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    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, Hülya
    Current 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.
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    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, Oruç
    Alcohol 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.
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    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 Gökhan
    Alcohol 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.