Physiology and Pharmacology
Year:2007 | Volume:11 | Issue:1|Papers Count:16

Introduction: Dark neurons which their morphological characteristics are consistent with those of cells undergoing apoptosis, are generated as an acute or delayed consequence of several pathological situations. The present study was designed to evaluate whether inflammatory pain regarding the role of NO and JNK lead to the formation of dark neurons in the dorsal horn of the lumbar spinal cord in rats.Methods: Acute or chronic inflammatory pain was induced by intraplantar injection of 1%, 2.5% or 5% formalin in male Wistar rats weighing 250-300 g (n=7). Spectrophotometrical analysis of the serum nitrite (metabolite of NO) and histological procedures for detection of dark neurons were performed at definite time intervals. Pretreatment with celecoxib 10, 20 or 40 mg/kg/i.p.; quercetin 40 or 100 mg/rat/i.t. as an inhibitor of JNK pathway, and PTIO 20 or 30 mg/rat/i.t, as NO scavenger, were performed to investigate the role of NO and JNK. Results: Injection of formalin led to the increase of the serum nitrite in the concentration and time-dependent manners. The effect of 5% formalin was significantly eminent which was blocked by celecoxib 40 mg/kg. Visual inspections of the spinal cord sections showed that on day 5, following chronic injections of 5% formalin, numbers of dark neurons were significantly increased in the lumbar dorsal horn. Acute and chronic administration of other concentrations of formalin did not induce any remarkable dark phenotype. Injections of celecoxib 40 mg/kg, quercetin 100 mg/rat/i.t. or PTIO 30 mg/rat/i.t. before each injection of 5% formalin, led to a reliable reduction of dark neurons. Conclusion: The results showed that the intensity and duration of the inflammatory pain play a major role in its peripheral and central developed disorders. According to the role of NO and JNK; it seems that administration of their inhibitors, or an appropriate dose of celecoxib may exert a protective effect against the aforementioned consequences.

Introduction: Low-frequency stimulation (LFS) has a delaying effect on kindled seizures acquisition. In the present study we examined the role of galanin receptors in the inhibitory effects of LFS on kindled seizures induced by electrical stimulation of perforant path.Methods: Animals were stimulated daily at the AD threshold intensity with a rapid kindling procedure. LFS was applied immediately after cessation of each kindling stimulation. M35 (0.5 and 1.0 nM per site), a nonselective galanin receptor antagonist, was microinjected daily into the dentate gyrus before the beginning of stimulation protocol and behavioral seizure stages and after discharge durations were recorded. Results: LFS application had a suppressive effect on the kindling rate. It significantly increased the number of stimulations needed to reach seizure stages 3, 4 and 5. LFS also decreased the cumulative after discharge duration during the days of stimulation. Intra-dentate gyrus microinjection of M35 reduced the inhibitory effect of LFS on kindling rate, significantly.Conclusion: These data indicate that galanin receptors may have a role in mediating part of the inhibitory effects of LFS on perforant path kindled seizures.

Introduction: Topiramate is a newly anti-convulsant drug, which acts as NMDA glutamate receptor antagonist as well as the GABAB receptor agonist. It is used for physical dependence to opioids as well as cocaine, nicotine, alcohol and ecstasy dependence. In the present study attempts were made to further identification of the effects of topiramate on the acquisition and expression of morphine-induced conditioned place preference and behavioural sensitisation in mice.Methods: Male Swiss-Webster mice were used. Conditioned place preference and locomotion were assessed by an un-biased place conditioning paradigm and open filed methods. In a pilot study, the effects of morphine and topiramate on place conditioning paradigm as well as locomotion were assessed in morphine-nave animals for evaluation of effective and ineffective doses of the drugs. Different doses of topiramate were injected to the animals 30 min before each morphine injections (acquisition) or 30 min before the experiments were beginning on the test day.Results: Administration of different doses of morphine (0.5, 5 and 50 mg/kg) induced locomotor activity in the animals. In addition, morphine (1, 10 and 20 mg/kg) administration also induced place preference. On the other hand, administration of different doses of topiramate (20, 80 and 120 mg/kg) neither induced place preference nor altered animals’ activity. Topiramate administration (20 and 80 mg/kg) and (80 and 120 mg/kg) reduced the acquisition and expression of morphine-induced place preference, respectively. In addition, topiramate (20, 80 and 120 mg/kg) reduced the acquisition of morphine-induced behavioral sensitization where as the drug in dose 80 mg/kg enhanced the expression of morphine-induced behavioral sensitization.Conclusion: It can be concluded that topirmate administration interacts with the euphoric and locomotor properties of morphine and this can be considered in therapeutic usage of the drug.

Introduction: There are several evidences that show various environmental stresses during pregnancy, affect physiological behavior of the offspring. In this study the effects of REM (Rapid Eye Movement) sleep deprivation of pregnant rats on spatial learning of adult male offspring by Morris water maze were investigated. Methods: Water tank technique was used for inducing REM sleep deprivation. Pregnant rats were deprived for 3 days (E14, E15 and E16; or E17, E18 and E19) on a small platform (diameter: 5.5 cm) or a large platform (diameter: 19 cm) (sham). Undeprived (control) pregnant rats offspring were also used. Learning indices of the male offspring was evaluated using MWM.Results: Our results showed that the traveled distance to locate on hidden platform in target quadrant and latency to find the hidden platform were decreased significantly in offspring of REM sleep deprived and sham animals (P<0.05). Conclusion: Based on our results, it seems that, applied range of stress which is executed through the sleep deprivation could cause increase in spatial learning of adult male offspring rats.

Introduction: Several studies have indicated that late treatment of aminoguanidine (AG) reduces cerebral ischemic injuries in animal models. However, the effects of early treatment of AG on cerebral ischemic damage are not well understood. This study was designed to evaluate effect of early treatment of AG on cortex and striatum injuries as well as neurological dysfunctions in transient model of focal cerebral ischemia. Methods: Rats (n=30) were assigned to control or AG treated groups (75 or 150 mg/kg, i.p.,). Ischemia was induced by 60 min middle cerebral artery occlusion, followed by 24h reperfusion. Saline (control) or AG were administered at the onset of the ischemia. Twenty-four hours after the end of ischemia, neurological dysfunction scores were determined and then the infarct volumes of cortex and striatum were measured. Results: Administration of AG (75 and 150 mg/kg) at the beginning of ischemia, significantly reduced cortical and striatal infarct volumes by 47%, 69% and 42%, 36%, respectively (p<0.001). Moreover, AG only at dose 150 mg/kg significantly improves neurological dysfunction (p<0.01). Conclusion: Results of this study indicated that administration of AG in early phase of focal cerebral ischemia reduced cortical and striatal infarct volumes and improve neurological deficits in rat model of transient focal cerebral ischemia.

Introduction: Mental stress is one of the most important causes of the gastric ulcer. On the other hand, flavonoids such as quercetin show protective effects. The aim of this study was to investigate possible protective effect of quercetin on water restraint stress-induced ulcer in rats.Methods: Adult male Wistar rats were divided into seven groups each containing eight animals. The first group (S) received normal saline (5 ml/kg, p.o.) and groups 2-7 received normal saline, quercetin 25, 50, 100, 200 (mg/kg, p.o.) or omeprazole (20 mg/kg, s.c.) respectively. After I hour, all animals except the first group (S) were placed into the plexiglass restrainers and kept in water (23°C) for 3.5 hours. After another 3.5 hours interval, rats were scarified and volume of gastric output, pH, acid content and ulcer index (VI) were measured.Results: pH of gastric content in QS50-QS200 groups was lower than the saline/stress (SS) treated group (P<0.05).The gastric acid content in the saline treated group was higher than SS, quercetin/stress (QS) 50 and QS 200 groups (P<0.05) and higher than omeprazole/saline (OS) group. Omeprazole inhibited the gastric acid secretion. The VI in the QS25 and QS50 groups were lower than of SS group (P<0.05 and P<0.001 respectively) The VI in the QS100 and QS200 groups were identical to SS group. The VI in S and OS groups was approximately zero.Conclusion: The results of this study suggest the protective effect of quercetin in stress-induced gastric ulcer test. However this protective effect is not precisely dose independent.

Introduction: Traditional Iranian medicine (TIM) is accompanied by little side effects in experience. The mechanisms involved in TIM are not much clear. The purpose of this study is assessment of differences of warm and cold nature persons in neuroendocrine system and cytokine pattern (Th1/Th2) of immune responses.Methods: Thirty seven 20 to 40 years old male volunteers were divided into 2 groups of warm and cold nature using a standard questioner. Warmth/coldness ratio of all volunteers was assessed according the results of the questioner. Plasma concentrations of epinephrine, norepinephrine, cortisol and the concentration of IFN-g and IL-4 produced by peripheral blood mononuclear cells were measured. Results: The results showed that norepinephrine/epinephrine and norepinephrine/cortisol ratios in the hot nature volunteers were significantly more than cold nature volunteers. The IL-4/IFN-g ratio in the hot nature group was more than in the cold nature group and this difference was approximately significant (P = 0.08). Also there was a significant positive linear correlation between the norepinephrine/epinephrine and warmth/coldness ratio (P = 0.008) and a nonlinear significant association between IL-4/IFN-g and warmth/coldness ratio (P = 0.022). Conclusion: Therefore, it can be deduced that the hot nature persons had a more peripheral sympathetic nervous system activity, less adrenal sympathetic, adrenal corticosteroid and parasympathetic nervous system activities and more deviation of immune system toward Th2 responses. Also the activity of sympathetic nervous system was increased and adrenal sympathetic was decreased with growing of warmth/coldness ratio. When the nature went toward severe warmth or severe coldness, the deviation of immune system toward Th2 like responses would increase, but this increasing was very more severe with going toward severe warmth than that of going toward severe coldness.

Introduction: The effect of esophageal distension (ED) on gastric motility has been well documented, but a few investigations have been carried out on the effect of ED on gastric secretion. The aim of this study was to investigate the effect of ED on gastric acid and pepsin secretion and the mechanism(s) involved. Methods: Male adult Wistar rats (200-240 g) were anesthetized with urethane (1.2 g/kg, i.p.) and underwent tracheostomy and laparotomy. A catheter was inserted in the stomach through duodenum for gastric distension and gastric washout. Esophagus was distended by a balloon (0.3 ml, 10 min). Gastric acid secretion was stimulated by gastric distension (by saline 1.5 ml/100 g of B.W.), pentagastrin (20 μg/kg, i.p.) or insulin (0.6 IU/kg, i.p.). Pepsin secretion was stimulated by carbachol (20 μg/kg, i.p.). Effects of cervical vagotomy and reserpine (1 mg/kg, i.p.) were also investigated. Results: Gastric distension-, pentagastrin- and insulin-stimulated gastric acid secretion were decreased by esophageal distension (P<0.001, P<0.05 and P<0.05, respectively). Carbachol-induced pepsin secretion was also attenuated by esophageal distension (P<0.05). Cervical vagotomy abolished the inhibitory effect of ED on gastric distension-induced acid secretion. In reserpinized rats, ED reduced the basal gastric acid secretion (P<0.05). Conclusion: Results indicated that the ED decreased gastric acid output. The vagus nerve was involved in the inhibitory effect of the ED on gastric acid secretion but the adrenergic system did not play role.

Introduction: Urine morphine test, in several countries is the most primarily available qualitative test for detecting opioid abusers. Since the users of illicit drugs attempt to defeat urine tests and there are also plenty of claims that usage of HD (high dose) contraceptive pills can result in false-negative results, we decided to design the present study to investigate the probable in vitro and in vivo interaction of HD contraceptives and urine morphine diagnostic test. Methods: Several high and low concentrations of ethinylestradiol (EE), levonorgestrel (LN), and both of them were made in the blank urine and urine samples obtained from morphine abusers and then were detected by Acon® urine test strips. Also, high and low doses of EE, LN, and both of them were administered orally to separate groups of control, morphine dependent, and morphine treated (20 mg/kg in single dose, s.c.) male Wistar rats (225 ± 25 g). The urine samples were collected during 3-6, 12-15, 21-24 h time intervals in metabolic cages and were examined by Acon® urine tests.Results: Neither contraceptive constituents nor their urine metabolites at different levels were able to negate the results of urine kits.Conclusion: We conclude that there is no interaction between HD contraceptives and urine morphine diagnostic tests both in vitro and in vivo. It is recommended to inform the results of this study to withhold further misusage of contraceptives and their possible adverse effects.

Introduction: Some studies indicate changes in the level of thyroid hormones in addicted people. Also, there are some reports concerning the modulation of hypothalamus-hypophysis-thyroidaxis in the context of morphine addiction. In the present study, the effects of thyroid gland activation via the acute and chronic administration of levothyroxine on morphine withdrawal syndrome were investigated.Methods: Frothy two adult male mice were divided into 6 groups. Animals received three daily injections of morphine (20, 40, 80 mg/kg) alone or in combination with I-thyroxin (0.5 mg/kg, i.p: single dose, chronic for 4 days and chronic for 16 days). Morphine withdrawal syndrome was induced using naloxone. Withdrawal signs such as jumping, rearing, climbing and weight loss were recorded for 30 minutes.Results: The results showed that acute levothyroxine administration increased the morphine withdrawal signs. Four days administration of levothyroxine reduced the number of jumping and climbing and inhibited weight loss.Administration of levothyroxine for 16 days reduced only the number of rearing.Conclusions: It seems that levothyroxine via alteration of thyroid hormones level can affect morphine withdrawal signs and this effect of levothyroxine can be attenuated with its repetitive administration.