Browsing by Author "Uzbay, Tayfun"

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Assessing empathy like social behavior in valproic acid induced autism model of rats
(Wiley, 2019-12-01) Uzbay, Tayfun; Öz, Pınar; Tuncak, Süeda; TUNÇAK, SÜEDA; Gören, Bülent; GÖREN, BÜLENT; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; 0000-0002-9784-5637; ABC-5283-2020; AAH-1718-2021; AAH-1734-2021
Audiogenic seizures potentiate hippocampal neuronal loss in ethanol-dependent rats
(Journal Neurological Sciences, 2014) Yılmaz, İsmail; Nilüfer Yonguç, Gökşin; Tosun, Serkan; Kayır, Hakan; Uzbay, Tayfun
Objective: Audiogenic seizure (AS) susceptibility is observed following withdrawal from chronic ethanol treatment in rodents. This is the first study to investigate and compare the effects of ethanol withdrawal on the hippocampal formation in AS appeared and nonappeared animals. Material and Methods: Adult male Wistar rats (225-320 g) were used. Ethanol was given to rats in a modified liquid diet for twenty days. Daily ethanol consumption was in a range of 10.35 +/- 1.25 to 15.20 +/- 0.79 g/kg during the exposure to ethanol (7.2%). At the end of exposure to a 7.2% ethanol-containing liquid diet, ethanol was withdrawn and withdrawal signs were recorded or rated. Increased stereotyped behavior, wet dog shakes, agitation, tail-stiffness and abnormal posture and gait appeared during ethanol withdrawal in dependent rats. AS was also induced in 5 of 11 of ethanol dependent rats. Following audiogenic stimuli, rats were decapitated and their brains were removed. Neuron counts from pyramidal cell layers in CA1 and CA2-3 regions of the hippocampus were obtained from control rats and ethanoldependent rats with and without audiogenic seizure. Results: Significant neuronal losses were found in CA1 and CA2-3 regions of the hippocampal formation in the ethanol-dependent group. Neuronal loses in AS appeared group were significantly more than in AS non-appeared group. Conclusions: ASs during ethanol withdrawal significantly potentiated neuronal degeneration in all subdivisions of the CA area of the hippocampal formation in rats. Thus, prevention of seizures in alcoholic individuals may be important for protection from excessive neuronal damage in the hippocampus.
Clozapine inhibits development and expression of nicotine-induced locomotor sensitization in rats
(Wiley, 2009-01) Kayır, Hakan; Yıldırım, Murat; Uzbay, Tayfun; Göktalay, Gökhan; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji ve Klinik Farmakoloji Anabilim Dalı.; AAH-1448-2021; 6508023759
It has been shown that clozapine, the prototype of atypical antipsychotics, significantly reduces daily cigarette use and alcohol consumption in schizophrenic patients. However, our knowledge about the effect of clozapine on nicotine abuse is limited. Aim of this study was to determine whether clozapine would inhibit the development and expression of nicotine-induced locomotor sensitization in rats. To investigate the effect of clozapine on the development of nicotine-induced locomotor sensitization, rats were pretreated with clozapine (2.5-10 mg/kg) 30 min before the nicotine (0.5 mg/kg), and locomotor activity was recorded for 15 min. This procedure was repeated every day for eight sessions. After a 3-day drug-free period, rats were challenged with nicotine (0.5 mg/kg). To reveal effect of clozapine on the expression of nicotine-induced locomotor sensitization, rats were injected with nicotine for eight sessions. After a 3-day drug-free period, rats were pretreated with clozapine (2.5-10 mg/kg) or vehicle 30 min before the nicotine (0.5 mg/kg) challenge injection. Repeated administration or nicotine generated robust locomotor sensitization in rats. Clozapine pretreatment (2.5-10 mg/kg) blocked the development and the expression of nicotine-induced locomotor sensitization in rats. Our results suggest that atypical antipsychotic clozapine can prevent the effects of nicotine in an animal model of dependence, which represents early adaptations in initiation and continuation of addictive behavior.
Social interaction of rats is related with baseline prepulse inhibition level
(Elsevier, 2014-09-01) Kayır, Hakan; Ulusoy, Kemal Gökhan; Uzbay, Tayfun; Göktalay, Gökhan; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Farmakoloji Anabilim Dalı.; AAH-1448-2021; 6508023759
The symptoms of schizophrenia are evaluated in three general categories: positive, negative and cognitive symptoms. Disruption of prepulse inhibition (PPI) of the acoustic startle reflex is commonly used to model positive and cognitive symptoms in experimental animals. On the other hand, deficient social interaction (SI) is a common model of negative symptoms. Here we tested whether PPI provides information about negative symptoms by using a SI test. Baseline PPI and its relation with anxiety-like behavior were also examined with elevated plus maze (EPM) test. In the first experiment, baseline PPI levels of 30 Wistar rats were measured and animals with the highest 1/3 and the lowest 1/3 of PPI scores were respectively assigned in high-inhibitory (HI) and low-inhibitory (LI) groups. Subsequently, rats in the HI and LI groups were paired with animals from the same group and tested for SI. In the second experiment, another batch of animals was assigned to HI and LI groups and they were investigated in the EPM test. The results demonstrate a significant difference between the PPI values of HI and LI groups. Both the SI time and the moving distance of LI rats were significantly lower, and the average distance between rat pairs was significantly longer than HI rats. In the EPM test LI and HI rats showed similar levels of anxiety-like behaviors, however our results imply that performance of the rats in the SI test is related to baseline PPI levels. Thus PPI test can provide predictive information about the outcome of animal models for negative symptoms in rats. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
Stimulus properties of venlafaxine in a conditioned taste aversion procedure
(Elsevier, 2008-10-31) Kayır, Hakan; Alıcı, Tevfik; Yıldırım, Murat; Ulusoy, Kemal Gökhan; Ceyhan, Mert; Çelik, Turgay; Uzbay, Tayfun; Göktalay, Gökhan; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji ve Klinik Farmakoloji Anabilim Dalı.; 0000-0001-6261-4233; AAH-1448-2021; 6508023759
Conditioned stimulus properties of venlafaxine are still unknown. In the present study, the discriminative stimulus properties of venlafaxine by using a conditioned taste aversion procedure were investigated. Swiss Webster mice were allowed to reach water from 2 pipettes for 20 min (09:00-11:30 h), plus 30 min (15:3016:00 h), daily. During the 4 days, the test drugs [fluoxetine, escitalopram, tianeptine, reboxetine, and N omega-nitro-L-arginine methyl ester(L-NAME)l were injected to mice at least 1 h after they had first water session. On day 5, they consumed glucose solution(5%w/v) and immediately injected with conditioning drug (venlafaxine 32 mg/kg). On day 8, mice were allowed to make a choice between water and glucose solution. The amount of glucose consumption as a percentage of total fluid intakes was calculated for each animal. Significant reduction in glucose choice was defined as conditioned taste aversion. Venlafaxine (32 mg/kg) induced a robust conditioned taste aversion in mice. Pre-exposure to tianeptine (2.5-10 mg/kg), fluoxetine (10 mg/kg), escitalopram (32 mg/kg), and reboxetine (5 mg/kg) substituted for venlafaxine by preventing the conditioned taste aversion induced by venlafaxine. L-NAME did not substitute for venlafaxine. Substitution of venlafaxine by fluoxetine, tianeptine, escitalopram, and reboxetine provides further evidence that both 5-HT and noradrenaline reuptake inhibition may play an important role in the stimulus effect of venlafaxine.
Valproik asitle indüklenmiş otizm spektrum bozukluğu sıçan modelinde doğumsal malformasyonlar
(Bursa Uludağ Üniversitesi, 2019-04-07) Uzbay, Tayfun; Öz, Pınar; Tunçak, Süeda; Gören, Bülent; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.
Otizm genetik ve çevresel bir etiolojiye sahip davranışsal, gelişimsel ve nörolojik semptomlarla görülen bir spektrum bozukluğudur. Prenatal dönemde valproik asit (VPA) maruziyeti sıçanlarda otizm benzeri semptomlara neden olur ve insanlarda da benzer etkiler göstermesi nedeniyle tercih edilen bir modeldir. Çalışmamızda 8 gebe Wistar albino sıçan kullanılmıştır. E12,5’de 5 anne sıçan 400 mg/kg/ml VPA’e, 3 anne sıçan ise aynı volümde serum fizyolojiğe maruz kalmıştır. Doğan 79 yavru (nVPA: 48, nctrl: 31) P22’de muayene edilmiştir. VPA’e maruz kalmış 48 yavrudan 30’u malformasyonlara sahipken, kontrol grubu yavrularda herhangi bir malformasyon görülmemiştir. Görülen malformasyonlar; 48 hayvanın 22’sinde (%45,83) kuyruk kırılması, 8’inde (%16,66) ekstra parmak benzeri pati deformasyonu, ve 1’inde (%2,08) ayak duruş deformitesi ve motor kuvvet kaybı şeklindedir. Cinsiyetler arasında malformasyon dağılımı bakımından bir fark yoktur. Kuyruk kırılmaları lokasyon ve ciddiyet bakımından karakterize edilmiştir. Kuyruğun proksimal kısmında orta ve distal kısma göre daha fazla kırılma görülmüştür. Sonuçlarımız fiziksel malformasyonlar şeklinde karşımıza çıkan VPA’in teratojenik etkilerini doğrular niteliktedir. Malformasyonlar ve davranışsal semptomlar arasındaki muhtemel ilişki için ek çalışmalar gerekmektedir. Bulgularımız VPA maruziyetiyle oluşturulan otizm modelinin semptomatik geçerliliğini artırmakta ve modelin semptomatik spektrumunu genişletmektedir.
Varenicline disrupts prepulse inhibition only in high-inhibitory rats
(Pergamon-Elsevier Science Ltd, 2014-03-04) Göktalay, Tuğba; Coşkun, Ayşın Şakar; Yorgancıoğlu, Arzu A.; Kayır, Hakan; Uzbay, Tayfun; Buyükuysal, Sema; Uslu, Gülşah; Göktalay, Gökhan; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Farmakoloji Anabilim Dalı.; AAH-1448-2021; 57194751676; 56084705600; 6508023759
Varenicline, a widely used smoking cessation drug, has partial agonistic activity at alpha 4 beta 2 nicotinic receptors, and full agonistic activity at alpha 7 nicotinic receptors. Thus it may interact with cognitive processes and may alleviate some of the cognitive disturbances observed in psychotic illnesses such as schizophrenia. We aimed to test the effects of varenicline on sensorimotor gating functioning, which is crucial for normal cognitive processes, especially for the integration of sensory and cognitive information processing and the execution of appropriate motor responses. Prepulse inhibition (PPI) of the acoustic startle reflex was used to test the sensorimotor gating functioning. First, the effects of varenicline and nicotine on rats having high or low baseline PPI levels were evaluated; then, varenicline was applied prior to apomorphine (0.5 mg/kg), and MK-801 (0.15 mg/kg), which are used as comparative models of PPI disruption. Varenicline (0.5-3 mg/kg) did not change PPI when given alone in naive animals. When rats were selected according to their baseline PPI values, varenicline (1 mg/kg) significantly decreased PPI in high-inhibitory (HI) but not in low inhibitory (LI) rats. Nicotine (1 mg/kg; tartrate salt) produced a similar activity in LI and HI groups. In combination experiments, varenicline did not reverse either apomorphine or the MK-801-induced disruption of PPI. These results demonstrate that the effects of both varenicline and nicotine on sensorimotor gating are influenced by the baseline PPI levels. Moreover, varenicline has no effect on apomorphine or the MK-801-induced disruption of PPI. (C) 2014 Elsevier Inc. All rights reserved.