Research Results in Pharmacology最新文献

{"title":"Effects of kappa-opioid agonist U-50488 and p38 MAPK inhibitor SB203580 on the spike activity of pyramidal neurons in the basolateral amygdala","authors":"K. Kalitin, A. Spasov, O. Mukha","doi":"10.18413/rrpharmacology.10.400","DOIUrl":"https://doi.org/10.18413/rrpharmacology.10.400","url":null,"abstract":"Introduction: Kappa-opioid receptor (KOR) signaling in the basolateral amygdala (BLA) underlies KOR agonist-induced aversion. In this study, we aimed to understand the individual and combined effects of KOR agonist U-50488 and p38 MAPK inhibitor SB203580 on the spiking activity of pyramidal neurons in the BLA to shed light on the complex interplay between KORs, the p38 MAPK, and neuronal excitability.\u0000Materials and Methods: Electrophysiological experiments were performed using the patch-clamp technique in the whole-cell configuration. Rat brain slices containing the amygdala were prepared, and pyramidal neurons within the BLA were visually patched and recorded in the current clamp mode. The neurons were identified by their accommodation properties and neural activity signals were amplified and analyzed. Using local perfusion, we obtained three dose-response curves for: (a) U-50488 (0.001–10 μM); (b) U-50488 (0.001–10 μM) in the presence of SB203580 (1 μM); and (c) U-50488 (0.01–10 μM) in the presence of SB203580 (5 μM).\u0000Results: After the application of U-50488, pyramidal neurons had a higher action potential firing rate in response to a current injection than control neurons (p<0.001). The dose-dependent curves we obtained indicate that the combination of U-50488 and SB203580 results in non-competitive antagonism. This conclusion is supported by the observed change in the curve’s slope with reduction in the maximum effect of U-50488. Thus, it can be assumed that the increase in spike activity of pyramidal neurons of the amygdala is mediated through the beta-arrestin pathway. When this pathway is blocked, the spike activity reverts to its baseline level.\u0000Conclusion: Our study found that the KOR agonist-induced spiking activity of the BLA pyramidal neurons is mediated by the beta-arrestin pathway and can be suppressed by the application of the p38 MAPK inhibitor SB203580.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140487495","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":"Spontaneous remyelination following dimethyl sulfoxide-induced demyelination is accompanied by behavioral and neurological alteration in mice","authors":"N. V. Kudryashov, A. A. Gorbunov, N. B. Sviridkina, S. E. Mironov, D. A. Tikhonov, A. A. Nedorubov, V. P. Fisenko","doi":"10.18413/rrpharmacology.9.10059","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10059","url":null,"abstract":"Introduction: Dimethyl sulfoxide (DMSO) is a commonly used solvent that can be applied in experimental studies for preparation of hydrophobic solutions as well as in capacity of a cryopreservative in transplantology. According to modern data acquired from in vitro experiments, DMSO is able to change the structure of myelin by decreasing synthesis of its main components and inhibiting oligodendrocyte genesis. Aim of the study: We studied influence of DMSO on anxiety and compulsive-like behavior, pain perception, motor coordination and myelin quantity in the corpus callosum of the C57BL/6 mice brain after prolonged oral administration of the solvent and 4 weeks after administration was stopped. Materials and Methods: All the experiments were conducted on male inbreed C57BL/6 mice. DMSO was added to drinking water to achieve 0.01% concentration, and the obtained solution was administered ad libitum for 6 weeks. After 6 weeks of administration of DMSO and 4 weeks after administration of DMSO was stopped, anxiety-like behavior in open field test, compulsive-like behavior in marble burying test, motor coordination in rotarod test, pain perception in tail-immersion test, as well as myelin quantity in the corpus callosum were evaluated. Results: It was established that DMSO consumed for 6 weeks was associated with decrease in the myelin quantity in thecorpus callosum and thermal hyperalgesia in tail-immersion test. During 4-week period after DMSO administration was stopped, attenuation of demyelination was observed, followed by an increase in thermal hyperalgesia in tail-immersion test, as well as vertical locomotion and exploratory activity in open field test. Conclusions: 6-week ad libitum administration of 0.01% DMSO solution was associated with demyelination in corpus callosum of С57BL/6 mice, followed by thermal hyperalgesia. Cessation of DMSO led to spontaneous remyelination with an increase in thermal hyperalgesia, vertical locomotion and exploratory activity of mice.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139131592","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":"Screening of anti-inflammatory activity of 4.5-dihydroisoxazol-5-carboxamide (PAR-2 inhibitors) based on formaldehyde oedema model among white lab rats","authors":"Mikhail K. Korsakov, Vladimir N. Fedorov, Nikolay A. Smirnov, A. Shetnev, Olga V. Leonova, Nikita N. Volkhin, Aleksandr I. Andreyev","doi":"10.18413/rrpharmacology.9.10061","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10061","url":null,"abstract":"Introduction: Rheumatoid arthritis (RА) is an immune-inflammatory disease intrinsic to up to 1.0% of the world’s population. Standard drugs for RA therapy are basic medications, glucocorticoids and non-steroid anti-inflammatory drugs, which often only ease or hinder the course of disease, not curing the patient completely. Also, on the average 20-50 % of patients are unresponsive to treatment, allergic to the prescribed drugs or find them ineffective. That is why medications with a different mechanism of action are being widely researched, some of them being antagonists of proteinase-activated receptors (PAR-2). Materials and Methods: The inflammatory process was reproduced by injecting a 2% solution of neutral formalin in a volume of 0.1 mL under the aponeurosis of the posterior left foot. A total of 84 white rats were used in the experiment. Diclofenac sodium was administered as a reference drug. Results and Discussion: An experiment on researching the impact of 5 samples of derivatives of 4.5-dihydroisoxazol-5-carboxamide on formalin oedema development among rats showed that the compound R001, compared with other substances studied, differs in the late onset of the therapeutic effect when ingested; the restoration of the foot volume to the initial level occurs only after the introduction of R005, R004 and R002. R005 to a greater extent than other compounds prevents the development of edema and has greater therapeutic efficacy than diclofenac sodium both with intragastric administration and subcutaneous injection. Conclusion: All five compounds in question showed anti-inflammatory activity, with the spectrum not so unequivocal both in qualitative and quantitative values.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139136165","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":"Modern possibilities of phytotherapy for male infertility from the standpoint of evidence-based medicine","authors":"O. Bratchikov, I. Tyuzikov, E. A. Grekov","doi":"10.18413/rrpharmacology.9.10060","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10060","url":null,"abstract":"Introduction: Male infertility is an topical medical and social problem of modern reproductive medicine. Its pharmacotherapy is often empirical in nature, and the most popular method remains the use of various herbal substances (phytotherapy), the effectiveness of which remains still understudied in the framework of evidence-based medicine. Materials and Methods: The results of research, thematic, systematic and Cochrane reviews and meta-analyses were searched in Medline/PubMed medical databases over the past 5 years using the search queries \"plants male infertility\", \"plants sperm\", \"phytotherapy male infertility\", \"phytomedicinal therapeutics male infertility\", \"systematic review\", \"meta-analysis\", and \"review\". Results: The vast majority of herbal substances offered for the treatment of male infertility demonstrate insufficient or contradictory evidence base for their clinical effectiveness, although some of them can be very useful pharmacotherapeutic options in the combined therapy of male infertility. Conclusion: Not all plant substances with a \"reproductive effect\" positioned in them actually have proven reproductive effects in studies in humans, therefore, the choice of phytotherapeutic agents in the treatment of idiopathic male infertility should be currently approached extremely carefully, especially in cases when we choose phytotherapy as an option for empirical monotherapy of male reproductive disorders.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139132887","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":"Neuroprotective properties of Na+/H+-exchanger isoform-1 inhibitor in experimental POAG","authors":"A. Pobeda, Alexander A. Spasov, O. Zhukovskaya, K. Shchurovskaya, N. V. Solovev, Valentina A. Kulikovskaya, V. M. Pokrovsky, E. A. Patrakhanov, Anastasia V. Turpakova, Anna I. Ustinova","doi":"10.18413/rrpharmacology.9.10058","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10058","url":null,"abstract":"Introduction: Worldwide glaucoma is the leading cause of irreversible vision loss. The processes associated with the loss of retinal ganglion cells are multifactorial and have much in common with neurodegenerative diseases. Therefore the search for means to prevent the death of retinal neurons is an important task of modern pharmacology.\u0000Materials and Methods: The study was conducted on male Wistar rats. Glaucoma was modeled by injecting a 1% solution of hyaluronic acid into the anterior chamber of the eye. The IOP level was recorded on the 0th, 63rd and 73rd days of the experiment. The effectiveness of the drugs was evaluated based on the results of ophthalmoscopy, electroretinography, followed by the determination of gene expression.\u0000Results and Discussion: In the group with RU-1355 correction, the fundus picture improved; the index in the group was 18.0% lower compared to the model. The introduction of the RU-1355 compound provided an increase in the a-wave amplitude by 18.1%, and b-wave amplitude by 39.0% relative to the group with pathology. The most pronounced effect was observed on the expression level of BDNF, Bcl-2, Caspase 3 and NF-κB p65, which indicates that the compound has the capacity to influence the slowdown of the apoptosis process through an increase in the neurotrophic factor and the anti-apoptotic factor Bcl-2.\u0000Conclusion: RU-1355 has neuroprotective properties, which was expressed by a decrease in ophthalmoscopic manifestations, preservation of the b-wave amplitude of the electroretinogram and the influence on gene expression of factors involved in apoptosis and neuroprotection. Based on the pharmacological activity of the RU-1355 compound in relation to POAG, further study of its action against other retinal diseases is promising.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138953304","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":"The EPOR/CD131 heteroreceptoragonist has an endothelioprotective effect against the background of pulmonary hypertension caused by monocrotalin","authors":"Lilia V. Korokina","doi":"10.18413/rrpharmacology.9.10057","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10057","url":null,"abstract":"Introduction: The abnormal increase in pulmonary pressure observed in pulmonary arterial hypertension (PAH) is a consequence of increased pulmonary vascular resistance due to progressive loss and obliteration of pulmonary arteries. The initial trigger is a combination of factors that lead to endothelial damage and impaired vascular regeneration. Aim: research the possibilities of pharmacological correction of pulmonary arterial hypertension induced by monocrotalin using the EPOR/CD131 heteroreceptor agonist with the laboratory code EP-11-3. Materials and Methods: The study of pharmacological activity on a model of monocrotaline induced PAH was carried out on male Sprague-Dawley rats weighing 180-220 grams. Monocrotaline (MCT) pulmonary hypertension was simulated in 30 animals using subcutaneous injection of MCT at a dose of 60 mg/kg. Seven days after the injection of MCT, the administration of the studied compounds began. The erythropoietin derivative with the laboratory code EP-11-3 and pHBSP administered subcutaneously at a dose of 25 mcg/kg once every 3 days for 21 days. Results: On the model of monocrotalin-induced PAH, it was shown that the erythropoietin derivative with the laboratory code EP-11-3 has a pronounced endothelioprotective effect, reducing the coefficient of endothelial dysfunction, statistically significantly increasing the expression of VEGF-R2 mRNA and reducing the expression of SDF-1 mRNA, reducing the concentrations of CT-1 and PNP, and reducing the signs of remodeling of the heart and pulmonary vessels. Conclusion: Erythropoietin derivative with laboratory code EP-11-3 has an endothelioprotective effect and reduces the manifestations of vascular remodeling in pulmonary hypertension caused by monocrotalin.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139210458","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":"Development of quantification methods of a new selective carbonic anhydrase II inhibitor in plasma and blood and study of the pharmacokinetics of its ophthalmic suspension in rats","authors":"A. L. Khokhlov, I. I. Yaichkov, Mikhail K. Korsakov, A. Shetnev, Nikita N. Volkhin, S. S. Petukhov","doi":"10.18413/rrpharmacology.9.10056","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10056","url":null,"abstract":"Introduction: Development of new bioanalytical methods is required for studying the systemic exposure of new selective inhibitor of carbonic anhydrase II, 4-(2-methyl-1,3-oxazole-5-yl)-benzenesulfonamide, and its N-hydroxymetabolite in plasma and in whole blood. The results of the experiment with a single administration of an ophthalmic suspension of the drug are necessary to optimize the subsequent design of a full pharmacokinetic study. Materials and Methods: HPLC-MS/MS method was used to measure a concentration of analytes in plasma and whole blood. Chromatographic separation was performed on the Poroshell 120EC-C18 column (50*3.0 mm, 2.7 µm). Pharmacokinetics was studied on 6 Wistar rats weighing 287.50±18.64 g (Mean±SD). Each animal was instilled with 40 µL of the ophthalmic suspension in concentration of 2% in each eye. Blood samples were collected before administration of the drug and 30 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, and 72 h after administration. Non-compartment approach was used for the evaluation of pharmacokinetic parameters. Results and Discussion: The protein precipitation was chosen for a sample preparation of biological fluids. A solution of ascorbic acid in concentration of 10% was added to plasma, and a solution of sodium thiosulfate in concentration of 10% was added to blood to prevent the degradation of N-hydroxymetabolite of the drug. The analytical range of determination of 4-(2-methyl-1,3-oxazole-5-yl)-benzenesulfonamide and its N-hydroxyderivative in blood was 50-10000 ng/mL and 5-1000 ng/mL, respectively, in plasma – 10-2000 ng/mL and 1-200 ng/mL, respectively. The maximum plasma concentration of the studied drug was 264.32±68.47 ng/mL (Mean±SD) 1.92±0.92 h (Mean±SD) after administration, and its metabolite was 10.43±1.79 ng/mL 2.17±1.13 h after administration. The maximum concentration of the drug in blood reached 8705.23±1301.84 ng/mL (Mean±SD) 1.17±0.52 h (Mean±SD) after administration, and the maximum concentration of N-hydroxymetabolite reached 230.00±69.54 ng/mL (Mean±SD) 1.33±0.41 h (Mean± SD) after administration. Conclusion: The developed methods have been fully validated according to the requirements of Russian and internatonal guidelines and have been successfully used for pharmacokinetic research. It was found that a content of 4-(2-methyl-1,3-oxazole-5-yl)-benzenesulfonamide and its main metabolite in whole blood is significantly higher than in plasma.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139247221","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":"Polyelectrolyte Microcapsules as a Tool to Enhance Photosensitizing Effect of Chlorin E6","authors":"E. P. Brodovskaya, L. A. Tararina, Mikhail N. Zharkov, Irina A. Khutorskaya, D. E. Yakobson, A. Al-khadj Aioub, I. Maev, A. V. Zaborovskiy, D. V. Yunina, S. V. Tsaregorodtsev, G. Sukhorukov, N. Pyataev","doi":"10.18413/rrpharmacology.9.10055","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10055","url":null,"abstract":"Introduction: Photodynamic therapy is a promising method of tumors treatment using photosensitizers and light of a certain wavelength. PS modification improves and enhances the phototoxic effect with decreased dark cytotoxicity. Materials and Methods: We compared the photosensitizing effect of polyelectrolyte microcapsules with chlorin E6 (ClE6) and free ClE6 at equivalent concentrations on murine fibroblast culture L929 using in vitro tests. Microcapsules were prepared layer by layer, sequentially depositing oppositely charged polyelectrolytes onto spherical CaCO3 particles. Cellular uptake of capsules was assessed using confocal microscopy. MTT test was used for a study of cell viability, and the relative amount of ROS was determined by the fluorescent method. Results: Microcapsules with ClE6 (in all tested concentrations) after exposure to red light (660 nm) reduced cell viability from 20% to 5%, while these capsules did not have dark cytotoxicity. Free ClE6 at the same concentrations as in the capsules after irradiation reduced viability from 65% to 35%. The level of ROS in the group of cells with capsules was 2 times higher compared to the group with CLE6. Discussion: The most probable mechanism of toxicity increase is creation of a higher ROS concentration and effect localization in the area of microcapsule interaction with the cell membrane. ROS production activation may stem from capsules providing a higher local PS concentration in the cell or nearby than the drug’s free form. Conclusion: The inclusion of chlorin E6 in polymer capsules reduced dark toxicity and increased the photosensitizing effect compared to the free form of ClE6.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139273241","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":"The influence of the vagus nerve and indole derivative SS-68 on excitation processes in the SA node","authors":"Anatoliy A. Nechepurenko, Pavel A. Galenko-Yaroshevsky, Vladimir M. Pokrovskiy, Anait V. Zelenskaya, Konstantin F. Suzdalev, Svetlana A. Lebedeva, Natalia M. Makhnova, Alexandr V. Maksemyuk, Ivan A. Minenko, Roman V. Nikitin, Valeriy G. Abushkevich†","doi":"10.18413/rrpharmacology.9.10054","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10054","url":null,"abstract":"Introduction: Atrial fibrillation (AF) is the most common form of cardiac arrhythmias. Studying the pathogenesis of this pathological process will make it possible to look for new methods of treating AF and to predict its occurrence in a more targeted way. The aim of the study was to identify the components of the takeover process of central rhythmogenesis by the SA node in the conditions of atrial fibrillation when stimulating the vagus nerve and using substance SS-68. Materials and Methods: The experiments were conducted on 30 frogs and 90 cats. In frogs, the activity of the regions of the medulla oblongata synchronous with the heart rhythm was determined in a high-frequency electromagnetic field. In cats, proximal and distal foci of luminescence in the vagus nerve (VN) and pools of pacemaker cells (PCs) in the sinoatrial node were visualized under topical and general anesthesia, using a KELSY scanner with a microscope video capture unit while stimulating VN and using SS-68. Results and Discussion: The stimulation of VN with volleys of electrical impulses and the introduction of SS-68 increase the foci of luminescence in the nerve and unite the PC pools. This way, under general anesthesia in comparison with topical anesthesia, the area of the proximal focus of VN luminescence decreased by 83.8%, and the distal focus – by 44.9%. Against the background of general anesthesia, the area of the proximal focus of luminescence when stimulating VN with volleys of electrical impulses was by 76.0% larger than before stimulation, and the distal focus – by 72.5%. After the administration of SS-68, there was an increase in the foci of luminescence: under general anesthesia, when compared with topical anesthesia, the area of the proximal foci of luminescence decreased by 86.8%, and the distal one – by 67.1%. Under general anesthesia, the area of the proximal focus of luminescence under conditions of stimulating VN with volleys of electrical impulses was by 82.2% larger than before stimulation and the distal one – by 78.2%. When signals from the brain arrive simultaneously through VN at the PC pools, they are absorbed by the PC pools; the focus of early depolarization becomes wide, which prevents the development of AF. The increased synchronizing influence of VN may be one of the methods for treating autonomic AF, and if its influence decreases, it can be a prognostic factor for the occurrence of recurrent AF. Conclusion: The tonic effect of VN on the heart rhythm through electrical stimulation of the former and the use of SS-68 is manifested in a decreased heart rate: the difference between the initial heart rhythm and the minimal synchronization range boundary. A decrease in the heart rate under the influence of VN prevents paroxysms of AF, but does not completely eliminate the influence of ectopic foci on it.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135086938","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":"Aversion-related effects of kappa-opioid agonist U-50488 on neural activity and functional connectivity between amygdala, ventral tegmental area, prefrontal cortex, hippocampus, and nucleus accumbens","authors":"Konstantin Y. Kalitin, Alexander A. Spasov, Olga Y. Mukha","doi":"10.18413/rrpharmacology.9.10051","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10051","url":null,"abstract":"Introduction: Among the various receptor systems in the brain, the opioid receptors have been the subject of extensive research due to their integral role in pain modulation, reward processing, and emotional regulation. The kappa-opioid receptor (KOR) system, in particular, stands apart due to its unique contribution to stress response, aversive behaviors, and dysphoric states. This paper aims to provide an understanding of the neural activity underlying the aversion-associated effects of the KOR agonist U-50488.&#x0D; Materials and Methods: Rats underwent stereotaxic surgery to implant electrodes into the amygdala, ventral tegmental area, prefrontal cortex, hippocampus, and nucleus accumbens. The rats were subjected to conditioned place preference test to measure aversion to U-50488. After that, local field potential (LFP) recordings were made. LFP data were processed and analyzed using spectral and coherence analysis methods. A stepwise multiple linear regression was employed to identify the LFP features most significantly correlated with aversion to U-50488.Results: The administration of U-50488 resulted in significant changes in LFP signals across multiple brain regions. These changes were particularly notable in the theta, gamma, and delta bands of brain waves (p<0.05). Theta and gamma activities were especially sensitive to the effects of U-50488. Connectivity calculations revealed shifts in coherence between brain regions, particularly highlighting the amygdala's involvement. While changes were also observed in the ventral tegmental area, prefrontal cortex, hippocampus, and nucleus accumbens (p<0.05), they contributed less to aversion. Using the stepwise multiple linear regression method, we established a final model with the 3 most significant variables: (1) coherence between the amygdala and medial prefrontal cortex, (2) coherence between the amygdala and hippocampus, and (3) theta power in the amygdala.&#x0D; Conclusion: Overall, the data provided insights into how electrical neural activity mediates aversion in response to KOR activation. The results showed that the severity of aversion can be reasonably predicted (r = 0.72±0.02, p = 0.0099) using LFP band power and functional connectivity data. We concluded that the amygdala is a brain region that contributes the most to the KOR agonist-induced aversion.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135393053","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}