Fazilet Aksu

Dual effects of nitric oxide in the mouse forced swimming test: possible contribution of nitric oxide-mediated serotonin release and potassium channel modulation.

Recent findings have indicated that nitric oxide (NO) may change the duration of immobility biphasically in the forced swimming test, which is a useful experimental model for screening antidepressant-like activity in rodents. In the present study, we have investigated the role of serotonin and of potassium (K(+)) channels in the dual effects of NO in the mouse forced swimming test (MFST). For this purpose, we tested the effects of l-arginine, an NO precursor, the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME), and of K(+)-channel blockers tetraethylammonium (TEA) and 3,4-diaminopyridine (3,4-DAP). In addition, we used sertraline as a serotonin reuptake inhibitor and cyproheptadine as a serotonin antagonist. l-Arginine increased the duration of immobility in the MFST in low doses (25 mg/kg ip) but decreased it in higher doses (500 and 1000 mg/kg ip). Low doses of l-NAME (50 and 75 microg icv) decreased while higher dose of this drug (150 microg icv) increased the immobility time. TEA (5 microg icv) and 3,4-DAP (0.05 microg icv) significantly reduced the time, whereas K(+) channel opener pinacidil increased the duration of immobility. l-Arginine (100 mg/kg ip) significantly antagonised the effects of l-NAME (50 microg), 3,4-DAP and TEA. Higher dose of l-arginine (500 mg/kg ip) significantly potentiated the effects of 3,4-DAP and TEA, but reduced the effect of pinacidil. Low doses of l-arginine antagonized, but higher doses of l-arginine potentiated the antidepressant-like effect of sertraline. Sertraline potentiated the effects of 3,4-DAP and TEA, but reversed the effect of pinacidil. Cyproheptadine reduced the anti-immobility effect of l-arginine and 3,4-DAP. At the highest effective doses, drugs did not impair the motor functions. These data support the hypothesis that NO effects may involve the release of serotonin and/or modulation of K(+) channels.

Antidepressant-like effect of tramadol in the unpredictable chronic mild stress procedure: possible involvement of the noradrenergic system.

Tramadol, which inhibits the reuptake of noradrenaline and serotonin, is effective in animal models of depression. Its antidepressant-like effects may be mediated mainly by the noradrenergic system. This study investigated the role of the noradrenergic system in the antidepressant-like effects of tramadol and desipramine in the unpredictable chronic mild stress model. We assessed the involvement of &bgr;-adrenoreceptors, particularly &bgr;2-receptors in the activity of these drugs. In addition, we measured the level of noradrenaline and its metabolite 3-methoxy-4-hydroxy-phenylglycol (MHPG) in the locus coeruleus, hypothalamus, hippocampus and cerebellum in stressed mice. Unpredictable chronic mild stress induced a degradation of coat state and decreased grooming behaviour in the splash test, which was reversed by the chronic administration of tramadol (20 mg/kg) and desipramine (10 mg/kg). The nonselective &bgr;-adrenoreceptor antagonist propranolol (5 mg/kg, intraperitoneally) and the selective &bgr;2-receptor antagonist ICI 118,551 (2 mg/kg, intraperitoneally) reversed the antidepressant-like effects of tramadol and desipramine. Moreover, chronic tramadol and desipramine treatment increased the level of noradrenaline (NA) and MHPG in the locus coeruleus but not in the cerebellum, whereas only MHPG level was increased in the hypothalamus. Tramadol, however, increased the levels of MHPG and NA in the hippocampus, whereas desipramine only increased NA level. These data support the view that the noradrenergic system plays an important role in the antidepressant-like action of tramadol.

Involvement of potassium channels and nitric oxide in tramadol antinociception

It has been considered that tramadol, a centrally acting analgesic, shows its effect via opiatergic, noradrenergic, and serotonergic systems. It has a low affinity for opioid receptors, and its effect can be partly blocked by naloxone. Since the noradrenergic and serotonergic mechanisms are still unknown, other systems which are associated with pain and analgesia may have a role on the antinociceptive effect of tramadol. The aim of this study was to evaluate the effects of K+ channels and nitrergic systems on the antinociceptive action of tramadol. The antinociceptive effects of tramadol were determined in mice by the hot plate test. To examine the effects of K+ channels and the nitrergic system nonspecific voltage-dependent K+ channel blockers 4-aminopyridine (4-AP) and tetraethylammonium (TEA), nitric oxide (NO) precursor L-arginine, and the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) were used. Our results indicated that 4-AP, TEA, and L-arginine reduced the antinociceptive effect of tramadol. However, L-NAME augmented the antinociceptive effect of tramadol. The reduction of the effects of tramadol by L-arginine was reversed by L-NAME. The results of our study suggest that nonspecific voltage-dependent K+ channels and nitrergic system have a role on the antinociceptive effect of tramadol in mice hot plate test.

The effects of some K+ channel blockers on scopolamine- or electroconvulsive shock-induced amnesia in mice

The effects of three K(+) channel blockers, 4-aminopyridine, 3, 4-diaminopyridine and apamin, on scopolamine- or electroconvulsive shock-induced amnesia were investigated in mice by using a one-trial step-down passive avoidance system. Scopolamine and electroconvulsive shock reduced the retention latency of passive avoidance, which indicated the amnestic effect of these treatments. 4-Aminopyridine, 3,4-diaminopyridine and apamin injected immediately after the acquisition trial, reversed the amnestic effect of scopolamine or electroconvulsive shock in a dose-dependent manner. None of the drugs or electroconvulsive shock treatment affected the rotarod or activity cage performance of the mice. These results indicate that K(+) channel blockers may improve cognitive deficits when memory is impaired by a drug or any other manipulation.

Influence of sex on the interaction between dizocilpine (MK-801) pretreatment and acute cold-restraint stress in epilepsy susceptibility in an animal study

BACKGROUND Stress is a part of our daily life, inducing neurochemical and neurophysiological changes in the central nervous system. OBJECTIVE The present study was designed to investigate the importance of sex differences in the interaction between dizocilpine (MK-801) pretreatment and acute cold-restraint stress (CRS) in pentylenetetrazole (PTZ)-induced seizures in Swiss albino mice. METHODS A CRS protocol was applied to mice to investigate the interaction between MK-801 pretreatment (30 min before CRS) and stress (followed by PTZ injection) in epilepsy susceptibility. For this purpose, 6 groups were designated: (1) PTZ control group (received only PTZ); (2) stress group (received stress and PTZ); (3) saline group (received saline and PTZ); (4) MK-801 group (received MK-801 and PTZ); (5) saline + stress group (received saline, stress, and PTZ); and (6) MK-801 + stress group (received MK-801, stress, and PTZ). RESULTS Pretreatment with MK-801 (0.125, 0.25, 0.50 mg/kg) significantly potentiated the protective effect of stress in PTZ-induced (65 mg/kg) seizures in both sexes by prolonging the onset of myoclonic jerks and clonic convulsions. Male mice had a significantly greater delay in the onset of myoclonic jerks (males, 66.7-295.5 sec; females, 54.0-247.5 sec; P < 0.05) and clonic convulsions (males, 123.5-789.8 sec; females, 94.5-757.2 sec; P < 0.05) compared with female mice in all groups (ie, PTZ control, stress, saline, MK-801, saline + stress, and MK-801 + stress groups). CONCLUSION The findings of this study in mice suggest the involvement of sex hormones in the interaction between MK-801 pretreatment and acute CRS in PTZ-induced seizures.

The effects of piracetam on morphine-induced amnesia and analgesia: The possible contribution of central opiatergic mechanisms on the antiamnestic effect of piracetam

The involvement of opiatergic mechanisms on the antiamnestic effects of piracetam was investigated in mice. First, the effects of piracetam and naloxone on the amnesia induced by scopolamine, electroconvulsive shock and morphine were evaluated by using elevated plus maze apparatus. Second, the effects of electroconvulsive shock and piracetam on the antinociceptive action of morphine were tested by means of radiant heat tail-flick experiment. Piracetam and naloxone reversed the drug- or electrically-induced amnestic effects. On the other hand, electroconvulsive shock treatment enhanced the antinociceptive effect of morphine while piracetam decreased the same activity. These results suggest an important role of the opiatergic system on the learning and memory process as well as on the antiamnestic effect of piracetam.

Synthesis of curcumin complexes with iron(III) and manganese(II), and effects of curcumin–iron(III) on Alzheimer's disease

Plants provide a wealth of bioactive compounds which aid in exerting a substantial strategy for the treatment of neurological disorders such as Alzheimers disease and dementia. Here, the metal complexes of the curcumin ligand were synthesized with Mn(II) and Fe(III) salts, and characterized by spectroscopic and analytical methods such as elemental analysis, magnetic susceptibility, FT-IR, AAS, TG and argentometry. Magnetic susceptibility data showed that complexes with 1 : 2 (metal : ligand) mole ratio had octahedral geometry. In vivo studies of the synthesized metal complexes had been carried out on Swiss albino male mice, to study their ability for reducing the accumulation of beta amyloid 25–35 protein which causes Alzheimers disease. Memory experiments were performed with the plus maze test at behavioural pharmacology laboratory. LP rates of Aβ25–35/curcumin and Aβ25–35/Fe(III) complex groups were 80.79%, 88.21% and 75.35%, 81.71%, respectively. Consequently, the synthesized curcumin iron complex strengthened the memory. It was more effective than curcumin, when their latent period (LP) values were compared.