Physiology and Pharmacology
Year:2009 | Volume:13 | Issue:2|Papers Count:18

Introduction: Chronic morphine exposure can cause addiction and affect synaptic plasticity, but the underlying neural mechanisms of this phenomenon remain unknown. Herein we used electrophysiologic approaches in hippocampal CA1 area to examine the effect of chronic morphine administration on short-term plasticity. Methods: Experiments were carried out on hippocampal slices taken from either control animals or animals made dependent via oral chronic morphine administration. Population spikes (PSs) were recorded from stratum pyramidale of CA1 following stimulation the Schaffer collateral afferents. For examining the short-term synaptic plasticity, paired pulse stimulations with inter pulse interval (IPI) of 10, 20, 80, and 200 ms were applied and paired pulse index (PPI) was calculated.Results: Chronic morphine exposure had no effect on the baseline response. A significant increase in PPI was observed in dependent slices at 80 ms IPI as compared to the control ones. There was no significant difference in baseline response between control and dependent slices when we used long term morphine, naloxone, and both. However, long term morphine administration caused significant difference in PPI at IPI of 20 ms. This effect was eliminated in the presence of naloxone.Conclusion: These findings suggest that morphine dependence could affect short-term plasticity in hippocampal CA1 area and increase the hippocampus network excitability.

Introduction: Cannabis consumption during pregnancy may affect fetal growth, motor performance, memory and cognitive functions.Methods: Primiparous pregnant Wistar rats were randomly assigned to 4 treatment groups (6 rats per group) consisting of control and sham groups as well as 2 groups treated with Win. Win treated groups received daily s.c. injections of 0.5 or 1 mg/kg WIN suspended in 1% Tween 80 saline in a volume of 1 ml/kg from days 5 to 20 of pregnancy. Sham treated rats were given daily injections of 1% Tween 80 saline on the same days of pregnancy. Body weight, mortality, memory function and motor performance were assessed in the infants on the third, fifth and seventh weeks after birth. Righting responses in rat pups were also compared on the second day after birth. Results: Offsprings from Win (1mg/kg) treated rats exhibited a significant loss in the righting reflex on the 2nd day after birth, when compared to other groups. However, there was no statistically significant difference between groups regarding motor coordination assessed by rotarod test on the 3rd and 5th weeks after birth. Passive avoidance learning (PAL) test on 50-day-old rats showed that during the acquisition trials, approach latencies were not significantly different among all groups. However, in retention trials, which were performed 24 h and 7 days later, the avoidance latencies of rats exposed to 0.5 mg/Kg Win were significantly shorter than those of the control and sham animals. Win consumption during pregnancy did not induce significant changes in the body weight of pregnant rats on the first day and three weeks after pregnancy. Litter size (number of pups per delivery) was significantly reduced in 1 mg/kg Wintreated compared to 0.5 mg/kg Win-treated, sham treated and control groups (p<0. 001). The length of pregnancy in 1 mg/kg Win-exposed rats was also significantly shorter compared to control (p<0.001), 0.5 mg/kg win-treated (p<0.01), and sham (p<0.0001) rats. Conclusion: These findings suggest that prenatal exposure to Win, a cannabinoid agonist, probably induces a longterm alteration of the endocannabinoid system, which in turn affects learning and motor coordination ability.

Introduction: Paraoxon is the neurotoxic metabolite of organophosphorus (OP) insecticide parathion and causes acute toxicity by inhibition of acetylcholinesterase (AChE). AChE inhibition leads to the accumulation of acetylcholine in cholinergic synapses and hence results in an overstimulation of the cholinergic system. Reports on changes in the level of g- amino butyric acid (GABA) during OP-induced convulsion have been controversial. In the present study we used cortical and hippocampal synaptosomes from rats after paraoxon poisoning to study the alterations of GABA uptake.Methods: Male Wistar rats (200-270 g) were used in this study. Animals were given a single intraperitoneal injection of corn oil (control group) or paraoxon (0.1, 0.3, or 0.7 mg/kg). [3H] GABA uptake by cortical and hippocampal synaptosomes was measured 30 min, 4 h, and 18 h after exposure (n = 7 rats/group). Type of transporter involved in the uptake was also determined by using b-alnine and L-diaminobutyric acid (L-DABA), which are glial and neuronal GABA uptake inhibitors, respectively.Results: GABA uptake was significantly (p<0.001) reduced by both cortical (18-32%) and hippocampal (16-21%) synaptosomes compared with their respective control groups at all 3 time points after administration of the convulsive dose (0.7 mg/kg) of paraoxon. b-alnine had no inhibitory effect on the uptake, whereas L-DABA abolished most of the transporter mediated GABA uptake.Conclusion: Our results showed that GABA uptake did not change in groups treated with 2 lower doses of paraoxon, which may indicate that the decrease of GABA uptake is convulsion-related. The decrease in GABA uptake, which is probably due to a change in the function of GABA transporters, may represent a compensatory response modulating neuronal overexcitation. Most of synaptosomal GABA uptake was blocked by L-DABA, indicating that the uptake was primarily carried out by a neuronal GABA transporter (GAT), GAT-1.

Introduction: Sex differences have been repeatedly observed in chronic pain; therefore it is likely that the gonadal hormones are involved in nociception. On the other hand, different experimental models have been created to investigate the responsible mechanisms of chronic pain. This study examines the effects of gonadal hormones on nociceptive responses of rats in the CCI (chronic constriction injury) and SNI (spread nerve injury) models. Methods: Male rats underwent gonadectomy or sham surgery 2 weeks before nerve injury. A plantar analgesic meter was used to measure gonadectomy-induced changes in paw withdrawal latency (PWL) values, and von Frey monofilaments and Randal selitto test were used to assess changes in the paw withdrawal threshold (PWT) in response to mechanical stimuli. Animals were subjected to the behavioral tests before induction of nerve injury. Behavioral tests were also performed 1 week after nerve injury and were then repeated once a week for 3 weeks. t-Test and Mann- Whitney were used for statistical analysis.Results: The data revealed that PWL and PWT values were the same in these two nerve injury models and PWL was significantly lower in gonadectomized rats compared to sham group. There were no gonadectomy-related differences in the development of mechanical allodynia. Also it seems that mechanical hyperalgesia is more affected by sexual hormones in SNI model during the first week after nerve injury. Conclusion: These findings demonstrate that CCI and SNI models induce similar nociceptive behaviors in rats and mechanical and thermal nociceptive responses are differentially affected by gonadal hormones in male rats.

Introduction: In recent studies, both endothelium-dependent and endothelium-independent mechanisms have been reported for the action of b-adrenoceptors. The aim of this study was to investigate the role of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) in β2-adrenoceptors (b2-AR) mediated vasodilation in rat skin vessels. Methods: All drugs were injected subcutaneously into the plantar skin of the hind paw. Injection volume was 10 ml (5ml/min). Induction of anesthesia was performed with urethane 1.5 g/kg. Laser Doppler Flowmetery (LDF) technique was used to monitor the skin blood flow (SBF).Results: The results obtained in this study showed that different doses of salbutamol, a selective b2-AR agonist (1mM), caused a significant increase of SBF, but effects induced by different doses of salbutamol were not significantly different. Atenolol, a selective b1-adrenoceptor antagonist (10 mM), alone and with salbutamol had no significant effect on SBF. Propranolol, a non selective b-adrenoceptor antagonist (1 mM), did not changed SBF by itself, but significantly reduced the vasodilatory effect of salbutamol. LNNA, a NO inhibitor (10mM) and methylen blue, a cGMP inhibitor (3mM), caused significant decreases in SBF equal to 6.95% and 7.91%, respectively. Salbutamol injection after LNNA and NO raised the SBF to 24.7% and 22.5%, respectively. These values were significantly lower than the value observed for salbutamol (42.73%).Conclusion: The results indicated that, salbutamol dilates rat skin vessels via b2- ARs. NO and cGMP are involved in b2-ARs mediated vasodilation and contributed to the regulation of skin vascular tone. More studies are required to elucidate the exact mechanism of function of b2-adrenoceptors.

Introduction: Dual pathways have a crucial role in causing atrio nodal tachyarrhythmias (AVNRT). The aim of the present study was to determine the role of slow pathway (SP) in the concealment zone and also the protective role of AV node during atrial fibrillation (AF).Methods: In 7 isolated nodal rabbit preparations, zones of concealment and concealed conduction were determined by specific pacing protocols. The differences between effective refractory period of atrial and AV node in the basic cycle length and after introducing concealed beat was considered as the zone of concealment. AF was simulated by high-rate atrial pacing with random coupling intervals. Small miniature lesions were made in superior compact node by delivering constant voltage100-110 v.Results: Fast pathway (FP) ablation resulted in longer minimum nodal conduction time, but did not induce any change in nodal effective and functional refractory period. Zone of concealment was determined as 10 ± 4.8 ms. After fast pathway modification, nodal characteristics during AF, including average H–H intervals, number of concealed beats and zone of concealment did not change significantly.Conclusion: Fast pathway has not a determinant role in the mechanism of concealed conduction and zone of concealment. Our findings indicate that during AF, the wave fronts did not use fast pathway to conduct to ventricles.

Introduction: Previous studies in male and female mice have shown that administration of saffron extract could induce reward and reduce morphine reward as investigated by place preference and behavioral sensitization. In the present study, the effects of water extract of Crocus sativus on the acquisition and expression of tolerance to morphineinduced hyperalgesia in female N-MRI mice (20-25 g) were investigated.Methods: Tail Flick technique was used in the present study. Morphine tolerance was achieved by morphine injections 50 mg/kg, twice daily for 3 consecutive days. On the 4th day of the experiments, morphine tolerance was assessed in animals by injection of effective dose of morphine (10 mg/kg). The extract of the C. sativus was administered during or after the induction of morphine tolerance, to assess its effect on the development and expression of tolerance, respectively. Results: Results showed that administration of morphine (1, 5, 10 and 20 mg/kg), induced significant analgesia in mice. Administration of the plant extract (1, 2.5, 5, 10, 50 and 100 mg/kg) also produced analgesia, which was statistically significant with the 10 mg/kg dose. Injection of saffron extracts (1, 2.5 and 5 mg/kg) on the test day, 30 min before morphine administration (10 mg/kg) reduced the expression of morphine tolerance. However, administration of the extract (1, 2.5 and 5 mg/kg) during the induction of morphine tolerance, did not have any effect on the development of morphine tolerance.Conclusion: It could be concluded that injection of the extract of C. sativus can inhibit the expression but cannot alter the acquisition of morphine tolerance. In addition, administration of the extract alone could also induce analgesia.

Introduction: The antidiabetic effects of garlic juice on blood glucose levels and pancreas tissue was evaluated in STZ-induced diabetes in rats.Methods: 40 male rats were divided into 5 groups of 8 as follows; 1) Normal group (N); 2) Normal + Garlic group (N+G): received 1 ml garlic juice/100g BW/day for 6 weeks; 3) Diabetic group (D): were injected with streptozotocin (60 mg/kg BW, i.p.); 4) Diabetic + Garlic-before group (D+Gb): received garlic juice for 6 weeks and were injected with STZ at the end of the third week; 5) Diabetic + Garlic-after group (D+Ga): received garlic juice for 3 weeks, after being injected with STZ. At the end of the experiment, serial sections of pancreas were prepared and stained with H&E for light microscopic investigations. Results: Serum glucose levels were significantly increased (p<0.0001) in D group in comparison with other groups. There was no significant difference between D+Gb group and N and N+G groups. Body, pancreas, and relative weights were significantly decreased (p<0.05) in D group in comparison with other groups. In D+Gb and D+Ga groups pancreas weight showed no significant difference with the normal group. In D group a decrease of pancreatic islet numbers and their mean diameter, as well as atrophy and vacuolation of pancreatic islets parenchyma were detected. These abnormal histological signs were dramatically decreased in D+Gb group compared to D group. Also in D+Ga group, considerable effects of garlic juice on the histopathological changes of the pancreas were noted, but these effects were not as dramatic as in the D+Gb group.Conclusion: Based on these results, it is suggested that garlic juice has favorable effects in preventing changes in blood glucose levels, body and pancreas weights, and the histopathological changes of pancreas in STZ-induced diabetes.

Introduction: The existence of a close relationship between energy status and reproductive function is well documented, but its underlying mechanisms remain to be fully unfolded. Galanin is an orexigenic agent and has been demonstrated as putative regulator of gonadotropin secretion in rats. There is no study to show the interaction of different levels of energy intake and galanin on gonadotropins secretion in ruminants, therefore the goal of this study was to determine whether galanin affects the mean plasma concentrations of LH and FSH in the female Saanen goats fed diets with different energy contents. Methods: Nine female Saanen goats were randomly divided into 3 groups. Animals were fed a diet containing 50%, 100% or 150% of their energy requirement for one month. After one month, goats received 1 mg galanin /kg body weight into their jugular vein. Blood samples were collected every 30 minutes from jugular vein of all goats 3.5h before and 3.5h after the injection of galanin. Blood plasma was assayed for plasma LH and FSH concentrations by RIA. Results: Injection of galanin significantly decreased the mean plasma concentrations of LH and FSH only in the 150% dietary energy intake group, whereas in 50% and 100% dietary energy intake groups injection of galanin had no effect on plasma gonadotropin levesl. Conclusion: These results indicate that galanin may negatively affect mean plasma concentrations of LH and FSH only in female Saanen goats with positive energy balance.

Introduction: Acute respiratory disorders such as obstructive pulmonary diseases and hypoventilation may lead to alveolar hypoxia and hypercapnia. The effect of these events on the pulmonary vascular beds remains controversial. The aim of this study was to establish an isolated perfused lung setup and investigate the effects of alveolar hypoxia and hypercapnia on pulmonary vascular resistance.Methods: White New Zealand rabbits were anaesthetized, heparin was administered as anticoagulant and trachea was cannulated. Then the lung was exposed and perfused with Krebs solution through a pulmonary artery cannula. The ventilated-perfused lung was carefully excised from the chest and the healthy lungs were randomly divided into three groups (n = 7 each group). Ventilation was performed for 30 min with normoxic-normocapnic, hypoxic-normocapnic, or hypoxic-hypercapnic gas mixtures. The percent changes of pulmonary vascular resistance per min (%PVR) and their maximum values were evaluated.Results: Hypoxic-normocapnic ventilation resulted in an initial sharp rise in PVR that reversed to a slow decline after 8 min of exposure. After 12 min of exposure, a second steady rise in PVR occurred and continued until the end of the experiment. The rate of rise of PVR during hypoxic-hypercapnia was steeper (17.3 ± 2.4% /min) compared to hypoxic-normocapnia (8.86 ± 1.6% /min), but the maximum increases observed in PVR were similar in both conditions.Conclusion: In the isolated ventilated perfused lung, acute alveolar hypoxia had a complex influence on PVR and the combination of hypoxia with hypercapnia transiently strengthened PVR without affecting its maximum level.

Introduction: Keratoconus is a relatively common disease of cornea in which structural changes within the cornea cause its thinning, change of shape and scaring in the central portion. So far, few therapeutic methods and drug treatments are available for keratoconus due to both lack of established animal models and limitation of research in humans because of ethical issues. In the present study, keratoconus was experimentally induced in mice with special focus on the role of collagen in histopathological mechanisms of the disease. Methods: Collagens (1, 3 and 6 mg/ml) was injected into the cornea of male mice. Both macroscopic and microscopic evaluations were performed in short periods of 1,3 and 5 days after injection. In macroscopic observations, eyes were graded according to the intensity of keratoconus. Microscopic observations consisted of cornea layers evaluations, presence of inflammation, changes of the cornea thickness, epithelium thickness and collagen andstroma changes.Results: Most corneal damage and assuming of a more conical shape by cornea were observed after injection of 6 mg/ml collagenase. In fact, collagenase at 3 and 6 mg/ml dose dependently caused deformity and opacity of cornea. Severe damage to collagen fibers, thinness of cornea and epithelium and in some cases corneal rupture were observed with high dose of collagenase.Conclusion: The results of the present study indicate that injection of 6 mg/ml of collagenase in the cornea of male mice induces keratoconus and this can be considered as a potential animal of the disease. Further investigations are needed to prove the validity of this animal model of keratoconus.

Introduction: Resistance exercise considerably increases the concentrations of circulating hormones such as growth hormone (GH) and testosterone. Conventional resistance exercise is performed using sequential concentric (CON) and eccentric (ECC) contractions that are performed on an external constant load. The aim of this study was to determine hormonal and metabolic responses to CON, ECC and CON-ECC muscle actions in order to develop appropriate resistance exercise protocols and equipment for both athletes and patients recovering from injury. In the present study, we have examined the endocrine system responses to six different upper and lower body exercises utilizing the CON, ECC and CON-ECC contractions.Methods: In this study, we examined acute hormonal responses of GH, total testosterone (TT), free testosterone (FT) and cortisol in 10 young men who had the experience of non-professional resistance exercise. The exercise protocol included 6 resistance exercises, Which 3 of them were upper body and the other 3 were lower body exercises. The participants performed 3 contraction actions in 3 different days with at least one week interval and at the same time of the day. The exercise protocol included 4 sets in each exercise session and 90 seconds of rest between the sets. Each set included 10 repetitions. CON and ECC actions performed at intensity of 80% CON 10-RM and 80 % (120% CON 10-RM), respectively. Considering to the counterbalanced force design and on the calculations was done, the intensity of CON-ECC action was 88% CON 10-RM. Blood samples were collected before the exercise, immediately after as well as 15 and 30 minutes after each exercise session.Results: GH was increased after CON, ECC and CON-ECC contraction exercise but this increase reached significance only after CON and CON-ECC trials. TT and FT increased significantly after all 3 types of exercise, while cortisol had a significant decrease after all types of exercise.Conclusion: Although we observed a significant increase in TT and FT and a significant decrease in cortisol levels after CON, ECC and CON-ECC contraction exercise, we did not find any significant difference among various types of exercise. This indicates that these hormonal responses after exercise is not influenced by the type of exercise. On the other hand, acute GH response after contractions depended on the type of exercise protocol, which indicates that GH response depends not only on the intensity and quantity of exercise, but also on the type of muscle contraction and degree of the motor units recruitment.

Introduction: Computer modeling of tripolar electrical stimulation has shown that this kind of electrode placement can stimulate deeper in tissues. Application of this kind of stimulation method on vertebral column in order to stimulate deep tissues in this region can be clinically beneficial.Methods: To assess the effect of penetration depth of the surface Tripolar electrical stimulation, Tripolar TENS was applied with different intensities (with 1.25 and 1.5 sensory thresholds (ST)) on the vertebral column of 20 healthy subjects. The cathode of TENS was laid on the T11 vertebra and the anodes were put 3 cm apart from the cathode longitudinally, in anode-cathode-anode arrangement. The recruitment curve of soleus and gastrocnemius H-reflex and M wave were recorded before, immediately after and 10 min after TENS. Experiments were performed in 4 separate sessions. One of the experiments was control session, during which the TENS apparatus was off during the session. In each of the test sessions, TENS was applied with one of the mentioned intensities.Results: The results showed that 1.5 ST TENS had a complex facilitatory-inhibitory effect on the recruitment curve of soleus H-reflex. With this intensity, slow motoneurons were inhibited and fast motoneurons were facilitated. Also, the positive slope of the curve was increased and the intensity needed to evoke Hmax was decreased. Furthermore, the amplitude of Hmax and the threshold of the curve were slightly decreased. Gastrocnemius was facilitated after 1.5 ST TENS and the threshold of the H-reflex curve and needed intensity to evoke Hmax were decreased, while peak to peak amplitude of Hmax was increased. After 1.25 ST TENS, soleus was facilitated and gastrocnemius had inhibitory trend. Conclusion: Tripolar TENS with 1.5 ST intensity stimulates the tissue more deeply and therefore causes different outcomes from tripolar TENS with lower STs.