Pharmacological Research - Reports最新文献

{"title":"Veterinary bacteriostatic and ionophore antibiotics in aquatic organisms: A systematic review and scientometric analysis of biomarker and exposure concentrations","authors":"Thaís Pereira Nascimento ,&nbsp;Andrea Carina Crupkin ,&nbsp;Mirta Luján Menone","doi":"10.1016/j.prerep.2025.100065","DOIUrl":"10.1016/j.prerep.2025.100065","url":null,"abstract":"<div><div>The intensive use of veterinary antibiotics, particularly bacteriostatic agents and ionophores, represents an increasing ecotoxicological concern for aquatic ecosystems. This study integrates scientometric analysis with a systematic literature review specifically aimed at identifying gaps in experimental research addressing the effects of these pharmaceuticals on aquatic organisms through biomarker-based assessments. A total of 648 publications published between 1968 and 2024 were screened; however, only 20 in vivo studies involving 10 aquatic species (7 vertebrates and 3 invertebrates) met the inclusion criteria, of which 17 investigated bacteriostatic antibiotics and 3 ionophores. Acute exposure designs predominated (35 %), followed by subchronic (30 %), chronic (15 %), and combined acute–chronic (20 %) assays. Reported environmental concentrations ranged from nanograms to hundreds of micrograms per liter, whereas experimental exposures frequently reached milligram-per-liter levels — in some cases exceeding environmental concentrations by several orders of magnitude. Observed effects included oxidative stress, immunological alterations, reproductive impairment, embryotoxicity, and histopathological damage. The findings demonstrate a disproportionate reliance on standard model organisms, particularly <em>Danio rerio</em>, and a notable scarcity of studies involving native or ecologically relevant species. This review highlights a critical need for future research to adopt chronic exposure scenarios, incorporate native species, environmentally relevant concentrations, and apply standardized- sensitive biomarkers. Addressing these gaps is essential to advance the environmental risk assessment of veterinary antibiotics and to support more effective and evidence-based environmental policymaking.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100065"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin alleviates streptozotocin-induced neuropathic pain in rat model: Involvement of noradrenergic receptor pathways","authors":"Ilhem Dallali ,&nbsp;Ahmed Hasan ,&nbsp;Feyza Alyu Altınok ,&nbsp;Nurcan Bektas Turkmen ,&nbsp;Yusuf Ozturk","doi":"10.1016/j.prerep.2025.100068","DOIUrl":"10.1016/j.prerep.2025.100068","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic neuropathic pain is a persistent and debilitating complication of diabetes with limited treatments. Melatonin shows promise in pain modulation, though its underlying antinociceptive mechanisms remain unclear. This study investigated the analgesic efficacy of melatonin in alleviating streptozotocin-induced neuropathic pain in rats and explored the involvement of noradrenergic pathways.</div></div><div><h3>Methods</h3><div>Neuropathic pain was induced in male Sprague-Dawley rats via a single intravenous injection of streptozotocin (50 mg/kg). Melatonin (50 mg/kg, <em>i.p.</em>) was administered daily for two weeks. Gabapentin (50 mg/kg, <em>i.p.</em>) served as a positive control. Mechanical allodynia and thermal hyperalgesia were assessed using the e-Von Frey and Hargreaves tests, respectively, while locomotor activity was evaluated using an activity cage. To evaluate metabolic effects, blood glucose levels were monitored throughout the study. Adrenergic antagonists’ prazosin (α1, 10 mg/kg), yohimbine (α2, 4 mg/kg), and propranolol (β, 5 mg/kg) were administered prior to the final melatonin dose to assess noradrenergic involvement.</div></div><div><h3>Results</h3><div>Streptozotocin-induced diabetic rats exhibited pronounced mechanical and thermal hypersensitivity. Subacute melatonin treatment significantly reduced nociceptive responses and improved locomotor activity, showing efficacy comparable to gabapentin. It did not alter blood glucose levels, indicating a neutral metabolic effect. The analgesic effects of melatonin were attenuated by adrenergic antagonists, implicating noradrenergic signaling in its mechanism of action.</div></div><div><h3>Conclusions</h3><div>Melatonin exerts significant antiallodynic and antihyperalgesic effects in diabetic neuropathic rats, likely mediated via noradrenergic receptor pathways. Its neutral impact on glycemic control, combined with potential mood-regulating properties, supports its promise as a therapeutic candidate for managing diabetic neuropathic pain, pending clinical validation.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-nucleotide polymorphisms in CYP27B1 and VDR genes associated with treatment outcomes in hepatitis B and C: A minireview","authors":"Alessandra Ramalho Correia ,&nbsp;Victor Cavicchioli ,&nbsp;Lara Cândida de Sousa Machado ,&nbsp;Rahisa Scussel ,&nbsp;Ricardo Andrez Machado-de-Ávila ,&nbsp;Iane de Oliveira Pires Porto ,&nbsp;Iara Barreto Neves Oliveira","doi":"10.1016/j.prerep.2025.100061","DOIUrl":"10.1016/j.prerep.2025.100061","url":null,"abstract":"<div><div>Vitamin D, essential for immune modulation, is metabolized by enzymes encoded by the <em>CYP27B1</em> gene and exerts its effects through the vitamin D receptor (VDR). Genetic variations in these genes may influence antiviral response, particularly to treatments with pegylated interferon and ribavirin. This work consists of a descriptive literature review analyzing the influence of single-nucleotide polymorphisms (SNPs) in the <em>CYP27B1</em> and <em>VDR</em> genes on the antiviral treatment response for HBV and HCV. The results indicate that specific SNPs, such as rs4646536 and rs10877012 in the <em>CYP27B1</em> gene and rs7975232/<em>Apa</em>I, rs1544410/<em>Bsm</em>I, rs731236/<em>Taq</em>I, and rs10735810—rs2228570/<em>Fok</em>I in the <em>VDR</em> gene, may be associated with variable therapeutic responses, including higher rates of sustained virological response (SVR) and reduced viral load. Given the limited efficacy of current antiviral therapies, identifying relevant SNPs in genes related to the vitamin D pathway may help select responsive patients, personalize hepatitis B and C therapy approaches, and minimize side effects.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100061"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of cholecystokinin 2 receptor (CCK2R) in rectal cancer: Clinical relevance and in vitro targeting with a fluorescent CCK2R-binding peptide","authors":"Somayeh Rezaei ,&nbsp;Xi Zhang ,&nbsp;Ronald L.P. van Vlierberghe ,&nbsp;Amber Piet ,&nbsp;Elma Meershoek-Klein Kranenbarg ,&nbsp;Ajinkya Manelkar ,&nbsp;Yann Seimbille ,&nbsp;Peter Laverman ,&nbsp;Louise van der Weerd ,&nbsp;Alexander L. Vahrmeijer ,&nbsp;Peter J.K. Kuppen","doi":"10.1016/j.prerep.2025.100054","DOIUrl":"10.1016/j.prerep.2025.100054","url":null,"abstract":"<div><div>The cholecystokinin type 2 receptor (CCK2R), which mediates the effects of gastrin and cholecystokinin (CCK), is known to promote colorectal cancer (CRC) proliferation in advanced stages. Though well-studied in gastric and pancreatic cancers, the role of CCK2R in colorectal, especially rectal cancer (RC), is still emerging. In this research, we initially evaluated CCK2R expression across rectal and colorectal cancer cell lines using qRT-PCR to establish baseline expression patterns. To explore the potential for near-infrared (NIR) fluorescence-based tumor targeting, we synthesized a CCK2R-binding peptide conjugate, Cy5@PP-F11, and demonstrated its receptor-specific uptake in vitro through live-cell imaging microscopy. While these results suggest promise for tumor targeting, further studies are needed to assess its <em>in vivo</em> performance and utility in fluorescence-guided surgery. In addition, a cohort of 495 Stage I-IV rectal cancer patients was analyzed using tissue microarrays (TMAs) and immunohistochemistry (IHC) to assess CCK2R expression in both tumor and normal tissues. Expression patterns and their prognostic significance were evaluated in relation to clinicopathological parameters. CCK2R localization and expression levels were quantified in both the epithelial and stromal tumor compartments, with cytoplasmic and nuclear staining specifically analyzed in the epithelial compartment. Scoring data were assessed to determine their clinical relevance. Our findings revealed significant overexpression of CCK2R in both epithelial and stromal compartments of rectal cancer tissues compared to normal tissues, showing its high suitability as target for tumor imaging. While epithelial CCK2R expression showed no significant link to clinical staging, stromal expression was notably involved, indicating a role in tumor-stroma interactions and the tumor microenvironment.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100054"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144686657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theories of drug action, 100 years of progress: From occupation to biased signaling contributions","authors":"M. Verónica Donoso,&nbsp;Isidora Rubilar,&nbsp;J. Pablo Huidobro-Toro","doi":"10.1016/j.prerep.2025.100062","DOIUrl":"10.1016/j.prerep.2025.100062","url":null,"abstract":"<div><div>A.J. Clark applied the law of mass action to explain how drugs work, a formulation known as the occupation theory. This hypothesis advanced that drugs occupy receptors through the formation of a [drug-receptor] complex intimately linked to the generation of a pharmacologic response. Full agonists were distinguished from antagonists based on the nature of the complex formed and concentration-response curves. Stephenson introduced the notion of drug efficacy and intrinsic activity to modify Clark’s proposal, explaining why antagonists, which occupy receptors, do not elicit a direct receptor-mediated response. According to this modification, partial agonists do not achieve full efficacy due to low intrinsic activity based on dose-response curves, while antagonists dramatically lack all intrinsic activity. Detailed structural biology findings of GPCRs provided new insights into possible conformational changes through the multiple forms of [drug-receptor] complexes, which ultimately cause clinical responses. Moreover, the recognition that several β-arrestins produce GPCRs' intracellular signaling through the activation of various protein kinases accounts for the novel idea that drugs that interact preferentially through this intracellular pathway, such as receptor antagonists, also elicit cellular responses. The evolution of these ideas proposed that drugs interact with the multiple receptor conformations, eliciting interactions that consequently elicits varying states of receptor activity, followed by ensuing intracellular responses. This new proposal changed the nomenclature from full agonists to selective G protein ligands and antagonists as preferential β-arrestins ligands. Agonists and antagonists are all now referred to as receptor ligands, independent of the nature of the [drug-receptor] complex formed.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100062"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetaminophen and acetaminophen-opioid combination prescribing trends among hospitalized children, adolescents, and young adults with cancer","authors":"Cheryl L. Mathis ,&nbsp;Huong D. Meeks ,&nbsp;Kevin M. Watt ,&nbsp;Luke D. Maese ,&nbsp;Jonathan E. Constance","doi":"10.1016/j.prerep.2025.100047","DOIUrl":"10.1016/j.prerep.2025.100047","url":null,"abstract":"<div><div>Acetaminophen (<strong>APAP</strong>) is a ubiquitous antipyretic and analgesic used in children in the United States (<strong>US</strong>), including those with cancer. The effects of US Food &amp; Drug Administration (<strong>FDA</strong>) guidance on APAP prescribing have been described for healthy adults and children; however, APAP use patterns in neonates, infants, children, adolescents, and young adults (<strong>CAYA</strong>) with cancer are unknown. Considering their increased risk of liver injury, APAP’s potential for causing hepatoxicity, and FDA guidance changes, this study examined the recent evolution of APAP use in CAYA with cancer. This retrospective, multi-center analysis extracted APAP prescribing data from the Pediatric Health Information System® (<strong>PHIS</strong>). Eligible patients were aged 0–26 years, had a cancer diagnosis per International Classification of Diseases (<strong>ICD</strong>) codes, and were prescribed a chemotherapeutic. APAP and APAP-opioid combination prescribing were assessed at hospital, regional, and national levels. APAP and APAP-opioid combination use changes were assessed using the non-parametric Mann-Kendall test. PHIS records for the complete years of 2004–2021 yielded 388,364 inpatient encounters for 50,779 unique patients. Of these, 87.3 % of patients received APAP. Although APAP-opioid combination use was infrequent overall, CAYA receiving APAP were more likely to receive APAP-opioid combination medications (N = 25,880, 13.4 %, p &lt; 0.001) compared to those not receiving APAP. Among specialty children’s hospitals, national APAP use was stable over the study period. Regionally, APAP use increased among Northeastern hospitals. APAP-opioid combination use decreased nationally with regional variation. In contrast to the steady decline in other regions, Southern APAP-opioid combination use was consistently elevated before declining in 2014.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100047"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supplemental use of melatonin to protect against oxidative stress induced by intensive athletic training and competition","authors":"Yupeng Cui ,&nbsp;Xiaoyan Liu ,&nbsp;Russel J. Reiter","doi":"10.1016/j.prerep.2025.100069","DOIUrl":"10.1016/j.prerep.2025.100069","url":null,"abstract":"<div><div>Ample experimental evidence supports the protective effect of melatonin against oxidative damage and fatigue induced by overload athletic training. This article aims to review recent research on the protective effect and mechanisms of melatonin against oxidative stress induced by intensive training and competition, and to provide theoretical support for its application and future research directions. The mechanism of melatonin action involves around direct scavenger of reactive oxygen species, aggregation in mitochondria, and activating signal pathways by binding to receptors. Mitochondria may be one of the most important targets of melatonin in preventing oxidative stress, histiocytic damage and metabolic disorders induced by intensive training. Given the important role of redox signaling agents in activating different signal transduction systems to elicit adaptive changes to exercise stimuli, a phased short-term mode of melatonin supplementation tailored to athletes’ redox status and training load is recommended.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100069"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145473845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring therapeutic potential of Carissa carandas for Typhoid: An integrated approach using molecular docking, MD simulation, MMGBSA, and ADMET analysis","authors":"Vanshika Chaudhary ,&nbsp;Indu Sharma ,&nbsp;Jayant Jagtap ,&nbsp;Mayank Bhushan","doi":"10.1016/j.prerep.2025.100057","DOIUrl":"10.1016/j.prerep.2025.100057","url":null,"abstract":"<div><div>Typhoid fever, caused by <em>Salmonella typhi</em>, continues to pose a significant global health challenge, particularly with the increasing prevalence of multidrug-resistant strains. Despite ongoing vaccination efforts, typhoid fever still accounts for over 9 million infections and more than 110,000 deaths annually, predominantly affecting low- and middle-income countries. This persistent burden, coupled with the rise of antibiotic resistance, underscores an urgent need for alternative therapeutic strategies. In response, this study investigates the therapeutic potential of phytochemicals derived from <em>Carissa carandas,</em> a novel and underexplored medicinal plant traditionally used in ethnomedicine, through an integrated computational approach. A comprehensive library of 143 phytochemicals was assembled and rigorously screened using Lipinski’s rule of five and ADMET parameters, which led to the identification of 42 promising candidates for further evaluation. Molecular docking studies revealed that key compounds including Ursolic acid, carissic acid, and 3-hydroxyurs-12-en-28-oic acid exhibited binding affinities of approximately –9.6, –9.4, and –9.6 kcal/mol, respectively, significantly outperforming ciprofloxacin, which showed a binding affinity of –7.0 kcal/mol. To further assess the stability of these interactions, molecular dynamics simulations were conducted over a 100 ns period. The results demonstrated outstanding structural stability of the Ursolic acid–OmpF complex, as evidenced by a strong network of hydrogen bonds throughout the simulation and minimal root-mean-square deviation (RMSD) fluctuations. Because Ursolic acid strongly interacts with the target protein, complementary MMGBSA analysis produced a total binding energy of –32.35 ± 2.87 kcal/mol. Furthermore, ADMET profiling confirmed that the lead compounds possess certain favorable pharmacokinetic properties and safety profiles and have improved drug-likeness scores relative to ciprofloxacin. These numerical outcomes suggest that C. carandas-derived compounds represent a promising phytotherapeutic approach for managing typhoid fever; therefore, further tests using both in vitro and in vivo setups are necessary to confirm this.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100057"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiproliferative effects of phytocompounds from Ichnocarpus frutescens (L.) W.T. Aiton against breast cancer cell line MDA MB-231 by in vitro and in silico analysis","authors":"Roshna Kattilaparambil ,&nbsp;Vinoth Sathasivam ,&nbsp;Saradhadevi Muthukrishnan ,&nbsp;Hemamalini Vedagiri ,&nbsp;Ashok Iyaswamy ,&nbsp;Arun Muthukrishnan ,&nbsp;Alagupandi Raman ,&nbsp;Gayathiri Gunasangkaran ,&nbsp;Janaranjani Murugesan ,&nbsp;Gurusaravanan Packiaraj","doi":"10.1016/j.prerep.2025.100058","DOIUrl":"10.1016/j.prerep.2025.100058","url":null,"abstract":"<div><div>Breast cancer is an invasive disease in women and could be a major concern due to its serious health risk. This study explores the bioactive compounds from <em>Ichnocarpus frutescens</em> root extract against breast cancer cell (MDA MB-231). The bioactive compounds from the root were extracted using various solvents. The total phenol, flavonoids, alkaloid and tannin quantified and <em>in vitro</em> antioxidant activity were also evaluated using standard methods. GCMS analysis and the binding affinity of the active components were investigated against EGFR, CHD 1, HER-2 and BRCA 1protein. The most promising active ligand was subjected to 100 ns molecular dynamics (MD) simulations. Further, cell proliferation was examined in MDA MB-231 by MTT, wound healing and staining assays. The <em>I. frutescens</em> root extract exhibited high levels secondary metabolites. Additionally, ethyl acetate (EA) extract shows highest antioxidant activity with lowest IC₅₀ values in DPPH (55.22 μg/mL) and ABTS (36.31 μg/mL) radical scavenging assay. The fourteen bioactive compounds were identified by GCMS analysis. However, it has been the first report the compound Estra-1,3,5(10)-trien-6-one, 3,17-bis(acetyloxy), 6-(O-methyloxime), (17.beta.)- exhibiting high binding affinity (-9.5) against HER-2 receptor protein. The results of the molecular dynamics indicate that the ligand forms a stronger complex with the breast cancer protein BRCA1. Furthermore, MTT assay demonstrated a significant anti-proliferative effect against MDA MB-231 breast cancer cells with IC₅₀ value of 84 μg mL⁻¹. Nuclear damage in these cells was examined using AO/EtBr and DAPI staining. <em>In vitro</em> studies confirmed the anti-proliferative activity of the extract against MDA MB-231 breast cancer cells. These findings suggest that this plant extract could be a promising source for the development of novel anti-cancer agents.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100058"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-administration of modafinil, atomoxetine, and citalopram increases exploratory behavior, produces withdrawal signs, and enhances self-administration of this drug mixture","authors":"Jorge Juárez,&nbsp;Amanda C. Hernandez De la Torre,&nbsp;Jesús E. Yepez","doi":"10.1016/j.prerep.2025.100060","DOIUrl":"10.1016/j.prerep.2025.100060","url":null,"abstract":"<div><div>The monoaminergic systems are necessary for the motor and reinforcing effects of addictive psychostimulants such as cocaine and amphetamines. The participation of the dopaminergic system (DA) in relation to these properties has been studied extensively, but the role of the noradrenergic (NA) and serotoninergic (5-HT) systems has not been clarified. Clinical psychostimulants like modafinil have not shown clear evidence of addictive effects, perhaps due to differential activity in the latter two systems. The aim of this study was to determine the effect of monotherapies with modafinil (MOD, a drug with main activity in the inhibition of dopamine reuptake), atomoxetine (ATX, a selective norepinephrine reuptake inhibitor), and citalopram (CIT, a selective serotonin reuptake inhibitor), and coadministration (MOD+ATX+CIT), on locomotor activity, signs of anhedonia after drug withdrawal and self-administration of MOD and the mixture of these substances. Male Wistar rats were treated chronically (16 days) via the endogastric route with ATX at 2 mg/kg, CIT at 3 mg/kg, MOD at 60 mg/kg, or a combination (2ATX+3CIT+60MOD). The co-administered rats (COAD) increased exploratory behavior and showed signs of anhedonia post-withdrawal. The MOD and COAD groups showed higher MOD intake after being water-deprived for 12 h, while a sensitization of exploratory behavior was observed in the COAD group after consuming the ATX+CIT+MOD mixture. Higher seeking self-administration of the mixture was noted only in the COAD group. Results suggest that early simultaneous activation of the DA, NA, and 5-HT systems produces plastic changes that favor the posterior self-administration and rewarding effects of drugs that activate these three neurotransmission systems.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100060"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144841797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}