Bekir Faruk Erden

Antidepressant-like effect of 7-nitroindazole in the forced swimming test in rats

Abstract Rationale: There is some strong evidence about the role of nitric oxide (NO) as an intercellular messenger in central physiological mechanisms. NO is synthesized from l-arginine by nitric oxide synthase (NOS), as a response to activation of N-methyl-d-aspartate (NMDA) receptors by excitatory amino acids. NMDA receptor antagonists also produce antidepressant-like actions in preclinical models. Objective: In the present study, the involvement of NO in the mechanism of depression was investigated. 7-Nitroindazole (7-NI) (15, 30, 60, 90 mg/kg IP), a selective inhibitor of neuronal NOS was examined. Methods: The Porsolt forced swimming test (FST) has been used as a test for screening new antidepressant agents. Results: 7-NI dose-dependently decreased the immobility time in FST, but produced no significant change in locomotor activity in naive rats. Neither l-arginine, nor d-arginine (100 mg/kg) affected the immobility time in the FST or revealed any effect on locomotion. l-Arginine but not d-arginine, given 10 min before 7-NI, reversed the 7-NI-induced effect on immobility time. Conclusion: Our findings suggest that NO might be an important modulator of depression in rats.

Anxiolytic-like effects of 7-nitroindazole in the rat plus-maze test.

It is considered that nitric oxide (NO) is one of the most interesting research subjects. Because the actual role of NO in the mechanism of anxiety is still unclear, in this study, the involvement of NO in the mechanism of anxiety was investigated, using the plus-maze test. 7-Nitroindazole (7-NI) (15, 30, 60, 90, and 120 mg/kg), a new nitric oxide synthase (NOS) inhibitor was studied. The time spent on open arms and open-arm visits was evaluated. 7-NI, at 15-120 mg/kg doses potently increased the time spent on open arms and open-arm visits. However, at 120 mg/kg it attenuated the time spent on the open arms, compared to at 90 mg/kg. This effect was attributed to decreased locomotor activity in the higher dose group. Neither L-arginine, nor D-arginine (100 mg/kg) significantly affected any of the behavioral parameters measured in the rat elevated plus-maze test. Neither drugs revealed any effect on locomotion. L-Arginine but not D-arginine given 10 min before 7-NI, reversed the 7-NI induced anxiolytic-like effects. These data support an involvement of NO in the process of anxiety, and further suggest that the anxiolytic-like effect of 7-NI may be attributable to the inhibition of NO synthesis.

Dextromethorphan attenuates ethanol withdrawal syndrome in rats.

The effects of dextromethorphan (DM), a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptors, have been investigated on ethanol withdrawal signs in rats. Ethanol (7.2% v/v) was given to rats in a liquid diet for 16 days. DM (10, 20, and 40 mg/kg) and saline were injected intraperitoneally at the third hour of ethanol withdrawal. DM (40 mg/kg) and ethanol dependent saline were also administered to ethanol naive rats. DM (40 mg/kg) did not produce any significant change in locomotor activity in ethanol naive rats. The effects of DM on locomotor activity and total ethanol withdrawal score were evaluated at the fourth and sixth hours of ethanol withdrawal. DM inhibited locomotor hyperactivity at these periods. DM also reduced total ethanol withdrawal score from the fourth hour to the sixth hour, and it significantly decreased audiogenic seizures. Seizure susceptibility after chronic ethanol exposure may be dependent upon sensitization or upregulation of NMDA processes and NMDA receptors. Our results suggest that inhibition of NMDA receptors by DM alleviates signs of ethanol withdrawal.

Blood pressure and vascular reactivity to endothelin-1, phenylephrine, serotonin, KCl and acetylcholine following chronic alcohol consumption in vitro

Ethanol has been reported to cause hypertension, the mechanism of which is unknown. Therefore, the effect of chronic ethanol consumption on vascular responsiveness and blood pressure was investigated. Systolic blood pressure was recorded weekly by tail‐cuff method. Aortic rings from rats fed chow ad libitum or pair‐fed liquid diets containing either ethanol (7.2% v/v) or isocaloric carbohydrate for 4 weeks were placed in organ chambers for isometric tension measurement. There was a mild but significant elevation of the systolic blood pressure in the alcohol‐fed rats by week 1 compared to baseline measurements and this remained higher. No significant changes in reactivity of rat isolated aortas to phenylephrine, serotonin, endothelin‐1 (ET‐1) and KCl were seen in chronic ethanol consumption. In addition, the sensitivity (i.e. pD2) of alcohol‐fed aortic rings to the vasoconstrictors was also unchanged compared to controls. Chronic ethanol consumption, however, increased relaxation to acetylcholine with increased pD2 values, but did not alter relaxation to sodium nitroprusside, a cyclic guanosine monophosphate (cGMP)‐dependent direct smooth muscle dilator. The results indicate that chronic ethanol consumption significantly potentiates endothelium‐dependent relaxations in aortic rings, probably through interference with the production and/or the release of nitric oxide (NO) or adaptive alterations in muscarinic receptors on the endothelial cells, and that increased vascular responsiveness to several vasoconstrictors is not a mechanism responsible for the blood pressure elevation in the chronic alcohol consumption in rats.

Antidepressant, anxiogenic, and antinociceptive properties of levofloxacin in rats and mice.

Levofloxacin, an optically active isomer of ofloxacin, is a fluorinated quinolone with a broad spectrum of antibacterial activity. Fluoroquinolones have been used for the treatment of bacterial infections for many years. Although they were considered as relatively safe drugs, various adverse effects have recently been reported along with increase in the usage of new-generation fluoroquinolones. In the present study, some of the central nervous system (CNS)-related side effects of levofloxacin were clarified in animals. Our results suggested that: levofloxacin (10-20-40 mg/kg i.p.) had no depression-like effect in the forced swimming test (FST) in rats; exerted anxiety-like effect in the elevated plus maze test in rats; did not alter the locomotor activity in rats; had no apparent effect on sleep latency but shortened the sleeping time on pentobarbital sleeping time in mice; and showed analgesic activity in acetic acid writhing and hot plate test in mice.

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.

Is arachis oil a solvent only, or does it also have an effect on the central nervous system?

Peanut (Archis hypogaea L.) seed, an important oil crop (arachis oil) throughout the world, is grown in large quantities in Africa, India and China. The oil is used in many edible products, including shortenings, margarines and mayonnaise, as a cooking and frying oil and as a salad oil. Arachis oil contains fatty acids and antioxidants. It has been shown to be unexpectedly atherogenic in the diets of experimental animals (Chow 1992). Moore et a1 (1993) have reported that 7-nitroindazole inhibits both ratand mouse-brain nitric oxide synthase and has potent anti-nociceptive activity in the mouse without significantly increasing blood pressure. 7-Nitroindazole is currently a promising and popular agent in the search for novel therapeutic compounds. Arachis oil is used as a vehicle for 7-nitroindazole and as a vehicle, carrier or solvent for other chemical substances such as 17fl-oestradi01, nandrolone decanoate, l ,25dihydroxyvitamin D3, acitretin and oestradiol benzoate. No data are available about the effects of this solvent on central nervous system function. In experiments involving 7-nitroindazole, only in the first study was saline used in six samples, as a control for arachis oil (Moore et a1 1993).

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

5-HT1 and 5-HT2 Receptors Are Involved in the Anxiolytic-Like Effects of the Neuronal NOS Inhibitor TRIM in the Rat

Preclinical Research