Statins have cholesterol-independent effects including an increased vascular nitric oxide activity and are commonly used by patients with cardiovascular disease. Such patients frequently have cardiovascular diseases, which may be treated with cilostazol, a platelet aggregation inhibitor. This study was designed to investigate whether combined use of cilostazol would increase the inhibitory effect of statin on vascular smooth muscle and how maturation would affect these responses. Female Wistar rats, aged 3-4 months (young) and 14-15 months (adult), were sacrificed by cervical dislocation and the thoracic aorta was dissected and cut into 3- to 4-mm-long rings. The rings were mounted under a resting tension of 1 g in a 20-ml organ bath filled with Krebs-Henseleit solution. Rings were precontracted with phenylephrine (10 M), and the presence of endothelium was confirmed with acetylcholine (10 M). Then, the concentration-response curves were obtained for atorvastatin alone (10 to 3 × 10 M; control) and in the presence of cilostazol (10 M) in young and adult rat aortas. This experimental protocol was also carried out in aorta rings, which had been pretreated with N-nitro-l-arginine methyl ester (l-NAME, 10 M). Atorvastatin induced concentration-dependent relaxations in young and adult rat thoracic aorta rings precontracted with phenylephrine. The pIC value of atorvastatin was significantly decreased in adult rat aortas. In addition, pretreatment of aortas with cilostazol enhanced the potency of atorvastatin in both young and adult aortas. Incubation with l-NAME did not completely eliminate the relaxations to atorvastatin in the presence of cilostazol. These results suggest that combined application of cilostazol with atorvastatin was significantly more potent than atorvastatin alone. Combined drug therapy may be efficacious in delaying the occurrence of cardiovascular events.

There are several reports on unfavourable effects of metabolic cage housing on animal welfare mainly due to the characteristic structures of these cages such as single housing and grid flooring. This study was aimed to compare the effects of long-term metabolic cage housing and conventional housing (normal grouped housing in standard cages) on the anxiety/depression-like behaviours in male rats. Anxiety/depression-related behaviours were evaluated by use of forced swimming test and open field test. Swimming and climbing were significantly lower and immobility duration higher in the metabolic cage group. In the open field test, total distance, mean velocity, time spent in the central area, zone transition, grooming, and rearing scores were significantly lower in the metabolic cage. Moreover, serum corticosterone level was higher in the metabolic cage group. The results of the study indicate that long-term metabolic cage housing may cause an increase in the anxiety- and depression-related behaviours in male rats.

Background/aim Kisspeptin is a neuropeptide with a primary role on the onset of puberty and has beneficial effects on ischemia/reperfusion (I/R) injury. In this study, we aimed to investigate the effect of kisspeptin administration on striatal I/R injury in mice. Material and methods Forty adult C57/BL6 mice were randomly divided into four groups: Sham, Kisspeptin, I/R, and I/R + Kisspeptin groups. The groups were administered with either physiological saline (Sham and I/R groups) or kisspeptin (Kisspeptin and I/R + Kisspeptin groups) intraperitoneally 40 min before the operation. A microdialysis probe was placed in the right striatum according to stereotaxic coordinates. During the experimental period, artificial cerebrospinal fluid was passed through the micropump. Then, transient cerebral ischemia was established by compressing both common carotid arteries with an aneurysm clip for 15 min and animals were reperfused for 2 h. Throughout the process of microdialysis (before, during and after I/R period), samples were collected to measure dopamine (DA), noradrenaline (NA), and 3,4-dihydroxyphenylglycine (DHPG) at intervals of 20 min continuously. At the end of the reperfusion period, the animals were decapitated, striatum was dissected, half of the animals were used for oxidative stress analyses (reduced glutathione, glutathione S-transferase (GST), superoxide dismutase (SOD), malondialdehyde (MDA), and the other half were used for histopathology analyses. Results Number of glial cells was significantly increased in kisspeptin-administered groups. DA levels in ischemic animals were decreased by kisspeptin administration (p < 0.0001). NA levels were reduced in animals administered with kisspeptin without I/R injury (p < 0.05). DHPG levels reduced during the reperfusion period in ischemic animals (p < 0.05). Kisspeptin did not exhibit a significant antioxidant activity in the ischemic animals, while GST and SOD levels were reduced in the I/R + kisspeptin group compared to the kisspeptin group (p < 0.05). Conclusion Our results suggest that kisspeptin may be regulating the neurotransmitter release and metabolism, as well as inflammatory response in brain upon I/R injury.

Alzheimer's disease (AD) is accepted as a form of progressive and irreversible dementia. It is known that cholinergic systems are commonly affected in AD. Neurokinin 3 receptor (NK3R) is involved in learning and memory related processes. Activation of NK3R is known to facilitate the release of many neurotransmitters such as acetylcholine (Ach), dopamine (DA), noradrenaline (NA). Based on this information, hypothesis of the study that NK3R agonism can have positive effects on behavioral and learning parameters through cholinergic and catecholaminergic mechanisms. The aim of this study was to investigate the effects of NK3R agonist senktide on cognitive and neurobehavioral mechanisms in model of AD.50 adult male Wistar albino rats were obtained; Control, AD, Control+NK3R agonist, AD+NK3R agonist, AD+NK3R agonist+antagonist groups. AD model was established by administering Aβ1-42 intracerebroventricularly. Following NK3R agonist+antagonist injections, open field (OF) and Morris water maze (MWM) were applied for behavioral and learning parameters. Hippocampus and cortex tissues were extracted. Analysis of cholinergic mechanisms from these tissues were performed by ELISA method.Group-time effect was significant in OF (p<0.05). Distance moved parameter was significant between groups in MWM (p<0.05). There was a significant difference between groups in AChE and ChAT levels (p<0.05). DA concentrations of brainstem samples were significant (p<0.05). There was no significant difference in NA concentration (p>0.05). NK3R agonists were found to be effective in improving cognitive functions in rats with AD pathology. It has been observed that positive effects on learning and memory performances can be mediated by cholinergic mechanisms.

Abstract. Alterations of essential elements in the brain are associated with the pathophysiology of many neuropsychiatric disorders. It is known that chronic/overwhelming stress may cause some anxiety and/or depression. We aimed to investigate the effects of two different chronic immobilization stress protocols on anxiety-related behaviors and brain minerals. Adult male Wistar rats were divided into 3 groups as follows ( n = 10/group): control, immobilization stress-1 (45 minutes daily for 7-day) and immobilization stress-2 (45 minutes twice a day for 7-day). Stress-related behaviors were evaluated by open field test and forced swimming test. In the immobilization stress-1 and immobilization stress-2 groups, percentage of time spent in the central area (6.38 ± 0.41% and 6.28 ± 1.03% respectively, p < 0.05) and rearing frequency (2.75 ± 0.41 and 3.85 ± 0.46, p < 0.01 and p < 0.05, respectively) were lower, latency to center area (49.11 ± 5.87 s and 44.92 ± 8.04 s, p < 0.01 and p < 0.01, respectively), were higher than the control group (8.65 ± 0.49%, 5.37 ± 0.44 and 15.3 ± 3.32 s, respectively). In the immobilization stress-1 group, zinc (12.65 ± 0.1 ppm, p < 0.001), magnesium (170.4 ± 1.7 ppm, p < 0.005) and phosphate (2.76 ± 0.1 ppm, p < 0.05) levels were lower than the control group (13.87 ± 0.16 ppm, 179.31 ± 1.87 ppm and 3.11 ± 0.06 ppm, respectively). In the immobilization stress-2 group, magnesium (171.56 ± 1.87 ppm, p < 0.05), phosphate (2.44 ± 0.07 ppm, p < 0.001) levels were lower, and manganese (373.68 ± 5.76 ppb, p < 0.001) and copper (2.79 ± 0.15 ppm, p < 0.05) levels were higher than the control group (179.31 ± 1.87 ppm, 3.11 ± 0.06 ppm, 327.25 ± 8.35 ppb and 2.45 ± 0.05 ppm, respectively). Our results indicated that 7-day chronic immobilization stress increased anxiety-related behaviors in both stress groups. Zinc, magnesium, phosphate, copper and manganese levels were affected in the brain.