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    Effects of escitalopram on ethanol withdrawal syndrome in rats
    (PERGAMON-ELSEVIER SCIENCE LTD, 2006) Saglam, Esra; Kayir, Hakan; Celik, Turgay; Uzbay, Tayfun
    The present study was designed to investigate the effects of escitalopram, a selective serotonin reuptake inhibitor, on ethanol withdrawal syndrome in rats. Adult male Wistar rats (266-278 g) were subjects. Ethanol (7.2%, v/v) was given to rats by a liquid diet for 21 days. Control rats were pair fed with an isocaloric liquid diet containing sucrose as a caloric substitute to ethanol. Escitalopram, (2.5, 5 and 10 mg/kg) and saline were injected to rats intraperitoneally just before ethanol withdrawal. After the second and sixth hours of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs that included locomotor hyperactivity, agitation, stereotyped behavior, wet dog shakes, tremors and audiogenic seizures were recorded or rated. A second series of injections was given 30 min before sixth hour of withdrawal test. Effects of escitalopram on the locomotor activities of the naive (no ethanol-dependent) rats were also evaluated. Escitalopram (5 mg/kg) reduced the increased stereotyped behaviors at the sixth hour of ethanol withdrawal. It inhibited tremors at the second hour of ethanol withdrawal at doses of 5 and 10 mg/kg. Escitalopram (2.5 and 5 mg/kg) also produced some significant attenuations in the incidence of wet dog shakes at the second and sixth hours of the observation period. It was found ineffective on locomotor hyperactivity, agitation and audiogenic seizures. Escitalopram (2.5 and 5 mg/kg) did not cause any significant effect on locomotor activities of the naive rats. Our results suggest that acute escitalopram treatment has some limited beneficial effects on ethanol withdrawal syndrome in rats. (c) 2006 Elsevier Inc. All rights reserved.
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    Effects of olanzapine on ethanol withdrawal syndrome in rats
    (ELSEVIER SCIENCE BV, 2008) Unsalan, Nasibe; Saglam, Esra; Kayir, Hakan; Uzbay, Tayfun
    The present study was designed to investigate the effects of olanzapine, a serotonin-dopamine antagonistic atypical antipsychotic agent, on ethanol withdrawal syndrome in rats. Adult male Wistar rats were subjects. Ethanol (7.2%, v/v) was given to rats by a liquid diet for 21 days. Control rats were pair fed with an isocaloric liquid diet containing sucrose as a caloric substitute to ethanol. After 2nd, 4th and 6th h of ethanol withdrawal, rats were observed for 5 min, afterwards withdrawal signs that included locomotor hyperactivity, agitation, stereotyped behavior, tremor, wet dog shakes, abnormal posture and abnormal gait were recorded or rated. Olanzapine (0.5, 1 and 2 mg/kg) and saline were injected to the rats intraperitoneally 30 min before ethanol withdrawal assessment. A second series of injections was also given 30 rain before the 6th-h-observation, and subjects were then tested for audiogenic seizures. Olanzapine (2 mg/kg) produced significant inhibitory effects on stereotyped behaviors and wet dog shakes at the 6th h of ethanol withdrawal. Contrary, the same dose caused some increases in the intensity of posture and gait impairments at the 2nd h of ethanol withdrawal. In addition, that dose was found to be ineffective on agitation, tremor, tail stiffness and audiogenic seizures. Our results suggest that acute olanzapine treatment has beneficial effects on stereotyped behavior and wet dog shakes, but it also has some adverse effects on posture and gait during ethanol withdrawal in rats. Overall, olanzapine does not seem to be an adequate and suitable drug in controlling of ethanol withdrawal syndrome. (c) 2007 Elsevier B.V. All rights reserved.
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    Escitalopram increases cortical nitric oxide synthase (NOS) in rat brain during ethanol withdrawal
    (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2008) Saglam, Esra; Ates, Lora Esberk; Kayir, Hakan; Celik, Turgay; Terzioglu, Berna; Uzbay, Tayfun
    The effect of escitalopram on ethanol withdrawal syndrome (EWS) and involvement of nitric oxide system in rats was investigated. Male Wistar rats divided into five experimental groups of eight animals each: (a) control group; (b) EWS (saline) group; (c) escitalopram 2.5 mg group; (d) escitalopram 5 mg group and (e) escitalopram 10 mg group. Ethanol dependence was induced in rats by ethanol-containing liquid diet and ethanol withdrawal was precipitated by replacing ethanol free diet. Ethanol receiving rats in individual groups were decapitated on 21st day of ethanol ingestion and at sixth hour of ethanol withdrawal. Brains were removed and dissected. Five regions of the brain were dissected: the frontal cortex, cerebellum, striatum, hippocampus and hypothalamus. Immunohistochemical NOS staining was performed. The NOS staining intensity in cortex and hypothalamus regions were significantly lower in EWS group than control group. During EWS period, in rats given 2.5 and 10 mg/kg escitalopram, the staining intensity in cortex, striatum and hippocampus were found to be 11.492, 8.519 and 11.234, respectively, and was statistically different than the control group. The hippocampal NOS staining intensity was found to be significantly decreased with 2.5 mg/kg escitalopram, whereas the cortex, striatum and hippocampal staining intensity were increased significantly with 5 mg/kg. In 10 mg/kg escitalopram group, staining properties were not different than those of the control group. Our results suggest that NOS decreases during ethanol withdrawal in cortex and hypothalamus of rat brain and treatment with escitalopram reverses the enzyme density in cortex but not hypothalamus. (c) 2008 Elsevier Inc. All rights reserved.
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    The prevention of myocardial ultrastructural changes by perindopril, atenolol and amlodipine in chronic alcohol administered rats
    (Elsevier, 2006) Sağ, Cemal; Yokuşoğlu, Mehmet; Özkan, Mustafa; Kayır, Hakan; Uzun, Mehmet; Baykal, Barış; Özoğul, Candan; Baysan, Oben; Uzbay, Tayfun
    The effects of perindopril, an angiotensin converting enzyme inhibitor, atenolol, a beta adrenergic receptor blocker and amlodipine, a calcium channel blocker were investigated in chronic alcohol administered rats. Adult male Wistar rats (240–320 g) were used in the present study. Alcohol was given to rats by a modified liquid diet for 21 days. Perindopril (2.5 and 5 mg kg?1), atenolol (5 and 10 mg kg?1) and amlodipine (5 and 10 mg kg?1) were injected to rats in different groups intraperitoneally for 21 days. Control rats were pair fed by an isocaloric liquid diet containing sucrose as a caloric substitute for alcohol. Saline was injected to control rats for 21 days. Rats were anesthetized with ether. Their hearts were removed and 1 mm3 samples from left ventricles were fixed. Five fields per heart were examined and photographed with transmission electron microscope. Blood alcohol levels were also measured spectrophotometrically. Daily alcohol consumption of the rats was in a range of 12.09–15.5 g kg?1. Blood alcohol concentrations were found as 145.63 mg dl?1 at 21st day of alcohol consumption. Chronic alcohol consumption caused some marked myocardial injuries. Perindopril and atenolol but not amlodipine produced some significant beneficial effects on alcohol-induced myocardial damages. Our results imply that perindopril and atenolol but not amlodipine have protective effects on heavy chronic alcohol consumption-induced myocardial injury in rats.