Physiology and Pharmacology
Year:2007 | Volume:11 | Issue:3|Papers Count:14

Introduction: Nimodipine, an L-type calcium channel blocker, can induce analgesia. However, it is not clear that this analgesic effect is at the level of spinal or supraspinal pain pathway. In addition, it has been reported that the analgesic effect of nifedipine, another L-type calcium channel blocker is related to the HPA axis, but there is no report indicating the role of this axis in the analgesic effect of nimodipine.Methods: Analgesia was measured by tail-flick (TF) test involving spinal reflexes and by hot-plate (HP) requiring an intact central nervous system. Assays were done before and 15, 30, 60 and 120 min after drug administration in the intact, sham operated and adrenalectomized rats. To identify the interaction between nimodipine and HPA axis, plasma corticosterone level was measured using the radioimmunoassay.Results: Nimodipine significantly decreased the plasma corticosterone level, and showed significant antinociception in both tests. Adrenalectomy potentiated the analgesic effect of nimodipine which was reversed by corticosterone replacement. Furthermore, nimodipine analgesic effect in ADX rats was more potent in HP test (compared to TF test).Nimodipine, at mentioned doses, did not alter animal's movement indices in activity monitoring test. Conclusion: Nimodipine involves both spinal and supraspinalsites to control thermal pain transmission in presence of adrenalgland. It seems that there is a mutual interaction between nimodipine and HPA axis, especially at supraspinal levels.

Introduction: It has been previously reported that oral morphine dependence facilitates formation of spatial learning and memory in rats. Therefore, in the current study the long lasting effects of morphine on above mentioned phenomena in with drawn animals were studied.Methods: In present study N-MRI male rats (250-350 g) received morphine sulfate (0.1- 0.4 mg/m!) (in dependent and withdrawal groups) or sucrose (in control group) in drinking water for 30 consecutive days. Morris water maze (MWM) studies were performed during morphine or sucrose application (in control and dependent animals), or after morphine elimination (in withdrawal groups). Spatial learning and memory parameters were recorded and subjected to the ANOVA.Results: Data showed better acquisition of spatial learning in dependent and withdrawal groups with respect to control animals.Conclusion: Oral morphine dependence has long lasting facilitator effect on acquisition of spatial learning in rats.

Introduction: Epilepsy is among the most common disorders of the central nervous system and there is not an absolute method for its treatment. It has been shown that each seizure has a depressing effect on the following seizure.Thus, finding the mechanisms responsible in this phenomenon can improve our knowledge toward new ways for epilepsy treatment. In this study, the role of adenosine AI receptors in post seizure depressing period was investigated in amygdale kindling model of epilepsy.Methods: Rats were kindled by daily electrical stimulation of amygdale. At first, different groups of kindled animals were stimulated at different times after the first stimulation and the percent of suppression of seizure parameters were calculated. Then, 8-cyclopenthyl-l, 3-dimethylxanthine (CPT), a selective adenosine AI receptor antagonist (50 and 200 mM) were intracerebroventriculady microinjected before the second stimulation and its effect on percent of suppression induced by the first stimulation was investigated.Results: In the second stimulation, applied at 10 and 30 min after the first stimulation, the seizure parameters were significantly reduced. CPT microinjection (50 and 200 mM) significantly decreased the percent of suppression of seizure parameters. This decrease was significant at 10 and 30 min after the first stimulation with compare to the groups received the drug solvent.Conclusion: Obtained results showed that endogenous adenosine has a role in post seizure depression period through Al receptors. As the blocking of AI receptors by CPT could not completely prevent this period, other factors may also play role in this suppression.

Introduction: Considering the important role of nucleus accumbens in drug reward, in the present study, the effect of intra-accumbens administration of GABABreceptor agonist and antagonist on the expression and acquisition of morphine-induced conditioned place preference (CPP) in morphine-sensitized rats was investigated.Methods: In a pilot study, different doses of morphine (0.5, 1, 2.5, 5 and 7.5 mg/kg) were administered to the morphine-naive animals in order to identify ineffective doses of the drug. Sensitization was induced by subcutaneous (s.c.) injection of morphine (5 mg/kg; once daily for 3 days) followed by five days resting. After the period of sensitization, on the day 9, place conditioning was induced using ineffective dose of morphine (1 mg/kg, s.c.). GABAB receptor agonist, baclofen (1.5, 6 or 12 mg/rat)or GABAB receptor antagonist, CGP35348 (1.5, 6 or 12 mg/rat)were injected into the shell part of nucleus accumbens acutely 5 min before the test of CPP (expression of CPP) or 10 min before each injection of morphine (acquisition of CPP).Results: The results indicated that injections of baclofen (1.5 and 12 mg/rat) educed the expression of morphine CPP in morphine-sensitized rats. Baclofen (1.5 and 12 mg/rat) also reduced the acquisition of morphine CPP in morphine-sensitized rats. Injections of CGP35348 (6 and 12 mg/rat) reduced the expression of morphine CPP in morphine-sensitized rats. CGP35348 (6 mg/rat) administration also reduced the acquisition of morphine CPP in morphine-sensitized rats.Conclusion: In conclusion, these results confirm the modulator role for GABAB receptors within the shell part of nucleus accumbens in the acquisition and expression of morphine-induced place conditioning in morphine-sensitized rats.

Introduction: Embryonic stem cells (ESCs) isolated from mouse blastocyst are genetically normal pluripotent cells and are able to differentiate to all types of cells. Study of mechanism of differentiation of these cells to neural cells could help us to know the mechanism of central nervous system development and finding better strategies for stem cell based therapies in human neurodegenerative disorders. The aim of this study was to evaluate the effect of Sonic hedgehog (Sbh), Retinoic Acid (RA), Leukemia inhibitory factor (LIF), Interleukin-6 (IL6) and nerve growth factor (NGF) on differentiation of neural progenitor cells (NPCs), produced by lineage selection method from mouse ESCs, to cholinergic neurons.Methods: Royan BI, mouse ESCs derived from C57BL/6 strain was used to produce aggregates. According to growth factor mediated lineage selection method aggregates were cultured in serum free medium to produce nestin positive or NPCs, then cell expansion was achieved by treatment with EGF and FGF2. Following withdrawal of EGF and FGF2, the cells were further cultured in presence or absence of differentiation factors: LIF, Sbh, RA, NGF and IL6 in serum containing medium. Relative number of neurons and cholinergic neurons were assessed by immunocytochemical procedure using antibodies against MAP2, b-tubulin 3, and ChAT.Results: Data obtained show that around 70% of the cells were b-tubulin 3 positive. We found different percentage of cholinergic neurons from 10-20% in cultured cells in different groups. RT-PCR analysis showed that cholinergic specific genes were also expressed in cultured cells.Conclusion: This study shows that some of the neurons produced by lineage selection method are cholinergic neurons and the percentage of cholinergic neurons increases after treatment by Sbh, LIF and RA.

Introduction: Few studies have investigated the effect of exercise on homocysteine and 15-F21-isoprostanein animal models. The present study was designed to examine the effect of long-term exercise and/ or high cholesterol diet on MDA, 15-F21-isoprostane and total homocysteine in the aorta and plasma of rabbits.Methods: 56 male rabbits were divided into four groups: normal diet (control), normal diet with exercise, high-cholesterol diet without exercise and high cholesterol diet with exercise. Animals of exercise groups ran on a treadmill at 0.88 km/h for 7.5 -90 minlday (5 days/week) for 12 weeks. At the end of exercise protocol, blood samples were collected and tHcy, 15-F21-isoprostane were measured using enzyme immunoassay (EIA) kits. MDA levels were determined by the thiobarbituric acid assay. Thoracic aorta was isolated to evaluate atherosclerosis as well as tHcy, 15-F21-isoprostaneand MDA levels.Results: Exercise reduced atherogenic diet-induced atherosclerotic lesions in aorta along with positive changes in plasma cholesterol profile. Atherogenic diet significantly increased plasma and aorta concentrations of MDA and tHcy. Exercise significantly reduced diet-increased plasma and aorta concentrations of 15-F21-isoprostaneand tHcy in normal animals. MDA levels did not show significant change due to exercise and!or high cholesterol diet feeding. There was a positive correlation among plasma cholesterol, homocysteine and 15-F21-isoprostane in exercised groups compared with control.Conclusion: Our results suggest that elevated homocysteine level can be considered as one of the multiple risk factors in the development of atherosclerosis. In addition, exercise may effectively reduce plasma and aorta homocysteine and 15-F21-isoprostane and may be effective in prevention and attenuation of atherosclerosis.

Introduction: Prolonged and intermittent oxygen pre-exposure is associated with protection against ischemic reperfusion (IR) injury. In the current study, attempts were made to investigate the relationship between exposure to prolonged and intermittent normobaric hyperoxia (NBHO) and expression of excitatory amino acids transporters (EAATs) and TNF-a level.Method: Rats were divided into four main experimental groups, each of 21 animals. The first two were exposed to 95% inspired NBHO 4 h/day for 6 consecutive days (intermittent NBHO) or for 24 continuoushours (prolonged NBHO).The second two groups considered as controls and were exposed to 21% oxygen in the same chamber (normobaric normoxia, NBNO). Each main group was subdivided to MCAO (middle cerebral artery occlusion), sham-operated (without MCAO) and intact (without any surgery) subgroups. After 24h, MCAO subgroups were subjected to 60 min of right MCAO. After 24 h reperfusion, neurologic deficit scores (NDS) were assessed in MCAO-operated subgroups. Immediately and 48 h after pretreatment, blood sampling were done for assessing level of serum TNF-a. The effect of intermittent and prolonged NBHO on EAATs expression level was also measured using western blotting.Result: Preconditioning with prolonged and intermittent NBHO decreased NDS and up-regulated EAATl, EAAT2, and EAAT3, significantly. Also, oxygenexposure of prolonged and intermittent NBHO increased the level of senun TNF-a.Conclusion: Although further studies are needed to clarify the protective mechanisms OF hyperoxia, the intermittent and prolonged NBHO seems to partly exert their effects via increasing the serum level of TNF-a and up regulation of glutamate transporters. However, the intermittent NBHO seems to have appropriate effects with low toxicity.

Introduction: Mechanoreceptors of foot sole likely contribute in the reflex regulations. Stimulation of these receptors in the lateral aspect of the foot is corresponded to the lateral plantar division of the tibial nerve. Therefore, it was hypothesized that repetitive low threshold afferents stimulation would have an inhibitory effect on the soleus H-reflexes.Methods: Sixteen normal subjects voluntarily participated in this study and were randomly allocated. Subjects were remained in prone position. The cutaneous mechanical pressure (CMP) equal to 50% of leg and foot weight was applied to the ipsilateral lateral plantar surface using a special instrument through a square plate (30x30 mm). H reflexes as indicator for excitability of motoneurones was bilaterally elicited before and after the application of the CMP and the Hreflex parameters were measured.Results: The amplitude of H reflex and HIM ratio showed significant differences before and after the ipsilateral CMP stimulation of the lateral side of the foot (p<0.05; p<0.05, respectively decreased). Furthennore, the latencies of H reflexes were also increased (p<0.05).Conclusion: Our results highlight the modulatory effects of natural stimulation of cutaneous afferents on excitability of ipsilateral and contralateral motoneurones. This in respect may have practical application in the management of muscle tone disorders following brain and spinal cord injuries.

Introduction: Neuropathic pain may be due to a primary insult to the peripheral or central nervous system. It seems that immune cells play an important role in the development and maintenance of chronic pain. Nimesulide, a highly selective CoxII inhibitor, effectively reduces hyperalgesia due to peripherally administration of inflammatory agents like formalin. In this study we have investigated the effect of nimesulide on pain behavior and CoxII expression in macrophage and tnicroglial cells in neuropathic pain condition.Methods: Male Wistar rats (150-200 g) were divided into 5 different groups: 1) CCI + saline 2) Sham + saline (control), 3) CCI + Nimesulide (1.25, 2.5 or 5 mg/kg). Neuropathic pain was induced using Bennet and Xie model. Warm water (42°C) for thermal hyperalgesia and Von Frey filaments for mechanical allodynia were respectively used as pain behavioral tests. Experiments were performed on day before and days 1, 3, 5, 7, 10 and 14 days post injury. At day 14 rats which received nimesulide 5 mg/kg were killed and CoxII was assessed in macrophages and tnicroglial cells. Results: Nimesulide 2.5 and 5mg/kg reduced hyperalgesia and allodynia. Nimesulide 5 mg/kg also reduced Coxn expression in macrophages and tnicroglial cells compared to CCI + saline group.Conclusion: Nimesulide reduced hyperalgesia due to nerve inflammation. CoxII -induced PGs activates a wide range of immune cells like macrophages and tnicroglia. It seems that nimesulide a highly selective CoxII inhibitor can reduce effectively neuropathic pain.

Introduction: In the current study, protective effect of natural honey applied during ischemia/reperfusion (I/R) was studied on infarct size in ischemic heart.Methods: Ischemic heart hearts (n=8 per group) were mounted on a Langendorff apparatus at constant pressure then subjected to 30 min regional ischemia followed by 120 min reperfusion. In control group, the hearts were perfused by a modified Krebs-Henseleit solution throughout the experiment, however, in the test groups they were perfused by Krebs solution enriched by natural honey (0.125, 0.25, 0.5 and 1%). At the end of reperfusion, the infarct size was determined by triphenyltetrazolium chloride and computerized planimetry methods.Results: The results showed that perfusion of ischemic heart hearts with natural honey produces significant reduction in infarct size and volume of infracted tissue. In the control group, infarct size was 45.6±3.4%, while honey (0.125, 0.25, 0.5 and 1%) reduced it to 14.8±5.1 (p<0.001), 24.6±7.3 (p<0.01), 31.4±7.3 (p<0.05) and 42.6±6.1% (p>0.05), respectively. In addition, infracted volume was lowered from 229±22mm3 (control) to 78±26 (p<0.001), 120±30 (p<0.01), 160±31 (p<0.05) and 201±45 mm3 (p>0.05), respectively.Conclusion: The results of this study showed protective effects of natural honey against I/R injuries as education of infarct size. Probably, antioxidant activity of honey, scavenging of free radicals and presence of energy sources such as glucose are involved in its cardio protective effect. Lower honey concentration seems to be more effective.