Physiology and Pharmacology
Year:2006 | Volume:10 | Issue:2|Papers Count:13

Introduction: It is believed that Locus Coeruleus (LC) influences the sensory information processing. However, its role in cortical surround inhibitory mechanism is not understood. In this experiment, using controlled mechanical displacement of whiskers; we investigated the effect of phasic electrical stimulation of LC on response of layer V barrel cortical neurons in anesthetized rat.Methods: LC was stimulated 0, 50, 100, 200 and 400ms before principal or adjacent whiskers deflection. For assessing the effect of LC stimulation on inhibitory receptive field of the barrel neurons, adjacent whisker was also deflected 20ms before principal whisker deflection, and LC stimulation was applied 0-400 ms before principal whisker displacement.Results: We found that LC stimulation increased the response magnitude of layer V neurons to principal whisker deflection (significance level (p<0.05) at 50-400 ms intervals). This increase in response magnitude was observed to adjacent whisker deflection too (significant (p<0.01) at 100 ms interval). The response latency of neurons was decreased when LC was stimulated 400ms before principal whisker deflection (p<0.01). LC stimulation did not affect the neuronal response latency to adjacent whisker displacement or spontaneous activity of neurons. Inhibitory effect of adjacent whisker deflection on neuronal response magnitude was increased by LC stimulation when tested when combined whisker displacement.Conclusion: These findings suggest that LC by modulating the neuronal responses enhances the neuronal responsiveness to sensory stimuli and increases their surround inhibition in cortex.

Introduction: Dill (Anethum graveolens), a herb from from Umbelliferae, is used traditionally to treat convulsion and increasing milk production. Its antimicrobial, antihyperlipidaemic, anti-hypercholesterolemia effects and gastric acid secretion reducing effect have been reported. The spasmolytic effect of dill fruit on rat uterus has also been shown recently. The aim of present study was to investigate the effects of dill fruit hydroalcoholic (DFHE) extract on rat ileum contractions induced by KCl (60mM), acetylcholine (1mM) and BaCl2 (4mM). Methods: Dill fruit was extracted by 70 % alcohol for 72 h and macerated method was used. Male Wistar rats were killed by a blow to head and pieces of end portion of ileum (2 cm) were dissected out and washed with cooled oxygenated Tyrode's solution. Ileum was mounted in an isolated organ bath containing Tyrode solution (37 °c) bubbled by air. An isotonic transducer was used to record contractile responses under 0.5g initial tension.Results: The cumulative concentrations of DFHE (0.5, 1, 2, and 4 mg/ml) relaxed the KCl-, acetylcholine and BaCl2-induced contractions dose-dependently (n=8, p<0.0001). This spasmolytic effect of extract (at all concentrations) on BaCl2-induced contraction was more potent than on the acetylcholine-induced contraction, In addition, the antispasmodic effect of DFHE was reversible after washing the organ bath. The inhibitory effect of extract (1mg/ml) on contraction induced by KCl was unaffected neither by phentolamine (1 mM, for 30 min), propranolol (1 mM, for 30 min) nor naloxone (1 mM, for 30 min). L-NAME (100 mM, for 20 min) was also ineffective in this respect. In Ca2+-free,rich K+(120 mM) Tyrode solution, cumulative adding of calcium (0.225. 0.45, 0.9, 1.8 and 3.6 mM), increased contractions dose dependently (p<0.0001). DFHE (1 mg/ml) shifted this dose-response curve to the right (p<0.0001).Conclusion: These results suggest that the relaxatory effect of DFHE on ileum contractions is due to the blockade of voltage dependent calcium channels. In addition, the a- and b-adrenoceptors, opioid receptors and NO production are not involved in this inhibitory effect of DFHE.

Introduction: Ultra low dose (ULD) morphine induces hyperalgesia which is mediated by excitatory Gscoupled opioid receptors. This study was designed to investigate the development of tolerance to hyperalgesic effect of morphine. Also we attempt to seek possible similarity, in view of Gs proteins, between hyperalgesic effect of ULD and hyperalgesic effect after tolerance to HD.Method: Male Wistar rats weighing 180-220 g were used. All injections were given intra peritoneally. For tolerance induction animals received ULD or HD for 5 days and at the 6th day tail flick test was performed before and 30 min after morphine administration. Effect of pretreatment with ULD on analgesic tolerance was assessed by injection of ULD before HD in 5 consecutive days then TF record was done after HD injection on 6thday. Time interval between injections was 15 minutes. Cross tolerance assay was measured by recording the response to a specified dose in 6th day after 5 days treatment with another dose. Oseltamivir, as a GMl ganglioside inhibitor, was used for inhibition of Gs signaling. Results: Our results showed that: 1) tolerance was established after chronic injection of ultra low dose (ULD) of morphine. 2) Pre-treatment by ULD reduced tolerance to therapeutic dose of morphine. 3) Cross tolerance to analgesia was observed after chronic administration of ULD. 4) Combination therapy with oseltamivir blocked hyperalgesia; reduced analgesic tolerance and attenuated the development of tolerance to hyperalgesic effect of morphine.Conclusion: The results showed the partially common mechanism for development of tolerance to hyperalgesic and analgesic effect of morphine. Signaling through Gs proteins seems to be a common pathway.

Introduction: It has been reported that oral morphine dependency facilitated formation of spatial learning and memory. In the present study the role of NMDA receptors located in hippocampal CAI area of morphine dependent rats was studied.Methods: Male rats were divided into 4 groups. Two cannulae were stereotaxically implanted bilaterally into the hippocampal CA1 area. After 5 days recovery, animals received morphine sulfate or sucrose for 30 consecutive days in drinking water. Morris water maze (MWM) studies were performed from day 26 to 30. In the above mentioned days, animals received bilateral intrahippocampal CA1 area injection of 3.7mg/0.5m D,L-AP5 (NMDA receptors antagonist) or 0.5ml saline, 30 min before daily experimentation. Spatial learning and memory parameters were subjected to the analysis of variance (ANOVA).Results: Morphine dependence potentiated spatial learning and memory parameters using MWM. D,L-AP5 could inhibit formation of spatial learning and memory in both control and dependent group.Conclusion: Activation of NMDA receptors located in hippocampal CA1 area is essential for potentiation of spatial learning and memory in morphine dependence rats.

Introduction: Embryonic Stem (ES) cells as pluripotent cells derived from the inner cell mass of blastula can differentiate to neural cells in vitro and this property is valuable in studies of neurogenesis and in the generation of donor cells for transplantation. In this regard, the propose of this research, was the study of the role of two important factors in the development of neural system, Fibroblast Growth Factor and Retinoic Acid were used in the study of mouse ESCs differentiation into neural cells.Methods: Royan BI ESCs were used in this experiment. The formation of embryoid bodies (EBs) within 2days was the key indication of the differentiation process and then the treatment was carried out under the influence of different factors for example retinoic acid and fibroblast growth factor-2 within 4days in cell culture media in 6 groups and finally the EBs were transferred on poly-L-lysine coated dishes within 5 days to promotes the differentiation.Results: The Studying of b-tubulin III, as a marker of neural cells, in neural cells derived from the ESCs used immunocytochemistry method, and the results obtained from statistical analysis of the percentage of neural differentiate9 colonies, revealed that, retinoic acid is a strong inducer factor which caused the differentiation of ESCs into neural cells and under the influence of combination of fibroblast growth factor and retinoic acid, ESCs differentiated to the neural cells with longer and thicker outgrowth.Conclusion: This experiment showed that under the influence of fibroblast growth factor-2 and retinoic acid there is a possibility to generate an efficient and large numbers of neurons with longer and thicker outgrowth like motor neurons of spinal cord of posterior area which an suitable for transplantation in damaged spinal cord.

Introduction: Several investigations have indicated that dopamine D2 receptors could influence morphine reward. The influence of olanzapine (a D2 dopamine receptor antagonist) on the morphine-induced conditioned place preference (CPP) in male and female mice was investigated in the present study.Methods: The effects of olanzapine on the acquisition and expression of morphine CPP in male and female N-MRI mice (W: 20-25 g) were investigated in the present study.Resulted: Subcutaneous (s.c.) injection of morphine (1-10 mg/kg, three drug sessions) induced place preference both in male and female mice. Intraperitoneal (i.p.) administration of olanzapine (0.5-5 mg/kg) induced place aversion (CPA) in female mice but not in male mice. Administration of olanzapine (1, 2.5, 5 mg/kg, Lp.) reduced both the acquisition and expression of morphine-induced CPP in male and female mice. However, olanzapine (5 mg/kg, Lp.) caused more than 80% mortality in female but not male mice. The effects of olanzapine were reversed by L-arginine (20 mg/kg, i.p.) pre-administration.Conclusion: We conclude that olanzapine reduced morphine effects via different mechanism/s.

Introduction: Origanum vulgare a rich source of natural phenolic antioxidants and has potential to be a source of nutritional ingredients for functional food. Herbs such as Origanum have long been used in food preservation and in traditional medicine in the treatment of common ailments and have potential for positive modulation of oxidation-linked diseases such as diabetes. Here we investigated the effect of aqueous extract of Origanum (leaves, stems and flowers) on spatial learning.Methods: After scientific identification, the leaves were used for extraction. 35 adult NMRI male rats weighing 250-350 gr were utilized in 5 groups. Control group (no injection), the second group (saline injected), the extracts with different doses (150, 300, 450) mg/kg were injected intraperitoneally to experimental animals. All animals were trained for a spatial learning task using T-maze and were then trained subsequently daily based on standard method.Results: Statistic analysis ANOVA showed that Origanum aqueous extract significantly decreased the number of learning and error in simple and reverse learning (p<0.05) and it had no significant effect on delay time in both type of learning.Conclusion: It can be concluded that the effect of Origanum extract on learning can be due to its antioxidant and presence of anti acetylcholine estrase compounds such as ursolic acid.

Introduction: There are different applications for cooling in rehabilitation and there is also a controversy in results of applying ice on limb and its effects on motomeurons excitability.Methods: This study was done to determine the effect of applying controlled cooling (rubbing cold ointment with 3°C temperature) on the spinal skin (around T11, place of S11 root nerve) on the excitability of soleus motomeurons in ten healthy, non-athletic men. Each volunteer was tested in two [control (vazeline ointment with environment temperature) and examination (cold vazeline)] separate sessions. We used soleus H-reflex and Mh-wave recruitment curve parameters for evaluation. Stimulation current was a square pulse with 700 microsecond duration and 0.2 Hz frequency. H-reflex was recorded with 9 different amplitudes.Results: Fit L3 slope, fit L5 slope and peak to peak amplitude of H-reflex decreased immediately and 30 minutes after the application of cold ointment.Conclusion: Cold by stimulating the thermoreceptors and reducing the firing rate of surface mechanoreceptors can decrease the excitability of motoneurons and this effect may be long lasting.

Introduction: Estrogen is one of the female sexhormones that in addition to its reproductive role, has favorable effects on the metabolism of blood lipids and lipoproteins and by this way decreases the coronary heart disease. On the other hand, phytoestrogens are phytochemical substances that have effects like estrogens. Isoflavones, which the most important of them is genistein, are the most common form of phytoestrogens. In this research, the effects of one phytoestrogenic compounds named genistein and one estrogenic compound named ethinyl estradiol were compaired. The purpose of this comparison was to study of replacement possibility of phytoestrogens in ERT period for elimination of side effects of estrogenic compound.Methods: First the rats were fed for 2 months with high cholestrol diet (2% cholestrol, 0/5% cholic acid). After the first blood test ensured the hypercholestrolemic condition, the rats were treated for 2 months with ethinyl estradiol and genistein besides of high cholestrol diet. After the end of the second period and serum preparation from the blood samples disignated total cholestrol, triglyceride, HDL, LDL and VDL were measured and the. Results were statistically analyzed.Results: According to the obtained results of the first period of experiment, the usage of high cholestrol diet caused meaningful increase in total cholestrol and LDL as it made rats hypercholestrolemic. According to the results of second period of experiment, the usage of ethinyl estradiol reduced the level of serum total cholesterol and LDL of hypercholestrolemic rats, that was because of the effect of estrogen on increase of LDL catabolism. Whereas, it did not produce meaningful changes in triglyceride, HDL and VDL. Usage of genistein in isolated form had no benefical effect on blood lipids and lipoproteins, Because hypocholestrolemic property of isoflavone depends on matrix that is beside it.

Introduction Numerous studies have demonstrated the presence of potassium selective channels in membranes of internal organelles. These channels are essential to a large variety of cellular processes including intracellular Ca2+ signaling, protein recycling, charge neutralization and cell protection. In contrast to the sarcoplasmicreticulum where potassium channels have been clearly identified, there is little evidence for K+ selective cannels in RER of hepatocytes. The aim of this study is to find an evidence for presence of potassium channel in endoplasmic reticulum and considering the pharmacological and biophysical properties of this channel. Methods: Hepatocytes RER vesicles were isolatedby homogenizing rat liver followed by several centrifuging steps and then incorporated into the bilayer lipid membrane (BLM). The BLM was formed by painting phosphatidylcholine across the 350 mm aperture seperating two chambers (cis chamber containing 200 mMKCl and trans chamber containing 50 mM KCI). Single channel recordings were used to indicate the presence of K+ channels.Results: Single channel recordings revealed the existence of a cation selective channel with high permeability to K+ and 599 pS conductance. The current-voltage relation was linear. The open probability was strongly voltage dependent, showing higher values at positive voltages and lower at negative voltages. A sub conductance state about 60 % of fully open state was observed at all voltages. The cationic channel showed an inhibition by 4- aminnopyridine (non specific K+ channel blocker) Conclusions: In this study we have established an evidence for existence of large conductance K+ channel in the hepatocyte ER vesicles.