Semil Selcen Gocmez

Beneficial effects of resveratrol on scopolamine but not mecamylamine induced memory impairment in the passive avoidance and Morris water maze tests in rats.

Resveratrol (3,5,4-trihydroxy-trans-stilbene), which is found in grapes and red wine has been shown to protect neuronal cells with its antioxidant activity, improve memory function in dementia and reverse acetylcholine esterase (AChE) activity. The aim of this study was to investigate the effect of resveratrol on emotional and spatial memory in naive rats, as well as on scopolamine- and mecamylamine-induced memory impairment in the passive avoidance and Morris water maze (MWM) tests. Resveratrol (12.5, 25 and 50 mg/kg), scopolamine (0.6 mg/kg) and mecamylamine (10mg/kg) were administered to male Wistar rats. In the passive avoidance test, there was no significant difference in the first day latency between all groups, whereas scopolamine and mecamylamine significantly shortened the second day latency compared to the control group. Resveratrol reversed the effect of scopolamine at all doses used, but it had no effect on mecamylamine-induced memory impairment in the passive avoidance test. Both scopolamine and mecamylamine significantly decreased the time spent in the escape platform quadrant during the probe trial of the MWM test compared to the control group. Resveratrol reversed the effect of scopolamine at all doses, but did not change the effect of mecamylamine in the MWM test. There were no significant differences in the locomotor activities of any of the groups. In conclusion, we suggested that resveratrol had improving effects on learning and memory by acting on muscarinic cholinergic receptors and at least in part, may reverse AChE activity.

Agmatine, a metabolite of L-arginine, reverses scopolamine-induced learning and memory impairment in rats.

Agmatine (l-amino-4-guanidino-butane), a metabolite of L-arginine through the action of arginine decarboxylase, is a novel neurotransmitter. In the present study, effects of agmatine on cognitive functions have been evaluated by using one trial step-down passive avoidance and three panel runway task. Agmatine (20, 40, 80 mg/kg i.p.) was administered either in the presence or absence of a cholinergic antagonist, scopolamine (1 mg/kg i.p.). Scopolamine significantly impaired learning and memory in both passive avoidance and three panel runway test. Agmatine did not affect emotional learning, working and reference memory but significantly improved scopolamine-induced impairment of learning and memory in a dose dependent manner. Our results indicate that agmatine, as an endogenous substance, may have an important role in modulation of learning and memory functions.

Chronic administration of fluoxetine impairs neurogenic and endothelium-dependent relaxation of the rabbit corpus cavernosum smooth muscle

Antidepressants, including selective serotonin reuptake inhibitors (SSRIs), cause erectile dysfunction; however, the mechanism by which they cause erectile function is unclear. We investigated the reactivity of the corpus cavernosum after chronic fluoxetine treatment in rabbits. Twelve rabbits were randomly divided into two groups: control (n=6) or 20mg/kg/day of fluoxetine delivered i.p. (n=6). The reactivity of the corpus cavernosum tissue from the fluoxetine-treated and control groups was studied in organ chambers after 21 days of fluoxetine injection. In the fluoxetine-treated group, endothelium-dependent relaxation of the corpus cavernosum in response to acetylcholine was significantly decreased compared to the control group. However, the sensitivity (i.e., pD(2)) of the fluoxetine-treated cavernosal tissue strips to acetylcholine was not changed with respect to controls. Electrical field stimulation (EFS)-induced neurogenic relaxation was also significantly reduced in the fluoxetine-treated group. Relaxation in response to the nitric oxide (NO) donor sodium nitroprusside was similar between the cavernosal tissues from the two groups. There was also no change in agonist potency between the two groups. Additionally, chronic fluoxetine treatment had no effect on KCl-induced contractile responses. When tissue contraction was produced with phenylephrine to study relaxation in response to various stimuli, the tension induced was similar between the fluoxetine-treated and control groups. This study suggests that chronic fluoxetine treatment causes significant functional changes to the penile erectile tissue of rabbits, and these changes may contribute to the development of impotence.

Selective and nonselective neuronal NOS inhibitors impair cognitive function in the three panel runway and passive avoidance tasks in rats

The aim of this study was to compare the effects of both neuronal NOS (nNOS) and inducible NOS (iNOS) inhibitor 2-iminobiotin, with the more selective nNOS inhibitor N(ω)-propyl-L-arginine (NPLA) and selective inducible NOS (iNOS) inhibitor aminoguanidine, on emotional learning, working memory and reference memory, by using three panel runway and passive avoidance paradigm in order to clarify the role of distinct isoforms of NOS in the regulation of learning and memory functions. NPLA and 2-iminobiotin significantly increased the number of errors and latency of working and reference memory performances of rats in three panel runway paradigm and impairs retention for the passive avoidance task. However, aminoguanidine did not affect cognitive functions in three panel runway and passive avoidance test. The effect of NPLA and 2-iminobiotin was reversed by pretreatment with a NOS substrate L-arginine. In conclusion, NPLA and 2-iminobiotin impaired cognitive functions in different kind of tasks used in this study and the effect of NPLA and 2-iminobiotin was found to be NO-dependent. Our results may confirm that nNOS plays the key role on emotional learning, working memory and reference memory in rats.

The effect of a selective neuronal nitric oxide synthase inhibitor 3-bromo 7-nitroindazole on spatial learning and memory in rats.

Since the discovery of nitric oxide (NO) as a neuronal messenger, its way to modulate learning and memory functions is subject of intense research. NO is an intercellular messenger in the central nervous system and is formed on demand through the conversion of L-arginine to L-citrulline via the enzyme nitric oxide synthase (NOS). Neuronal form of nitric oxide synthase may play an important role in a wide range of physiological and pathological conditions. Therefore the aim of this study was to investigate the effects of chronic 3-bromo 7-nitroindazole (3-Br 7-NI), specific neuronal nitric oxide synthase (nNOS) inhibitor, administration on spatial learning and memory performance in rats using the Morris water maze (MWM) paradigm. Male rats received either 3-Br 7-NI (20mg/kg/day) or saline via intraperitoneal injection for 5days. Daily administration of the specific neuronal nitric oxide synthase (nNOS) inhibitor, 3-Br 7-NI impaired the acquisition of the MWM task. 3-Br 7-NI also impaired the probe trial. The MWM training was associated with a significant increase in the brain-derived neurotrophic factor (BDNF) mRNA expression in the hippocampus. BDNF mRNA expression in the hippocampus did not change after 3-Br 7-NI treatment. L-arginine significantly reversed behavioural parameters, and the effect of 3-Br 7-NI was found to be NO-dependent. There were no differences in locomotor activity and blood pressure in 3-Br 7-NI treated rats. Our results may suggest that nNOS plays a key role in spatial memory formation in rats.

Chronic administration of imipramine but not agomelatine and moclobemide affects the nitrergic relaxation of rabbit corpus cavernosum smooth muscle.

Sexual dysfunction is a common and underestimated effect of antidepressants. However, the mechanism by which these drugs cause erectile dysfunction is unclear. We investigated the reactivity of the corpus cavernosum of rabbits that were treated with either chronic imipramine, which is a tricyclic agent; agomelatine, which is a melatonergic agonist and serotonin 5HT(2c) antagonist; or moclobemide, which is a reversible inhibitor of monoamine-oxidase A. Twenty rabbits were randomly divided into four groups: the control group (n=5), the imipramine-treated group (n=5), which received i.p. injections of 10 mg/kg/day of imipramine, the moclobemide-treated group (n=5), which received i.p. injections of 20 mg/kg/day of moclobemide, and the agomelatine-treated group (n=5), which was orally administered 10 mg/kg/day of agomelatine. The reactivities of corpus cavernosum tissue obtained from the antidepressant-treated and the control groups were studied in organ chambers after the animals were subjected to 21 days of drug administration. The acetylcholine-induced endothelium-dependent and the electrical field stimulation (EFS)-induced neurogenic relaxation of the corpus cavernosum of the imipramine-treated group was significantly decreased compared with the control group. However, neither the acetylcholine- nor EFS-induced relaxation was changed in the moclobemide- or agomelatine-treated groups. There were no change in the relaxant response to the nitric oxide (NO) donor sodium nitroprusside and contractile response to KCl between the groups. This study suggests that chronic imipramine treatment but not agomelatine and moclobemide treatments causes significant functional changes in the penile erectile tissue of rabbits and that these changes may contribute to the development of impotence.

Anti-inflammatory and ultrastructural effects of Turkish propolis in a rat model of endotoxin-induced uveitis.

INTRODUCTIONnExperimental animal models of acute uveitis, an inflammatory eye disease, can be established via endotoxin-induced inflammation. Propolis, a natural substance collected by honeybees from buds and tree exudates, has antioxidant, antibacterial, antiviral, and anti-inflammatory effects. We investigated the effects of propolis, obtained from the Sakarya province of Turkey, on endotoxin-induced uveitis using immunohistochemical, ultrastructural, and biochemical approaches.nnnMATERIAL AND METHODSnMale Wistar albino rats (n = 6/group) received intraperitoneal (ip) lipopolysaccharide (LPS) endotoxin (150 μg/kg) followed by aqueous extract of propolis (50 mg/kg ip) or vehicle; two additional groups received either saline (control) or propolis only. After 24 h, aqueous humor (AH) was collected from both eyes of each animal for analysis of tumor necrosis factor-α (TNF-α) and hypoxia-inducible factor-1α (HIF-1α). Right eyeballs were paraffin-embedded for immunohistochemical staining of nuclear factor κB (NF-κB)/p65 and left eyeballs were araldite-embedded for ultrastructural analysis.nnnRESULTSnTreatment of LPS-induced uveitis with propolis significantly reduced ciliary body NF-κB/p65 immunoreactivity and AH levels of HIF-1α and TNF-α. Ultrastructural analysis showed fewer vacuoles and reduced mitochondrial degeneration in the retinal pigment epithelium, as compared to the uveitis group. The intercellular spaces of the inner nuclear layer and outer limiting membrane were comparable with those of the control group; no polymorphonuclear cells or stasis was observed in intravascular or extravascular spaces.nnnCONCLUSIONSnThis is the first report demonstrating an anti-inflammatory effect of Turkish propolis in a rat model of LPS-induced acute uveitis, suggesting a therapeutic potential of propolis for the treatment of inflammatory ophthalmic diseases.

P.1.j.017 Protective effects of resveratrol in aging-induced cognitive impairment in rats

the control group (240±40%; p< 0.05). Comparisons made at 0−5min (induction of LTP) and 1 h post-tetanization (establishment of LTP) indicated that isolated males showed significantly greater enhancement, with consistently higher values in PSA than control group (410±68% v.s. 350±40%; p< 0.05 and 321±63% v.s. 255±22%; p< 0.05). EPSP-LTPs were measured as 132±7% (control rats: 146±5%; p< 0.05), and 102±11% (104±4%; p< 0.05) for induction and maintenance, respectively. These data are accordance with the studies in which demonstrated that social isolation of rats during neonatal period or postnatal days 21−42 enhances LTP in the dentate gyrus [2] and the ventral tegmental area [3].

Vasodilation Responses to Non-Selective α-Adrenergic Blockage of Coronary Bypass Grafts in Diabetic and Non-Diabetic Patients: In Vitro Study

BACKGROUNDnAdrenergic tonus is increased in atherosclerotic coronary arteries. In this study, we aimed to demonstrate in vitro effects of phentolamine, a reversible nonselective alpha (α) adrenergic blocker, on coronary artery bypass grafts (CABG) and compare its effects in diabetic and nondiabetic patients.nnnMETHODSnA total number of 30 patients (15 diabetic and 15 nondiabetic) who were assigned to elective CABG surgery were enrolled into the study. For both groups of patients, 16 internal mammarian artery (IMA) samples, 16 saphenous vein (SV) samples and 16 radial artery (RA) samples were collected and studied in the tissue bath system. The vasodilatation responses to increasing doses of phentolamine were recorded.nnnRESULTSnWhen grafts were compared in terms of amount of vasodilatation to phentolamine, IMA had the most prominent vasodilatation followed by RA and SV respectively. Although the vasodilatation responses in nondiabetic patients were numerically higher than diabetic patients, there was no statistically difference between the groups.nnnCONCLUSIONnPhentolamine, a nonselective α adrenergic blocker, is proven to have equal vasodilatory effects in diabetic and nondiabetic CABG grafts and can safely be used both intravenously and topically in the perioperative period.