Pharmacological Reports最新文献

{"title":"Acute anticonvulsant effects of dapsone on PTZ- and MES-induced seizures in mice: NLRP3 inflammasome inhibition and Nrf2/HO-1 pathway preservation.","authors":"Ali Lesani, Fatemeh Mashaknejadian Behbahani, Mohammad Amin Manavi, Razieh Mohammad Jafari, Hamed Shafaroodi, Saman Khosravi, Ahmad Reza Dehpour","doi":"10.1007/s43440-025-00698-6","DOIUrl":"10.1007/s43440-025-00698-6","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy, a neurological disorder characterized by recurrent seizures, presents considerable difficulties in treatment, particularly when dealing with drug-resistant cases. Dapsone, recognized for its anti-inflammatory properties, holds promise as a potential therapeutic option. However, its effectiveness in epilepsy requires further investigation. The aim of this study is to explore the effects of dapsone on seizure activity and neuroinflammation, particularly through the nuclear factor erythroid-2-related factor (Nrf2)/ Heme Oxygenase 1 (HO-1) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) pathways, to better understand its therapeutic potential.</p><p><strong>Methods: </strong>To evaluate the effects of dapsone, two seizure models were utilized in mice: pentylenetetrazole (PTZ)-induced clonic seizures and maximal electroshock (MES)-induced generalized tonic-clonic seizures (GTCS) in mice. The impact of dapsone on neuroinflammatory markers and oxidative stress pathways, specifically Nrf2/HO-1 and NLRP3, as well as interleukin-1β (IL-1β), IL-8, and IL-18, was assessed using Western blotting and ELISA techniques.</p><p><strong>Results: </strong>In this study, dapsone (2, 5, 10, and 20 mg/kg, ip) showcased a significant increase in clonic seizure threshold following intravenous infusion of PTZ. Notably, doses of 5, 10, and 20 mg/kg exhibited increased latency and decreased the number of seizures. Additionally, dapsone at 10 and 20 mg/kg prevented the incidence of GTCS and subsequent mortality in the MES model. Furthermore, Dapsone demonstrated modulation of Nrf2/ HO-1 and NLRP3 IL-1 β/IL-18 pathways.</p><p><strong>Conclusion: </strong>This study highlights the therapeutic potential of dapsone in epilepsy, emphasizing the involvement of Nrf2/HO-1 and NLRP3 pathways. These findings provide a foundation for future clinical research aimed at developing dapsone-based therapies for drug-resistant epilepsy.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"450-462"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal amyloid model of Alzheimer's disease - potential opportunities and challenges.","authors":"Rakesh Kumar Singh","doi":"10.1007/s43440-024-00692-4","DOIUrl":"10.1007/s43440-024-00692-4","url":null,"abstract":"<p><p>Amyloid beta 1-42 (Aβ_1-42) peptide is one of the most studied disease-related amyloidogenic peptides implicated in the pathophysiology of Alzheimer's disease (AD). Despite significant scientific breakthroughs in the recent past, the existing non-transgenic animal models do not demonstrate accurate pathology of AD progression. This review has presented a concise mechanistic understanding of the intranasal amyloid-based animal model of AD, along with its advantages, challenges, and major limitations. Furthermore, discussions on how to combat these challenges to pave the road toward developing novel therapeutics for AD, have also been included. Preclinical exploration of repeated intranasal amyloid-beta exposure would certainly aid the translational development of a robust animal model of AD. This will also provide a better understanding of disease progression and pathology in the intranasal animal model.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"425-433"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical application of melatonin for pancreas disorders: protective roles against inflammation, malignancy, and dysfunctions.","authors":"Mohammad Sheibani, Azam Hosseinzadeh, Iman Fatemi, Ali Jamshidi Naeini, Saeed Mehrzadi","doi":"10.1007/s43440-024-00683-5","DOIUrl":"10.1007/s43440-024-00683-5","url":null,"abstract":"<p><p>Melatonin, a hormone primarily produced by the pineal gland, exhibits a range of physiological functions that extend beyond its well-known role in regulating circadian rhythms. This hormone influences energy metabolism, modulates insulin sensitivity, and plays a significant role in controlling sleep patterns and food intake. Notably, melatonin is also synthesized in various peripheral organs, including the gastrointestinal system and pancreas, suggesting its function as a local hormone. The presence of melatonin receptors in the pancreas underscores its relevance in pancreatic physiology. Pancreatic disorders, such as diabetes mellitus (DM), pancreatitis, and pancreatic cancer, often stem from inflammatory processes. The majority of these conditions are characterized by dysregulated immune responses and oxidative stress. Melatonin's anti-inflammatory properties are mediated through the inhibition of pro-inflammatory cytokines and the activation of antioxidant enzymes, which help to mitigate cellular damage. Furthermore, melatonin has demonstrated pro-apoptotic effects on cancer cells, promoting cell death in malignant tissues while preserving healthy cells. Thus, melatonin emerges as a multifaceted agent with significant therapeutic potential for pancreatic disorders. Its ability to reduce inflammation and oxidative stress positions it as a promising adjunct therapy for conditions such as diabetes mellitus, pancreatitis, and pancreatic cancer. By modulating immune responses and enhancing cellular resilience through antioxidant mechanisms, melatonin not only addresses the symptoms but also targets the underlying pathophysiological processes associated with these disorders. This review aims to categorize and summarize the impacts of melatonin on pancreatic functions and disorders, emphasizing its potential as a therapeutic agent for managing pancreatic dysfunctions. Future research should focus on elucidating the precise mechanisms by which melatonin exerts its protective effects on pancreatic tissues and exploring optimal dosing strategies for clinical applications. The integration of melatonin into treatment regimens may enhance existing therapies and offer new hope for individuals suffering from pancreatic dysfunctions.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"315-332"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting GABA signaling in type 1 diabetes and its complications- an update on the state of the art.","authors":"Dariusz Łaszczych, Aleksandra Czernicka, Katarzyna Łaszczych","doi":"10.1007/s43440-025-00697-7","DOIUrl":"10.1007/s43440-025-00697-7","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is an autoimmune disease that leads to the progressive destruction of insulin-producing β cells, resulting in lifelong insulin dependence and a range of severe complications. Beyond conventional glycemic control, innovative therapeutic strategies are needed to address the underlying disease mechanisms. Recent research has highlighted gamma-aminobutyric acid (GABA) as a promising therapeutic target for T1D due to its dual role in modulating both β cell survival and immune response within pancreatic islets. GABA signaling supports β cell regeneration, inhibits α cell hyperactivity, and promotes α-to-β cell transdifferentiation, contributing to improved islet function. Moreover, GABA's influence extends to mitigating T1D complications, including nephropathy, neuropathy, and retinopathy, as well as regulating central nervous system pathways involved in glucose metabolism. This review consolidates the latest advances in GABA-related T1D therapies, covering animal preclinical and human clinical studies and examining the therapeutic potential of GABA receptor modulation, combination therapies, and dietary interventions. Emphasis is placed on the translational potential of GABA-based approaches to enhance β cell viability and counteract autoimmune processes in T1D. Our findings underscore the therapeutic promise of GABA signaling modulation as a novel approach for T1D treatment and encourage further investigation into this pathway's role in comprehensive diabetes management.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"409-424"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Red cell microparticles produced using high-pressure extrusion enhance both primary and secondary hemostasis.","authors":"Snigdha Sama, Sunjoo Cho, Ashish K Rehni, Wenche Jy, Kunjan R Dave","doi":"10.1007/s43440-024-00688-0","DOIUrl":"10.1007/s43440-024-00688-0","url":null,"abstract":"<p><strong>Background: </strong>Current therapies to treat excessive bleeding are associated with significant complications, which may outweigh their benefits. Red blood cell-derived microparticles (RMPs) are a promising hemostatic agent. Previous studies demonstrated that they reduce bleeding in animal models, correct coagulation defects in patient blood, and have an excellent safety profile. However, their exact mechanism of action is not known. We investigated the potential role of RMPs on primary and secondary hemostasis.</p><p><strong>Methods: </strong>To evaluate the effects of RMPs, prepared using high-pressure extrusion, on primary hemostasis, we employed platelet aggregometry with platelet inhibitors, eptifibatide, and ticagrelor, with and without RMPs. To evaluate their effects on secondary hemostasis, we employed thromboelastography with plasma deficient in factors VII, VIII, IX, XI, and XII with and without RMPs.</p><p><strong>Results: </strong>We found that RMPs significantly increased collagen-induced platelet aggregation. However, there were no significant differences with and without RMP in the presence of the platelet inhibitors, indicating that RMPs may work through these receptors, either directly or indirectly. For secondary hemostasis, RMPs significantly decreased clotting times for plasma deficient in factors VII, VIII, IX, and XI but not in XII.</p><p><strong>Conclusions: </strong>Our results indicate that RMPs enhance primary hemostasis and both pathways of secondary hemostasis.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"508-516"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Olaparib-induced hyperglycemia in ovarian cancer patients - a case series analysis of a three-month therapy with a consideration of BMI.","authors":"Joanna Stanisławiak-Rudowicz, Edyta Szałek, Barbara Więckowska, Edmund Grześkowiak, Radosław Mądry","doi":"10.1007/s43440-025-00702-z","DOIUrl":"10.1007/s43440-025-00702-z","url":null,"abstract":"<p><strong>Background: </strong>Olaparib is a relatively new poly(ADP-ribose) polymerase inhibitor (PARPi) administered to ovarian cancer (OC) patients with a complete or partial response to first-line chemotherapy. One of the metabolic side effects of olaparib is the disruption of glucose homeostasis, often resulting in hyperglycemia The study was a retrospective analysis of olaparib-induced hyperglycemia in OC patients with initial normoglycemia following the first, second, and third month of olaparib treatment METHODS: The study involved 32 OC patients, classified into three groups according to their Body Mass Index (BMI): normal BMI (BMI 18.5-24.9 kg/m²; n = 13), overweight (BMI 25-29.9 kg/m²; n = 13), and obese (BMI ≥ 30 kg/m²; n = 6). The fasting glucose (FG) concentration was evaluated after the first, second, and third cycle of olaparib treatment (a cycle is the equivalent of 28 days of treatment). The severity of the observed hyperglycemia was assessed using the Common Terminology Criteria for Adverse Events (CTCAE v5.0).</p><p><strong>Results: </strong>A significant increase in glycemia was observed after the first and second cycles of olaparib treatment in the group with normal BMI and after the third cycle in overweight and obese patients. There were no significant differences in glucose levels among the groups following the first, the second, and the third cycle. Grade 1 hyperglycemia with impaired fasting glucose levels (5.6-6.9 mmol/l) was found in 15 patients (normal BMI: n = 4, overweight: n = 9, and obesity: n = 2), while glycemia typical of diabetes (≥ 7.0 mmol/l) was observed in one obese patient.</p><p><strong>Conclusions: </strong>Regardless of the weight of OC patients, it is essential to control glycemia during olaparib treatment.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"500-507"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Access to high-fat diet results in increased sensitivity to the psychostimulant effects of MDPV in mice.","authors":"Jakub Wojcieszak, Katarzyna Kuczyńska, Adrianna Leszczyńska, Eryk Naraziński, Maria Cichalewska-Studzińska","doi":"10.1007/s43440-025-00701-0","DOIUrl":"10.1007/s43440-025-00701-0","url":null,"abstract":"<p><strong>Background: </strong>The current study investigated the effects of high-fat diet on acute response to 3,4-methylenedioxypyrovalerone (MDPV) in mice. MDPV is a beta-cathinone derivative endowed with psychostimulant activity. Similarly to recreational substances, consumption of palatable food stimulates the mesolimbic dopaminergic system, resulting in neuroadaptive changes.</p><p><strong>Methods: </strong>Adolescent C57BL/6N mice were fed either control diet (CD), 10% of kcal from fat, or high-fat diet (HFD), 60% of kcal from fat. After eight weeks, one group of HFD-fed mice had their diet changed to CD for an additional two weeks. Fasting glucose levels and glucose tolerance were measured to detect impairment in glucose metabolism. Subsequently, the mice were treated with either MDPV (1 mg/kg) or saline, and their locomotor activity was measured. Using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), the expression of dopamine receptor D1 (Drd1), dopamine receptor D2 (Drd2), and FBJ osteosarcoma oncogene B (FosB) genes was measured in the striatum of mice.</p><p><strong>Results: </strong>Feeding with HFD caused obesity and glucose intolerance in mice. Restriction of fat reduced body mass and reversed impairment of glucose metabolism. HFD-fed mice responded to MDPV with higher potency than CD-fed counterparts, with an increased incidence of stereotypies. A change of diet partially reversed this effect. Downregulation of Drd2 was observed in the mice that switched from HFD to CD, whereas treatment with MDPV caused upregulation of FosB only in the CD-fed mice.</p><p><strong>Conclusions: </strong>Current results suggest that obesity may increase sensitivity to psychostimulant effects of MDPV and elevate the risk of addiction as mice fed with HFD responded to acute treatment with MDPV with higher potency and showed tolerance of FosB induction in response to the drug.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"434-449"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paracetamol, its metabolites, and their transfer between maternal circulation and fetal brain in mono- and combination therapies.","authors":"Yifan Huang, Fiona Qiu, Katarzyna M Dziegielewska, Mark D Habgood, Norman R Saunders","doi":"10.1007/s43440-024-00682-6","DOIUrl":"10.1007/s43440-024-00682-6","url":null,"abstract":"<p><strong>Background: </strong>Due to its availability and perceived safety, paracetamol is recommended even during pregnancy and for neonates. It is used frequently alone or in combination with other drugs required for the treatment of various chronic conditions. The aim of this study was to investigate potential effects of drug interactions on paracetamol metabolism and its placental transfer and entry into the developing brain.</p><p><strong>Methods: </strong>Sprague Dawley rats at postnatal day P4, pregnant embryonic day E19 dams, and non-pregnant adult females were administered paracetamol (15 mg/kg) either as monotherapy or in combination with one of seven other drugs: cimetidine, digoxin, fluvoxamine, lamotrigine, lithium, olanzapine, valproate. Concentrations of parent paracetamol and its metabolites (paracetamol-glucuronide, paracetamol-glutathione, and paracetamol-sulfate) in plasma, cerebrospinal fluid (CSF) and brain were measured by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and their entry into the brain, CSF and transfer across the placenta were estimated.</p><p><strong>Results: </strong>In monotherapy, concentration of parent paracetamol in plasma, CSF, and brain remained similar and at all ages brain entry was unrestricted. In combination therapies, CSF entry of paracetamol increased following co-treatment with olanzapine. Placental transfer of parent paracetamol remained unchanged, however, transfer of paracetamol-sulfate increased with lamotrigine co-administration. Acutely administered paracetamol was more extensively metabolized in adults compared to younger ages resulting in increased concentration of its metabolites with age.</p><p><strong>Conclusions: </strong>Developmental changes in the apparent brain and CSF entry of paracetamol appear to be determined more by its metabolism, rather than by cellular control of its transfer across brain and placental barriers.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"474-489"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Off-label use of anlotinib in malignancies' treatment: efficacy and management of adverse reactions.","authors":"Guangli Wang, Yuling Wang, Changhao Jin, Xiaodan Sun","doi":"10.1007/s43440-025-00700-1","DOIUrl":"10.1007/s43440-025-00700-1","url":null,"abstract":"<p><p>Anlotinib is a novel small-molecule multi-target tyrosine kinase inhibitor (TKIs) independently developed in China, it possesses the functions of inhibiting tumor angiogenesis and suppressing tumor growth. Anlotinib has achieved notable therapeutic effects in approved indications for advanced non-small cell lung cancer, soft tissue sarcoma, small cell lung cancer, and medullary thyroid carcinoma. Additionally, with unanimous expert consensus, it has been used off-label in various other tumors, yielding favorable outcomes. This article reviews the efficacy and common adverse reactions, as well as their management, of off-label use of anlotinib in various malignant tumors.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"392-408"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[¹¹C]MK-6884 PET imaging reveals lower M₄ muscarinic acetylcholine receptor availability following cocaine self-administration in male rats.","authors":"Krishna K Gollapelli, Ivan Krizan, Bhuvanachandra Bhoopal, Naresh Damuka, Carson Moriarty, Mack Miller, Kiran K Solingapuram Sai, Robert W Gould","doi":"10.1007/s43440-025-00695-9","DOIUrl":"10.1007/s43440-025-00695-9","url":null,"abstract":"<p><strong>Background: </strong>Cocaine Use Disorder (CUD) remains a significant problem in the United States, with high rates of relapse and no present FDA-approved treatment. The acetylcholine neurotransmitter system, specifically through modulation of muscarinic acetylcholine receptor (mAChR) function, has shown promise as a therapeutic target for multiple aspects of CUD. Enhancement of the M₄ mAChR subtype via positive allosteric modulation has been shown to inhibit the behavioral and neurochemical effects of cocaine across several rodent models of CUD. However, it is unclear how cocaine exposure affects M₄ mAChR expression or distribution.</p><p><strong>Objectives: </strong>To evaluate the effects of cocaine self-administration on M₄ mAChR availability using [¹¹C]MK-6884 in vivo PET imaging in rats that self-administered cocaine (cocaine SA) or sucrose pellets (control).</p><p><strong>Methods: </strong>Sprague-Dawley rats self-administered cocaine or sucrose pellets for 15 days under 2-h or 4-h sessions followed by PET imaging with [¹¹C]MK-6884, a radiolabeled M₄ selective positive allosteric modulator to determine the effects of cocaine on [¹¹C]MK-6884 standard uptake values with cerebellum as reference (SUVr).</p><p><strong>Results: </strong>Cumulative cocaine intake ranged between 324 and 776 mg/kg. Cocaine self-administration was associated with significantly lower [¹¹C]MK-6884 SUVrs in the cortex, hippocampus, and striatum compared to cocaine-naive rats, with a negative correlation between radiotracer SUVrs and cocaine intake in the hippocampus.</p><p><strong>Conclusions: </strong>These results suggest that cocaine self-administration decreases M₄ mAChR availability, providing further support for pursuing activation/enhancement of M₄ mAChR function as a viable pharmacotherapeutic approach for CUD.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"532-541"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}