Physiology and Pharmacology
Volume:13 Issue: 2, 2009

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. 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. 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. These findings suggest that morphine dependence could affect short-term plasticity in hippocampal CA1 area and increase the hippocampus network excitability.

Cannabis consumption during pregnancy may affect fetal growth, motor performance, memory and cognitive functions. 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. 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. 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.

Paraoxon (the neurotoxic metabolite of organophosphorus (OP) insecticide, parathion) exerts acute toxicity by inhibition of acetylcholinesterase (AChE), leading to the accumulation of acetylcholine in cholinergic synapses and hence overstimulation of the cholinergic system. Since, reports on changes in the level of γ- amino butyric acid (GABA) during OP-induced convulsion have been controversial, in present study we used cortical and hippocampal synaptosomes from rats after paraoxon poisoning to detect changes in GABA uptake. Male Wistar rats (200-270 g) were used in this study. Animals were given a single intraperitoneal injection of corn oil (vehicle group) or one of doses of paraoxon (0.1, 0.3, or 0.7 mg/kg) and [3H]GABA uptake by cerebral cortex and hippocampal synaptosomes was measured at 30 min, 4 h, and 18 h after the exposure (n= 7 rats/group). Type of transporter involved in the uptake was also determined using β-alnine, and L-diaminobutyric acid (L-DABA), a glial and a neuronal GABA uptake inhibitor, respectively. GABA uptake was significantly (p<0.001) reduced by both cerebral cortex (18-32%) and hippocampal (16-21%) synaptosomes compared with their respective control groups at all three time points after administering 0.7 of paraoxon (convulsive dose). β-alnine had no inhibitory effect on the uptake, whereas L-DABA abolished most of the transporter mediated GABA uptake. Since GABA uptake did not change in other two paraoxon treated groups, it may be indicating that decrement of GABA uptake is convulsion-related. The decrease in GABA uptake, presumably 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 by a neuronal GABA transporter (GAT), GAT-1.

As sex differences have been observed repeatedly in chronic pain, it is likely that the gonadal hormones are responsible for these differences. To investigate the responsible mechanism for chronic pain different models have been created. This study is examining the effects of gonadal hormones on nociceptive responses of the rats in CCI (chronic constriction injury) and SNI (spread nerve injury) model. For this reason male rats were undertaken to gonadectomy or sham surgery two 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 paw withdrawal threshold (PWT) in response to mechanical stimuli. Animals were subjected to the behavioral tests before induction of nerve injury and then once a week starting from the first week after nerve injury for three weeks. t-test and Mann-Whitney were used for statistical analysis. 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 comparing to sham group. There were no gonadetomy-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. These findings demonstrate that CCI and SNI model induces similar nociceptive behaviors in rats and mechanical and thermal nociceptive responses are differentially affected by gonadal hormones in male rats.

In recent study both endothelium-dependent and endothelium-independent mechanisms have been reported for the action of β-adrenoceptor. The aim of this study was to investigate on the role of nitric oxide (NO) and cyclic guanosin monophosphate (cGMP) in vasodilation mechanisms of β2-adrenoceptors (β2-AR) in rat skin vessels. All drugs were injected subcutaneous into planar skin of hind paw. Injection volume was 10µl (5µl/min). Induction of anesthesia was perform with urethane 1.5 g/kg. Laser Doppler Flowmetery (LDF) technique was used for skin blood flow (SBF) monitoring. The results obtained in this study showed that different doses of salbutamol, selective β2-AR agonist (1µM) caused a significant increase of SBF, but there was not any significant different in the response of different doses. Atenolol, selective β1-adrenoceptor antagonist (10µM) alone and with salbutamol had no significant effect on SBF. Propranolol, non selective β-adrenoceptor antagonist (1µM) by itself did not changed SBF, but significantly reduced the vasodilatory effect of salbutamol. LNNA, NO inhibitor (10µM) and methylen blue, cGMP inhibitor (3µM) caused a significant decrease of SBF 6/95% and 7/91% respectively. Salbutamol injection after LNNA and NO raised the SBF to 24/7% and 22.5% respectively, which shows a significant reduction in comparison to salbutamol’s effect (42.73%). The results indicated that, salbutamol dilate rat skin vessels via β2- ARs. NO and cGMP involved in β2-ARs mediated vasodilation and contribute to regulation of vascular skin tone. To elucidate the exact mechanism of this response more studies are needed.

Dual pathways have a determinant role in the occurrence of atrio nodal tachyarrhythmia (AVNRT). The aim of present study is to determine the role of slow pathway (SP) in the concealment zone and protective role of AV node during atrial fibrillation (AF). In 7 isolated nodal rabbit preparation zone of concealment and concealed conduction is quantified 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 Zone of concealment. AَF 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. FP ablation resulted in longer minimum nodal conduction time, but without change of nodal effective and functional refractory period. Zone of concealment was determined as 10±4. 8 ms. After fast pathway modification nodal characteristics during AF did not change significantly (average H–H intervals, number of concealed beats and zone of concealment). Fast pathway has not a determinant role in the mechanism of concealed conduction and zone of concealment. During AF, the wave fronts did not used fast pathway to conduct to ventricles.

Previous studies have indicated that administration of saffron extract could induced reward and reduces morphine reward as investigated by place preference and behavioral sensitization in male and female mice. In the present study, the effects of water extract of Crocus sativus on the acquisition and expression of tolerance to morphine-induced hyperalgesia in female N-MRI mice (20-25 g) were investigated. Matherila and Tail Flick technique was implicated in the present study. Morphine tolerance achived by morphine (50 mg/kg; twice daily) injections for three consecutive days. On the 4th day of the experiments, morphine tolerance was assesed in animals by injection of effective dose of morphine (10 mg/kg). The extract of the C. sativus was administered during (development of tolerance) or after induction of morphine tolerance (expression). Results showed that administration of morphine (1, 5, 10 and 20 mg/kg), induced a significant analgesia in animals. Administration of the plant extract (1, 2.5, 5, 10, 50 and 100 mg/kg) also produced analgesia which was statistically significant in dose 10 mg/kg of the extract. Injection of the plant extract (1, 2.5 and 5 mg/kg) in the test day, 30 min before morphine (10 mg/kg) reduced the expression of morphine tolerance. Administration of the extract (1, 2.5 and 5 mg/kg) during the induction of morphine tolerance, have not any effect on the development of morphine tolerance. It could be concluded that injection of the extract of C sativus can inhibit the expression but can not altered the acquisition of morphine tolerance. In addition, the extract could induced analgesia by it-self.

The preventive antidiabetic effects of garlic juice on blood glucose levels and pancreas tissue was evaluated in STZ-induced diabetic rats. 40 male rats were divided into five groups of 8 rats each. 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) injected with streptozotocin (60 mg/kg BW,i.p.), 4) Diabetic + Garlic_before group (D+Gb) received garlic juice for 6 weeks, but at the end of third week, they were injected with STZ, 5) Diabetic+Garlic_after group (D+Ga) received garlic juice for 3 weeks, after they were injected with STZ. At the end of the experiment, serial sections of pancreas were prepared and stained with H&E for light microscope investigations. Serum glucose levels were significantly increased (p<0.05) 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 was 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 decrease of pancreatic islet numbers and their mean diameter, atrophy and vacuolation in parenchyma of pancreatic islets were detected. These abnormal histological signs were dramatically decreased in D+Gb group compared to D group. In D+Ga group, dramatical but slighter effects of garlic juice on the histopathological changes of the pancreas were observed. Based on these results, it is thought that garlic juice has favorable effects in preventing changes in blood glucose levels, body and pancreas weights, and the histopathological changes in pancreas in STZ-induced diabetes.

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 different energy content in diets. Nine female saanen goats were randomly divided into 3 groups.Animals of all groups were fed either 50%, 100% and 150% energy content in diet for a month.After a month, goats were received 1μg 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 injection of galanin.Blood plasma were assayed for plasma LH and FSH concentrations by RIA. Injection of galanin only in 150% dietary energy intake significantly decreased the mean plasma concentrations of LH and FSH whereas in 50% and 100% dietary energy intake, injection of galanin had no effect on the mean plasma concentrations of LH and FSH. These results indicated that galanin may negatively affects mean plasma concentrations of LH and FSH in the female saanen goats only with positive energy balance.

Acute respiratory disorders such as obstructive pulmonary diseases and hypoventilation may lead to alveolar hypoxia and hypercapnia which their effects on pulmonary vascular beds are controversial. The aim of this study was to establish the isolated perfused lung setup and investigate the effects of alveolar hypoxia and hypercapnia on pulmonary vascular resistance. White New Zealand rabbits anaesthetized and anticoagulated with heparin and trachea cannulated. Then the lung exposed and perfused with Krebs solution through 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 for each). Ventilation performed for 30 min with normoxic-normocapnic, or hypoxic-normocapnic, or hypoxic-hypercapnic gas mixtures. The percent changes of pulmonary vascular resistance per min (%PVR) and their maximum values were evaluated. Hypoxic-normocapnic ventilation resulted in an initial sharp rise in PVR that after 8 min of exposure reversed to a slow decline. 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. In the isolated ventilated perfused lung, acute alveolar hypoxia had a complex influence on PVR and combination of hypoxia with hypercapnia transiently strengthened PVR without affecting its maximum level.

Keratoconus is a relatively common disease of cornea in which structural changes within the cornea cause it to thin and change to a conical shape and scar at the central portion of cornea. So far, few methods and drug treatments were introduced due to both lack of accepted animal models to induce experimental keratoconus and limitation of research in human considering ethical issues. In the present study, keratoconus were produced experimentally in mice focusing on collagen regarding histopathological mechanisms. In this study, collagenase (1, 3 and 6 mg/ml) were injected into the cornea of male mice. Both macroscopic and microscopic evaluations were performed in short periods of one, three and five 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 and stroma changes. Most cornea damage and changes to more conical shape were observed by 6 mg/ml of collagenase. In fact, collagenase at 3 and 6 mg/ml caused deformity and opacity of cornea, dose dependently in a manner that severe damage to collagen fiber, thinness of cornea and epithelium and cornea rupture, in some cases, were observed at high dose of collagenase.

Evaluation of The Acute Hormonal Responses To Concentric, Eccentric And Concentric_ Eccentric Muscle Actions in Healthy Young Men Resistance exercise is a potent stimulus for acute increase in 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 is performed at a external constant load. The aim of this study, is determining hormonal and metabolic response to CON, ECC and CON-ECC muscle actions in order to develop appropriate resistance exercise protocols and equipment for both athletic populations and patients recovering from injury. In the present study, we have examined the endocrine system responses to six different upper and lower body exercise utilizing the CON, ECC and CON_ECC contractions. In this study, we examined acute hormonal responses of GH, TT & FT and cortisol of 10 young men who had experienced resistance exercises nonprofessionally. The exercise protocol included six resistance exercise which three of them were upper body and the other three 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, every exercise was done 10 repetitions per set, and the resting time between exercises and sets was 90 seconds. 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, 15, and 30 minutes after exercise session. In the effect of CON, ECC and CON-ECC contraction actions GH increased, but after CON and CON-ECC trials increased significantly, only. In the effect of three actions, TT & FT increased significantly and following the three actions, cortisol decreased significantly. In despite of existence of significant increase in TT & FT acute response and significant decrease in cortisol response in the effect of CON, ECC and CON-ECC contraction actions, significant difference didn’t observe, that this issue demonstrating that the response of these hormones did not influence by type of contraction action. Also, between acute GH response related to these three actions, observed significant difference that demonstrating GH response depends on type of muscle action and degree of the motor units recruitment besides on intensity and volume of exercise.

To assess the effect of penetration depth of the surface tripolar electrical stimulation, Tripolar TENS was applied with different intensities (equal to sensory threshold (ST), 1.25 ST, 1.5 ST) on vertebral column of twenty healthy and three hemiplegic subjects. The cathode of TENS was laid on the T11 vertebra and anodes were put 3cm apart from cathode, longitudinally and in the anode-cathode-anode arrangement. Before, after and 10 min after TENS the recruitment curve of soleus and gastrocnemius H-reflex and M wave were recorded. Experiments were done in four separate sessions. One of them was control session and the TENS apparatus was off in it. In each of the test sessions, TENS was applied with one of the intensities. The results showed that the 1.5 ST TENS have a complex facilitatory-inhibitory effect on recruitment curve of soleus H-reflex in the way that slow motoneurons were inhibited and fast motoneurons were facilitated. So the positive slope of curve was increased and the intensity needed to evoke Hmax was decreased. Amplitude of Hmax and threshold of the curve were slightly decreased. Gastrocnemius was facilitated after 1.5 ST TENS. 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 ST TENS, soleus was facilitated and gastrocnemius had little change. It seems that 1.5 ST TENS facilitate Ia, Ib, fast motoneurons and renshaw cells via stimulating the dorsal column of the cord and renshaw inhibit slow motoneurons, so a complex of facilitation and inhibition appears in soleus motoneurons. In the case of gastrocnemius which the renshaw cells had not strong effect, H-reflex curve was facilitated. In ST TENS which only the skin afferents were stimulated the renshaw cells were inhibited by skin afferents and H-reflex was facilitated, But because the gastrocnemius motoneurons are slightly under control of renshaw and skin afferents synapses with motoneurons are not engaged in reflex loop, facilitation of skin afferents synapses after TENS application had no effect on the H-reflex parameters of gastrocnemius.