receptor-mediated signaling (homologous desensitization). Emerging evidence suggests that persistent MOR stimulation can also reduce responsiveness of effectors to other G-protein-coupled receptors, termed heterologous desensitization. However, the mechanisms by which heterologous desensitization is triggered by MOR stimulation are unclear. This study used whole-cell patch-clamp recordings of ligand activated G-protein-activated inwardly rectifying potassium channel currents in mouse brain slices containing locus ceruleus (LC) neurons to determine the effects of prolonged stimulation of MOR on α(2)-adrenoceptor (α(2)-AR) function. The results show distinct and sequential development of homologous and heterologous desensitization during persistent stimulation of MOR in LC neurons with Met(5)-enkephalin (ME). ME stimulation of MOR promoted rapid homologous desensitization that reached a steady state after 5 min and partially recovered over 30 min. Longer stimulation of MOR (10 min) induced heterologous desensitization of α(2)-AR function that exhibited slower recovery than homologous desensitization. Heterologous (but not homologous) desensitization required β-arrestin-2 (βarr-2) because it was nearly abolished in βarr-2-knockout (ko) mice. Heterologous (but not homologous) desensitization was also prevented by inhibition of ERK1/2 and c-Src signaling in wild-type (wt) mouse LC neurons. Heterologous desensitization may be physiologically relevant during exposure to high doses of opioids because α(2)-AR-mediated slow inhibitory postsynaptic currents were depressed in wt but not βarr-2 ko LC neurons after prolonged exposure to opioids. Together, these findings demonstrate a novel mechanism by which βarr-2 can regulate postsynaptic responsiveness to neurotransmitter release.

Agonists acting on µ-opioid receptors (MOR) are very effective analgesics but cause tolerance during long-term or repeated exposure. Intensive efforts have been made to find novel opioid agonists that are efficacious analgesics but can elude the signalling events that cause tolerance. µ-Opioid agonists differentially couple to downstream signalling mechanisms. Some agonists, such as enkephalins, D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO), methadone and sufentanyl are efficacious at mediating G-protein and effector coupling, as well as triggering MOR regulatory events that include MOR phosphorylation, β-arrestin binding, receptor endocytosis and recycling. By contrast, morphine and closely related alkaloids can mediate efficacious MOR-effector coupling but poorly trigger receptor regulation. Several models have been proposed to relate differential MOR regulation by different opioids with their propensity to cause tolerance. Most are based on dogma that β-arrestin-2 (βarr-2) binding causes MOR desensitization and/or that MOR endocytosis and recycling are required for receptor resensitization. This review will examine some of these notions in light of recent evidence establishing that MOR dephosphorylation and resensitization do not require endocytosis. Recent evidence from opioid-treated animals also suggests that impaired MOR-effector coupling is driven, at least in part, by enhanced desensitization, as well as impaired resensitization that appears to be βarr-2 dependent. Better understanding of how chronic exposure to opioids alters receptor regulatory mechanisms may facilitate the development of effective analgesics that produce limited tolerance., (© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.)

Chronic morphine treatment produces behavioral and cellular opioid tolerance that has been proposed to be caused by attenuated μ-opioid receptor (MOR) recovery from desensitization (resensitization). The process of MOR resensitization is thought to require βarrestin-2 (βarr-2)-dependent trafficking of desensitized receptors to endosomal compartments, followed by recycling of resensitized receptors back to the plasma membrane. However, there is little direct evidence for this, particularly in native neurons. This study used whole-cell patch-clamp recording in locus ceruleus (LC) neurons from wild-type (w.t.) and βarr-2 knock-out (k.o.) mice to examine whether βarr-2/dynamin-dependent trafficking is required for MOR resensitization in neurons from opioid-naive and morphine-treated mice. Surprisingly, recovery of MOR from acute desensitization in LC neurons does not require βarr-2- or dynamin-dependent trafficking. To the contrary, MOR resensitization was accelerated by disruption of either βarr-2 or dynamin function. Chronic morphine treatment caused cellular MOR tolerance and concurrently impaired MOR resensitization in neurons from w.t. mice, as expected from previous studies, but neither occurred in neurons from βarr-2 k.o. mice. Moreover, the impairment of MOR resensitization caused by chronic morphine was reversed in w.t. neurons when G-protein-coupled receptor kinase-2 (GRK2) or dynamin function was disrupted. Together, these results establish that βarr-2/dynamin-dependent receptor regulation is not required for MOR resensitization in LC neurons. Furthermore, chronic morphine treatment modifies GRK2-βarr-2-dynamin-dependent MOR trafficking to impair receptor resensitization, thereby contributing to opioid tolerance in LC neurons by reducing the number of functional receptors on the surface membrane.

Objective: Because previous preclinical and clinical studies have implicated the endogenous opioid system in major depression and in the neurochemical action of antidepressants, the authors examined how DNA variation in the mu-opioid receptor gene may influence population variation in response to citalopram treatment., Method: A total of 1,953 individuals from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study were treated with citalopram and genotyped for 53 single nucleotide polymorphisms (SNPs) in a 100-kb region of the OPRM1 gene. The sample consisted of Non-Hispanic Caucasians, Hispanic Caucasians, and African Americans. Population stratification was corrected using 119 ancestry informative markers and principal components analysis. Markers were tested for association with phenotypes for general and specific citalopram response as well as remission., Results: Association between one SNP and specific citalopram response was observed. After Bonferroni correction, the strongest finding was the association between the rs540825 SNP and specific response. The rs540825 polymorphism is a nonsynonymous SNP in the final exon of the mu-opioid receptor-1X isoform of the OPRM1 gene, resulting in a histidine to glutamine change in the intracellular domain of the receptor. When Hispanic and Non-Hispanic Caucasians were analyzed separately, similar results in the population-corrected analyses were detected., Conclusions: These results suggest that rates of response to antidepressants and consequent remission from major depressive disorder are influenced by variation in the mu-opioid receptor gene as a result of either an effect on placebo response or true pharmacologic response.

Sustained stimulation of G-protein coupled receptors (GPCRs) leads to rapid loss of receptor function (acute desensitization). For many GPCRs including the mu-opioid receptor (MOR), an accepted mechanism for acute desensitization is through G-protein coupled receptor kinase (GRKs) mediated phosphorylation of the receptor, which facilitates the binding of beta-arrestins (betaarrs) to the receptor and then promotes endocytosis. However, the mechanism(s) that mediate acute desensitization have not yet been well defined in native neurons. This study used whole-cell patch clamp recording of G-protein coupled inward-rectifying potassium (GIRK) currents to assay MOR function and identify mechanisms of acute MOR desensitization in locus ceruleus (LC) neurons. The rate and extent of MOR desensitization were unaffected by beta(arr)-2 knock-out. Disruption of GRK2 function via inhibitory peptide introduced directly into neurons also failed to affect desensitization in wild type or beta(arr)-2 knock-outs. Inhibition of ERK1/2 activation alone had little effect on acute desensitization. However, when both GRK2-beta(arr)-2 and ERK1/2 functions were disrupted simultaneously, desensitization of MOR was nearly abolished. Together, these results suggest that acute desensitization of MOR in native LC neurons is determined by at least two molecular pathways, one involving GRK2 and beta(arr)2, and a parallel pathway mediated by activated ERK1/2.

Morphine has been widely accepted as the opioid agonist that sustains signaling because it does not cause receptor desensitization or internalization. This notion has led to the hypothesis that long-term morphine treatment initiates downstream adaptations that underlie tolerance and dependence. This study uses whole-cell recordings from neurons in the locus ceruleus to measure the potassium current induced by morphine. The results show that morphine does cause short-term desensitization. The desensitization induced by morphine was slower and smaller then that induced by [MET](5)-enkephalin (ME). After a brief application of a saturating concentration of ME, the current induced by morphine was smaller, and desensitization was not observed. In tissue taken from morphine-treated animals, the peak current induced by morphine was the same as in untreated animals, but morphine-induced desensitization was facilitated. The results suggest that morphine, like other agonists, can initiate receptor desensitization to decrease signaling.

Tolerance and dependence result from long-term exposure to opioids, and there is growing evidence linking acute receptor desensitization to these more long-term processes. Receptor desensitization encompasses a series of events leading to the loss of receptor function and internalization. This study examines the onset and recovery from desensitization in locus ceruleus neurons recorded in brain slices taken from animals that have been chronically treated with morphine. After chronic morphine treatment, desensitization was altered as follows. First, the rate of desensitization was increased. Second, recovery from desensitization was always incomplete, even after a brief (1-2 min) exposure to agonist. This contrasts with experiments in controls in which recovery from desensitization, after a brief exposure to agonist, was complete within 25 min. Finally, morphine-6-beta-D-glucuronide, a metabolite of morphine that was ineffective at causing desensitization in controls, induced significant desensitization in slices from morphine-treated animals. When brain slices from controls were treated with inhibitors of PKC or monensin, agents known to compromise G-protein-coupled receptor resensitization, desensitization was increased, and recovery was significantly reduced. These results indicate that receptor resensitization maintains signaling during periods of intense and sustained stimulation. After chronic morphine treatment, desensitization is potentiated, and receptor resensitization is compromised.