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Öğe Effects of artemisinin on anti-epileptogenic, antioxidant and cholinesterase enzymes in pentylenetetrazole-induced kindling model in mice(Association Pharmaceutical Teachers India, 2023) Koçak, Yılmaz; Yunusoğlu, Oruç; Huyut, Zübeyir; Türkan, FikretBackground: Artemisinin (ART) is a compound synthesized from the plant Artemisia annua. This compound has various therapeutic effects and is widely used against malaria. However, ART is known to have modulating effects on GABA (gamma-aminobutyric acid) receptors, which are thought to be responsible for epileptic seizures. This study aimed to evaluate the effects of ART on anti-convulsant, antioxidant, and cholinesterase enzyme activities in Pentylenetetrazole (PTZ)-induced kindling model in mice. Materials and Methods: In the experiment, 6 groups were formed, with seven mice in each group. Mice received a total of 11 intraperitoneal injections of PTZ (35 mg/kg). On the last day of the study, a threat dose of PTZ (75 mg/kg) was administered. In addition, behavioral analysis tests (Locomotor activity and rotarod) and biochemical measurements were performed. Results: Compared with the PTZ group, ART attenuated the severity of the kindling, decreasing the seizure score. ART and VPA reversed increased oxidative stress. Decreased cholinesterase enzymes in PTZ-induced brain increased with ART treatment. While the PTZ application impaired locomotor activity in mice, the ART application provided improvement in locomotor activity. However, no significant difference was found between the groups in the motor performance of the mice. Conclusion:The findings show that ART may have the potential to prevent PTZ-induced oxidative stress, neurochemical changes, behavioral disorders, and seizures.Öğe The effects of moxidectin nicotine-conditioned cue on nicotine-seeking behavior in mice(Inst Advanced Science Extension, 2021) Yunusoğlu, Oruç; Demirkol, Muhammed Hamdi; Berköz, Mehmet; Sağmanlıgil, Vedat; Oto, Gökhan; Özdemir, HülyaCurrent pharmacotherapies for nicotine abuse are few and relatively inefficient demonstrating the need for the development of new, effective remedies. Moxidectin is used as an anti-parasitic agent in both animals and humans, it also activates GABA receptors. The objective of the present investigation was to study the effect of moxidectin on nicotine-induced conditioned place preference (CPP) in male Swiss mice. Intraperitoneal (i.p.) route was used for nicotine (0.5mg/kg) administration for a 3-day conditioning program. The influences of moxidectin on the reinforcing characteristics of nicotine were tested in mice given i.p. treatment of moxidectin (5 and 10mg/kg) 30 minutes prior to per nicotine administration. CPP was extinguished by repeated testing, through which conditioned mice were daily given two doses of moxidectin (5 and 10mg/kg, i.p.). Subsequently, the potency of moxidectin in blocking the reinstatement of CPP provoked by priming given low-dose nicotine (0.1mg/kg, i.p.) was also evaluated. Moxidectin treatment illustrated a reserve of acquisition of nicotine-induced CPP. It was reduced priming nicotine-induced reinstatement and accelerated the extinction of CPP. Relatively nicotine enhanced the locomotor, motor activity but was not statistically significant. In conclusion, the outcomes demonstrate the potential for the development of moxidectin as a new pharmacotherapy for the treatment of nicotine addiction. (C) 2021 The Authors. Published by IASE.Öğe Evaluation of the effects of quercetin on the rewarding property of ethanol in mice(Elsevier Ireland Ltd, 2022) Yunusoğlu, OruçBackground: The flavonoid quercetin has several pharmacological effects on the nervous system. Previous research showed that quercetin has useful influences on some mechanisms that are relevant in drug and substance addiction. Alcohol addiction, also known as alcoholism, is a disorder that influences the population in all walks of life. The purpose of the current study was to investigate whether quercetin affects the acquisition, extinction, and reinstatement of ethanol-induced conditioned place preference (ethanol-CPP) in adolescent mice. Methods: CPP was established by administration of intraperitoneal (i.p.) ethanol (2.0 g/kg) in a conditioning trial. The mice were pretreated with quercetin (at doses of 10, 30, and 100 mg/kg, i.p.) 30 minutes before each ethanol injection to test the effects of quercetin on the reward properties of ethanol. Ethanol-CPP was extinguished (13days) by repeated testing, during which conditioned mice were given different doses of quercetin every day. Lastly, efficacy of quercetin in preventing reinstatement of ethanol-CPP triggers was also assessed by the administration of single dose ethanol (0.4 g/kg, i.p.). Results: Quercetin pretreatment attenuated the acquisition and reinstatement. In addition, quercetin administration accelerated the extinction of ethanol-CPP. Conclusions: In conclusion, these results may cast a novel light on quercetin as an agent that could be potentially useful to attenuate different effects of ethanol and as adjuvant pharmacotherapy for ethanol addiction. However, future studies are needed to demonstrate the detailed underlying mechanisms of quercetin on ethanol addiction.Öğe The first electroanalytical study of umifenovir (Arbidol) used as a potential antiviral drug for the treatment of SARS-CoV-2: A voltammetric quantification on the boron-doped diamond electrode by using anionic surfactant media(Electrochemical Soc Inc, 2023) Özok, Hande İzem; Kıran, Musa; Yunusoğlu, Oruç; Yardım, YavuzIn this work, an electroanalytical procedure for sensing umifenovir (arbidol) by square wave adsorptive stripping voltammetry (SW-AdSV) was developed utilizing an anodically pretreated boron-doped diamond electrode. Measurements of umifenovir using cyclic voltammetry with phosphate buffer solution (PBS, 0.1 M, pH 2.5) revealed irreversible behaviour, adsorption-controlled as well as an ill-defined (+1.13 V, P-A1) and a well-defined (+1.47 V, P-A2) two oxidation peaks. Umifenovir oxidations depend critically on supporting electrolytes and pH. The second oxidation peak (P-A2) current of the umifenovir was enhanced by adding sodium dodecyl sulfate (SDS, anionic surfactant) in the chosen supporting electrolyte. Umifenovir was quantified using its second oxidation peak (P-A2) at about +1.39 V. Using the optimized condition, the oxidation peak current of P-A2 showed a linear relationship for umifenovir determination in the concentration range from 0.005 to 1.0 mu g ml(-1) (9.73 x 10(-9)-1.95 x 10(-6) M), with a detection limit of 0.0014 mu g ml(-1) (2.72 x 10(-9) M) in PBS (PH 2.5) with SDS. Finally, the developed approach was successfully utilized to determine umifenovir in the pharmaceutical formulation and urine samples. To the best of our knowledge, this is the first electroanalytical approach for voltammetric sensing of umifenovir.Öğe Influence of selective dopamine agonist ropinirole on conditioned place preference and somatic signs of morphine withdrawal in rats(Frontiers Media SA, 2022) Shahzadi, Andlee; Yunusoğlu, Oruç; Karabulut, Enes; Sönmez, Haktan; Yazıcı, ZelihaThe underlying mechanism of dependence and rewarding effects of morphine is imperative to understand. The primary aim of this study was to investigate whether ropinirole D2/3 agonist affects the rewarding and reinforcing properties of morphine-induced conditioned place preference (CPP) and withdrawal syndromes in rats. On day one, the animals were randomly divided to conduct the pre-test. The morphine (10 mg/kg, i.p.) and/or saline was administered on alternate days in an 8-day CPP session. On day 10, 15 min prior to the post-conditioning test (expression), a single dose of ropinirole (1, 2, and 5 mg/kg, i.p.) was given to rats. In extinction session, ropinirole was injected daily, and CPP was extinguished by repeated testing, with intervals of 3 days. Finally, reinstatement was assessed by administering ropinirole (1, 2, and 5 mg/kg) 15 min before the morphine injection. Morphine dependence was developed by administering increasing doses of morphine (10-50 mg/kg, i.p.). To assess withdrawal symptoms, ropinirole (1, 2, and 5 mg/kg) was injected 15 min before naloxone (2 mg/kg, s.c.) administration. The present study confirms that ropinirole attenuates expression and reinstatement of CPP, while it precipitates the extinction of morphine-induced CPP. Naloxone-precipitated morphine withdrawal symptoms, including wet dog shakes and weight loss, were attenuated although jumping was increased by a single ropinirole injection. Thus, ropinirole was influential in attenuating expression, reducing drug seeking and weakening reinstatement via the dopaminergic system. These findings show that ropinirole might affect neuro-adaptive changes related to dependence.Öğe Investigation of the impact of antiparasitic drug moxidectin on the rewarding effects of alcohol(Aepress Sro, 2022) Ekici, Abdurrahman; Gürbüz, Esra; Berköz, Mehmet; Türkmen, Ömer; Başbuğan, Yıldıray; Yunusoğlu, OruçAlcohol addiction or alcoholism constitutes a significant risk factor worldwide for morbidity and mortality. Moxidectin is a recently approved anthelmintic drug, which also activates the gamma-aminobutyric acid receptors. The objective of the present study was to examine the impact of moxidectin on rewarding effects of ethanol in the conditioned place preference (CPP) model in mice. In separate experiments, mice were administered intraperitoneal (i.p.) injections of moxidectin (5 or 10 mg/kg) before a) acquisition of alcohol-induced CPP, b) each extinction session, and c) alcohol-induced reinstatement of CPP. The present experiments provide consistent data about ethanol place preference in mice (2 g/kg, i.p.), with mice in all tests spending significantly more time on the ethanol-paired side. The acquisition of the CPP response to ethanol was prevented by the administration of moxidectin at a dose of 10 mg/kg. Additionally, moxidectin treatment accelerated the extinction of ethanol CPP when given repeatedly during the extinction phase. Ethanol-induced reinstatement of CPP following an extinction phase was inhibited by moxidectin. Ethanol alone and co-administration with moxidectin did not change locomotor activity and motor coordination. In conclusion, we suggest that moxidectin may be a promising therapeutic candidate for prevention of ethanol-induced addiction and relapse as well as detoxification.Öğe Investigation of the pharmacological potential of myricetin on alcohol addiction in mice(Marmara University, 2022) Yunusoğlu, Oruç; Shahzadi, Andleeb; Türel, Canan Akünal; Demirkol, Muhammed Hamdi; Berköz, Mehmet; Akkan, Ahmet GökhanAlcohol addiction is one of the leading causes which is associated with morbidity and mortality with outcomes in high healthcare and economic costs. Myricetin is a flavonoid that demonstrates therapeutic actions in many central nervous system diseases. In the current study, the conditioned place preference (CPP) tests were performed W examine the effects of myricetin on ethanol reward. During conditioning, intraperitoneal (i.p) administration of ethanol (2 g/kg) and serum physiologic were given on alternate days for 8 days. In order to evaluate the effect of myricetin on the development of alcohol addiction, myricetin was injected into mice 30 minutes before ethanol administration. Subsequently, a daily myricetin injection was performed to evaluate the effect of myricetin on the extinction of alcohol addiction. Finally, ethanol was administered 900 seconds after different dose myricetin administration, and reinstatement was evaluated immediately thereafter. Systemic ethanol (2 g/kg, i.p) administration significantly produced CPP. Myricetin (5 and 10 mg/kg, i.p) attenuated the development of ethanol addiction (p < 0.05). Systemic myricetin injections immediately after each extinction period precipitated extinction and decreased reinstatement (10 mg/kg, i.p, p < 0.05, respectively). Ethanol alone and in combination with myricetin did not change locomotor activity and motor coordination. As a result, it can be suggested that myricetin is effective in attenuating the rewarding effect of alcohol in mice and can be used for the adjunctive therapy for alcohol addiction. In addition, it will be appropriate to conduct mechanistic experimental studies regarding these results in the future.Öğe Investigation of the pharmacological, behavioral and biochemical effects of boron on rats with rotenone-induced Parkinson's Disease(Cellular and Molecular Biology Association, 2023) Özdemir, Hülya Sağmanlıgil; Yunusoğlu, Oruç; Sağmanlıgil, Vedat; Yaşar, Semih; Çölçimen, Neşe; Göçeroğlu, Rezzan Temelli; Çatalkaya, EgeParkinson's disease (PD) is a progressive neurodegenerative disorder of the central nervous system. In different studies, it has been investigated that boric acid has positive effects on different mechanisms that are important in PD. The aim of our study was to investigate the pharmacological, behavioral and biochemical effects of boric acid on rats with experimental PD with Rotenone. For this purpose, Wistar-albino rats were divided into 6 groups. Only normal saline was applied subcutaneously (s.c) to the first control and sunflower oil to the second control group. Rotenone was administered (s.c) to 4 groups (groups 3-6) at a dose of 2 mg/kg for 21 days. Only rotenone (2mg/kg, s.c) was administered to the third group. Boric acid was administered intraperitoneally (i.p.) at 5 mg/kg, 10 mg/kg, and 20 mg/kg to groups 4, 5, and 6, respectively. During the study, behavioral tests were applied to the rats, and then histopathological and biochemical analyzes were performed from the sacrificed tissues. According to the data obtained, a statistically significant difference (p<0.05) was observed between the Parkinson's group and the other groups in motor behavior tests, excluding the catalepsy test. Boric acid exhibited dose-dependent antioxidant activity. As a result of the histopathological and immunohistochemical (IHC) examination, a decrease in neuronal degeneration was observed at the increasing doses of boric acid, while gliosis and focal encephalomalacia were rarely encountered. There was a significant increase in tyrosine hydroxylase (TH) immunoreactivity, especially in group 6, with a dose of 20 mg/kg of boric acid. From these results, we conclude that the dose-dependent effect of boric acid may protect the dopaminergic system with antioxidant activity in the pathogenesis of PD. However, the effectiveness of boric acid on PD needs further investigation in a larger, more detailed study using different methods. Copyright: © 2022 by the C.M.B. Association. All rights reserved.Öğe Oleanolic acid suppresses pentylenetetrazole-induced seizure in vivo(Taylor & Francis Ltd, 2023) Türel, Canan Akünal; Yunusoğlu, OruçThe aim of this study was to investigate the protective effects of triterpene oleanolic acid on the brain tissue of mice with pentylenetetrazole (PTZ)-induced epileptic seizures. Male Swiss albino mice were randomly separated into five groups as the PTZ, control, and oleanolic acid (10, 30, and 100 mg/kg) groups. PTZ injection was seen to cause significant seizures compared with the control group. Oleanolic acid significantly prolonged the latency to onset of myoclonic jerks and the duration of clonic convulsions, and decreased mean seizure scores following PTZ administration. Pretreatment with oleanolic acid also led to an increase in antioxidant enzyme activity (CAT and AChE) and levels (GSH and SOD) in the brain. The data obtained from this study support oleanolic acid may have anticonvulsant potential in PTZ-induced seizures, prevent oxidative stress and protect against cognitive disturbances. These results may provide useful information for the inclusion of oleanolic acid in epilepsy treatment.Öğe Resveratrol inhibits nicotine-induced conditioned place preference in mice(Univ Sao Paulo, Conjunto Quimicas, 2023) Yunusoğlu, OruçNicotine addiction leads to in a huge burden on public health and the economy worldwide. Resveratrol (3,5,4'-tetrahydroxystilbene) is the most well-known polyphenolic stilbenoid. Resveratrol was shown to exhibit positive effects on numerous mechanisms that are important for drug and substance addiction. Thus, this study aimed to examine the effect of resveratrol on nicotine addiction. Intraperitoneal (i.p.) treatment with nicotine (0.5 mg/kg) significantly enhanced time spent in the nicotine-paired compartment. Resveratrol (50 and 75 mg/kg, i.p.) and varenicline (2 mg/kg, i.p.) co-administered with nicotine during the 3-day conditioning period effectively diminished the acquisition of nicotine-induced conditioned place preference (CPP). On the other hand, the administration of resveratrol (50 and 75 mg/kg, i.p.) and varenicline (2 mg/kg, i.p.) decreased the low dose (0.1 mg/kg, i.p.) nicotine-induced reinstatement. The results suggest that resveratrol and varenicline inhibit the acquisition and reinstatement of nicotine's reward properties. Resveratrol displayed similar results in the CPP phases as obtained with the reference drug varenicline. In conclusion, resveratrol could be beneficial as an adjuvant pharmacotherapy for nicotine addiction; however, more investigation is needed to completely explain this property.Öğe Rewarding effect of ethanol-induced conditioned place preference in mice: Effect of the monoterpenoid linalool(Elsevier Science Inc, 2022) Yunusoğlu, OruçAlcohol addiction is a chronic relapsing disease that is progressive and has severe detrimental health outcomes. The use of natural products has become popular for the treatment of side effects of drugs and substance abuse. Linalool is a monoterpenoid that exhibits several effects on the central nervous system. Linalool was identified to have beneficial effects on different mechanisms that are relevant in drug addiction or substance use disorder. The primary aim of the present study was to evaluate the therapeutic effect of linalool on the rewarding properties of alcohol in mice. Conditioned place preference (CPP) was established by intraperitoneal (i.p.) injection of ethanol (2 g/kg) during an 8-day conditioning trial. The effects of acamprosate and linalool on the rewarding properties of ethanol were tested in mice who received linalool (12.5, 25, and 50 mg/kg, i.p.) and acamprosate (300 mg/kg, i.p.) 30 min before each ethanol injection. CPP was extinguished by repeated testing, throughout which conditioned mice were administered daily linalool. Mice were lastly examined for reinstatement provoked by i.p. administration of single low-dose ethanol (0.4 g/kg, i.p.). Treatment with linalool reduced the acquisition and reinstatement, and precipitated the extinction of ethanol-induced CPP in mice. Acquisition and reinstatement of alcohol-induced CPP were significantly reduced by acamprosate, which also precipitated extinction. Ethanol alone and the combination with linalool or acamprosate did not alter locomotor activity. The results of this study suggest that linalool may have pharmacological effects for the treatment of alcohol addiction. In addition, further investigation is required to fully explore the benefits and possible adverse effects of linalool on alcohol addiction. (C) 2021 Elsevier Inc.
