Mehmet Emin Buyukokuroglu

Involvement of serotonin receptor subtypes in the antidepressant-like effect of beta receptor agonist Amibegron (SR 58611A): An experimental study

New therapeutic strategies against depression, with less side effects and thus greater efficacy in larger proportion of depressed patients, are needed. Amibegron (SR58611A) is the first selective β3 adrenergic agent that has been shown to possess a profile of antidepressant activity in rodents. To investigate the involvement of serotonin receptors in the effects of amibegron, we used the serotonin 5HT1A receptor antagonist WAY-100635 (WAY) or serotonin 5HT2A-2C receptor antagonist ketanserin or serotonin 5HT3 receptor antagonist ondansetron in mice forced swimming test (FST). The locomotor activity was evaluated by measuring the total distance moved in the apparatus and the speed of the animals in the open field test. Imipramine (30mg/kg) significantly reduced immobility time compared to vehicle-treated group while amibegron (5 and 10mg/kg) dose dependently reduced immobility time in the FST. WAY(0.1mg/kg), ondansetron (1mg/kg), ketanserin(5mg/kg) had no effect on immobility time in naive mice while all of the drugs partially and significantly reversed amibegron (10mg/kg) induced decreasement in the immobility time in FST. None of the drugs alter locomotor activity in the open field test. The antidepressant-like effect of amibegron in the FST seems to be mediated by an interaction with serotonin 5-HT1A, serotonin 5-HT2A-2C and serotonin 5-HT3 receptors.

Evidence that the anxiolytic-like effects of the beta3 receptor agonist Amibegron involve serotoninergic receptor activity

Anxiety disorders are the most common behavioral disorders, and they exhibit high comorbidity rates. The aim of the present study was to confirm the effects of Amibegron, the first selective beta 3 adrenergic agent, on anxiety and to demonstrate that different serotoninergic receptor subtypes are involved in this effect. We administered the serotonin 5-HT1A receptor antagonist WAY-100635, the serotonin 5-HT2A receptor antagonist Ketanserin and the serotonin 5-HT3 receptor antagonist Ondansetron in mice and evaluated their performance in the elevated plus-maze test. Mice administered with Amibegron (5 and 10 mg/kg) showed a dose-dependent prolonged time spent in the open arms and an increase in the number of entries into the open arms during the elevated plus-maze (EPM) test. However, in the control mice, administration of WAY, Ketanserin and Ondansetron demonstrated no effect on the time spent in the open arms and the number of entries into the open arms. In addition, these treatments all significantly reversed the effect of the Amibegron-induced (10 mg/kg) increase in the time spent in the open arms. However, only WAY and Ketanserin treatments reversed the Amibegron-induced increase in the number of entries into the open arms. In conclusion, Amibegron exerted a significant anxiolytic effect, which was as effective as Diazepam, in mice during the EPM test. This effect of Amibegron may be mediated by interactions with the serotonin 5-HT1A, 5-HT2A and 5-HT3 receptors.

In vivo anti-ulcerogenic effect of okra (Abelmoschus esculentus) on ethanol-induced acute gastric mucosal lesions

Abstract Context: Okra, Abelmoschus esculentus (L.) (Malvaceae), is a medicinal plant widely used in Turkish traditional medicine for the treatment of various diseases such as ulcers and gastritis. Objective: In the present study, we evaluated the gastroprotective effect of okra against ethanol-induced acute gastric mucosal injury in animal models. Materials and methods: Wistar rats were treated with 500, 250 or 100 mg/kg okra; 20 mg/kg famotidine (Fam); and 75 mg/kg quercetin (Que). Following a 60 min period, all the rats were given 1 mL of ethanol (80%). One hour after the administration of ethanol, all groups were sacrificed. Results: At 5000 mg/kg, the extract produced (okra) no signs of toxicity in animals. Okra 500, 250, 100, Fam 20 and Que 75 inhibited ulcer formation by 81.0, 67.5, 67.0, 76.3 and 72.4%, respectively. Okra 500 significantly decreased edema, hemorrhage and inflammation scores compared with the ethanol group (p < 0.05). The oxidant levels decreased significantly in the all study groups compared within ethanol group (p < 0.001). Serum β-carotene and retinol levels significantly increased 40.2 and 45.4% in the okra 500 group. In okra 500, 250 and Fam 20 groups, apoptosis significantly decreased (p < 0.001), while okra 500, 250 and Fam 20 groups showed a higher percentage of cell proliferation compared with the ethanol group (p < 0.001). Discussion and conclusions: Our in vivo data indicate that okra has a gastroprotective effect against ethanol and could reduce the gastric ulcer as seen from biochemical and histopathological results. We suggest that okra could be a possible therapeutic antiulcer agent.

PS124. Effects of desipramine, venlafaxine and bupropion on depression and anxiety in the forced swimming test and elevated plus maze test in mice

Specific objective of the study: This study is aimed to investigate desipramine, venlafaxine and bupropion on depression and anxiety in mice. Methods used: We used a classic tricyclic antidepressant, desipramine; a serotonin-norepinephrine reuptake inhibitör, venlafaxine; a second-generation antidepressant agent that blocks centrally the reuptake of noradrenaline and dopamine, bupropion in forced swimming test (FST), elevated plus maze test (EPM) and open field test. Summary of results: Imipramine (30 mg/kg), desipramine (7.5 mg/kg and 15 mg/kg), venlafaxine (4 mg/kg and 8 mg/kg), bupropion (20 mg/kg and 40 mg/kg) significantly reduced immobility time dose dependently, compared to vehicle-treated group. And also bupropion (40 mg/kg) exerted significant antidepressant-like effects in the mice FST which was more effective than imipramine. Diazepam (2 mg/kg), desipramine (7.5 mg/kg and 15 mg/kg), venlafaxine (4 mg/kg and 8 mg/kg), bupropion (20 mg/kg and 40 mg/ kg) significantly increased the time spent in the open arms dose dependently, compared to the vehicle-treated group. Diazepam (2 mg/kg), desipramine (7.5 mg/kg and 15 mg/kg), venlafaxine 8 mg/kg) and bupropion (20 mg/kg and 40 mg/kg) significantly increased the number of entries into the open arms, compared to the vehicle-treated group. And also bupropion (40 mg/kg) exerted significant anxiolytic-like effects in the mice EPM test which was more effective than diazepam. None of the drugs modified the total distance moved in the open field test. Conclusions reached: desipramine, venlafaxine and bupropion (20 mg/kg) exerted significant antidepressant-like effects which was as effective as imipramine. And also bupropion (40 mg/kg) exerted significant antidepressant-like effects which was more effective than imipramine. Again, desipramine, venlafaxine and bupropion (20 mg/kg) exerted significant anxiolytic-like effects which was as effective as diazepam. And also bupropion (40 mg/ kg) exerted significant anxiolytic-like effects which was more effective than diazepam. PS125 Functional and morphological changes induced by ketamine in the hippocampus Giulia Treccani1,2, Nico Liebenberg N1, Sandra Tillmann1, Laura Musazzi2, Marco Milanese3, Fenghua Chen4, Betina Elfving1, Gregers Wegener1,5, Jens Randel Nyengaard4, Maurizio Popoli2, Heidi Kaastrup Müller1. 1 Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark 2 Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmacologiche e Biomolecolari and Center of Excellence on Neurodegenerative Diseases (CEND), Università degli Studi di Milano, Milan, Italy 3 Department of Pharmacy, Unit of Pharmacology and Toxicology, University of Genova, Genoa, Italy. 4 Stereology and Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University Hospital, Aarhus, Denmark 5 Pharmaceutical Research Center of Excellence, School of Pharmacy, North-West University, Potchefstroom, South