Physiology and Pharmacology
Year:2008 | Volume:11 | Issue:4|Papers Count:13

Introduction: Barrel cortex of rats is a part of somatosensory cortex, which receives information from facial whiskers. Vibrisectomy by sensory deprivation leads to changes in the barrel cortex, which is known as experience dependent plasticity. On the other hand, Norepinephrine (NE) and locus coeruleus as the main source of NE, modulate response properties of cortical barrel neurons. In this study, the effect of NE depleted and sensory deprivation on induction of experience dependent plasticity was investigated.Methods: In this study sixty Wistar rats (250±25g) were used. Rats were divided into four groups: 1. Control group 2. NE depleted group (Norepinephrine was selectively depleted by IP injection of DSP4). 3. Sensory deprivation group (all whiskers except the whisker D2 on the left side were trimmed every other day). 4. NE depleted + sensory deprivation group. Excitatory (magnitude and latency) and inhibitatory (Conditioning Test Ratio, CTR index) receptive fields of barrel cortical neurons were assessed Using extracellular single unit recordings.Results: Sensory deprivation led to an increase both in the magnitude of response to principle whisker deflection (spared whisker) and in the CTR. In NE depleted+sensory deprivation group, the response magnitude and CTR index were the same as control group.Conclusion: The result showed that experience dependent plasticity has a facilitating effect on excitatory receptive field while decreasing the inhibitory circuits in the brain. When NE content of the brain was depleted before sensory deprivation, these changes were not seen. We conclude that NE depletion inhibits the plastic changes in the response properties of neurons following sensory deprivation.

Introduction: There are evidences showing the role of nitric oxide in the opiate reward properties. The role of nitric oxide signaling pathway as an intracellular mechanism on augmentation of long term potentiation in hippocampal CA1 area of rats is also confirmed. It has been also reported that oral morphine dependence facilitates formation of spatial learning and memory via activation of NMDA receptors located in hippocampal CA1 area of rats. The effect of nitric oxide within hippocampal CA1 area on the spatial learning and memory processes in morphine dependent rats is unclear.Methods: 33 N-MRI male rats (250-350 g) were divided into 4 experimental groups. Two cannulae were stereotaxically implanted bilaterally into 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 this period animals received bilateral intra-hippocampal CA1 injection of 3mg/ 2ml L-NAME (NOS inhibitor) or 2ml saline (1ml/site), 1 min before daily experimentation. Spatial learning and memory parameters were subjected to analysis of variance (ANOVA).Results: Morphine dependence facilitated spatial learning and memory in rats. This effect was inhibited with local administration of L-NAME in hippocampal CA1 area.Conclusion: Activation of intracellular NO signaling pathway in the pyramidal cells of hippocampal CA1 area may involve in facilitating spatial learning and memory in morphine dependent rats.

Introduction: Ouabaine is a well-known atrioventricular (AV) node depressant agent, but its effects on functional properties of the AV node have not been cleared. The aim of the present study was to determine how ouabaine administration modifies the rate-dependent properties of the AV node.Methods: Selective stimulation protocols were used to quantify independently electrophysiological properties of the Node. Ouabaine was added directly to superfusion tyrods in a cumulative model (0.05, 0.1, 0.2, 0.25 mM). The same stimulation protocols were repeated before and after ouabaine addition. Comparisons among multiple groups were made by two-way analysis of variance. P<0.05 was considered significant.Results: Ouabaine decreased fatigue in low concentration (0.05mM), whereas at high concentrations increased the magnitude of fatigue. Ouabaine (0.2, 0.25 mM) caused significant increase in basic properties of the AV-Node (AVCT, WBCL, ERP, FRP). WBCL was prolonged by ouabaine (0.25mM) from 147.5±8.9 to 194±13 msec. Also amount of facilitating decreased by 0.2mM ouabaine from 43.3±5 to 38.8±5 msec.Conclusion: The paradoxical effects of ouabaine on the fatigue indicate potential role of Na+-K+-ATPase in the protective mechanism of the AV-node.

Introduction: Endothelium and smooth muscle dysfunction are the most important complications of diabetes. In type 1 diabetic patients, absence of insulin leads to vasoconstriction and lower skin blood perfusion. Release of some mediators by endothelium which is induced by insulin causes vasodilation, but the exact mechanism of insulin vasodilatory effect is not detected properly. At present study we investigated the role of NO as a vasodilator and KATP channels and their interaction in the vasodilatory effect of insulin on the skin vessels.Methods: Male Wistar rats (200-250 g) were made diabetic by streptozocin (50 mg/kg, s.c). After 40 days of diabetes induction, skin blood flow was measured by Laser Doppler Flowmetry (LDF) technique. Insulin, LNNA (NO blocker) and Glibenclamide (KATP blocker) infusion were subcutaneously made by infusion pump. Results: Insulin increased skin blood flow in both control and diabetic groups and this increase was significantly higher in diabetic group. Insulin vasodilatory effect was decreased by LNNA and Glibenclamide. Simultaneous block of both NO and KATP was more effective.Conclusion: Insulin induces vasodilation in part by NO release and partly by activation of K ATP channels. However some interaction has been reported between these two pathways. Since by block of these routes blood flow has not been completely inhibited, other factors may be involved in this effect and yet to be elucidated.

Introduction: Peripheral nerve injury leads to neuropathic pain syndromes and different sensation like allodynia and hyperalgesia. Different animal models of neuropathic pain are used to study the neuropathic pain mechanisms. The present study was performed on two models, (SNI). The purpose of this study was comparing the behavioral responses of yhese two models and the role of saphenous and sural nerve in SNI model. Methods: Male Wistar rats (180-220 g) were used. CCI models were made by 4 loose legations on common sciatic nerve. In SNI models, 2 of 3 terminal branches of sciatic nerve were cut and the sural nerve was remained intact. Zero, 4, 7 and 14 days after the operation, thermal hyperalgesia and mechano allodynia were assessed with radiant heat with von-frey filament.Results: The results indicated mechano allodynia and thermal hyperalgesia at days 4th, 7th and 14th. In comparison of SNI and CCI, there was no significant difference in pain behaviors; however there was more sensitivity to allodynia in the SNI model and more sensitivity to hyperalgesia in the CCI model. Saphenous territory showed less allodynia and hyperalgesia than sural territory.Conclusion: behavioral testes of CCI and SNI models demonstrated the hypersensitivity to both thermal and mechanical stimuli. But there were different pain intensity between the sural and saphenous nerve territories in SNI model. It seems different neuropathy models have different mechanisms and symptoms.

Introduction: Previous studies have indicated that stress levels of glucocorticoid hormones induce impairment of long term memory retrieval, but the underlying mechanisms (genomic or non-genomic) are not clear. To clarify this issue, we investigated the involvement of brain corticosteroid receptors and protein synthesis in the glucocorticoid-induced impairment of memory retrieval.Methods: 140 young rats were trained in the water maze (WM) task with six trials per day for six consecutive days. Retention of the spatial training was assessed 24 h after the last training session with a 60-s probe trial. Experiments included intraventricular injections of anisomycin (187.5 or 450mg/5ml), a specific protein synthesis inhibitor or specific antagonists for mineralocorticoid receptors (MR, 37.5, 75, 150 mg/5ml) or glucocorticoids receptors (GR, 75 or 150mg/5ul) before corticosterone administration (1 mg/kg) shortly before retention testing.Results: The results showed that administration of anisomycin did not change the corticosterone response. Administration of the MR, but not GR, antagonist blocked the corticosterone-induced response.Conclusion: These findings provide evidence for the view that glucocorticoids impair memory retrieval through non-genomic mechanisms involving an interaction with central MRs.

Introduction: The effect of morphine dependency on learning and spatial memory is controversial. In this study, the effect of co-administration of nitric oxide (NO) and morphine in CA3 region of hippocampus on learning and spatial memory in morphine dependent rats was investigated.Methods: After anaesthetizing of male rats, guide cannula was implanted bilaterally in CA3 region of hippocampus. After recovery period (7 days), morphine dependency was induced then animals divided to 6 groups and respectively received 1ml saline, L-Arginine, L-Name, morphine, L-Arginine+morphine and/or L-Name+morphine. Morphine dependency was induced by subcutaneous injections of morphine (10 mg/kg first day and 20 mg/kg for four next days). During Morris water maze test period, last dose of morphine (20 mg/kg) was injected daily to maintain morphine dependency.Results: L-Name decreased learning in morphine dependent rats but it was not effective on retention of memory. Morphine did not affect learning and spatial memory. Co-administration of L-Arginine and morphine promoted the effect of L-Arginine on learning and spatial memory.Conclusion: It seems that comparing to separate administration, co-administration of NO and morphine in morphine dependent rats does a better improvement in learning and spatial memory.

Introduction: Traditionally, Peganum harmala seeds (P.h) have been extensively used in the Asia region. We have previously reported the increase of fear behavior by systemic administration of P.h extract. Here, we evaluated the effect of central administration of the extract on the fear behavior.Method: Methanolic extract of the plant's seeds (37% humidity) was prepared for the investigation. Elevated plusmaze apparatus was used for evaluating the fear behavior. Adult male rats were categorized in 7 main groups (n=6). 1) Sham control (saline 1 ul/rat, i.c.v) 2) Harmaline treated group (50 ug/rat, i.c.v). 3) Extract treated groups (10, 20, 25, 50, 100 ug/rat i.c.v respectively).Results: All the doses of the P.h Methanolic extract as like as harmaline caused fear behavior (p<0.05). There was no significant difference between the effects of harmaline and the doses of the plant extract.Discussion: Overall, it is possible that the main alkaloid of the P.h (harmaline) is responsible for the increasing of fear behavior. The effect seems to be done trough the central nervous system neurochemical mechanisms.

Introduction: Ischemic-reperfusion nerve injury has been suggested as the mechanism for post-tourniquet limb paralysis. Dexamethasone (Dex) has been known to prevent ischemic-reperfusion side effects in some tissues, we here evaluated its possible preventing effect on tourniquet induced nerve injury.Methods: 36 male Wistar rats (200-250 g) were divided randomly into 6 equal groups named as Sham Operated, Vehicle, Control and treatments (Dex1, Dex2 and Dex3). Tourniquet was applied to the right hind limb of all Animals except of Sham and Vehicle groups for 3 hours. Animals of Control and Vehicle groups were received 1 ml of vehicle (Normal saline containing 4% ethanol). Animals of Dex1, Dex2 and Dex3 groups were respectively received 1 mg/kg, 2 mg/kg and 3 mg/kg of Dex 30 min before fastening tourniquet, 30 min after releasing tourniquet and daily during the week of experiment. Motor nerve conduction velocity (MNCV) of tibial nerve in response to nerve stimulation was measured one week after releasing the tourniquet.Results: Application of the tourniquet for 3 h significantly decreased MNCV in all animals (p<0.001). Dexamethasone administration in doses of 2 and 3 mg/kg (Dex2 and Dex3 groups) resulted in a significant improvement of MNCV (p<0.001) in comparison to control group.Conclusion: These data indicated that dexamethasone administration in doses of 2mg/kg and 3mg/kg could prevent nerve conduction velocity loss in tourniquet neuropathic rat.

Introduction: The claustrum interconnects with different regions and also projects to the hippocampus and the amygdala. The role of claustrum in the complex partial seizure is not clear. In the current study, the effect of amygdale lesion on anterior claustrum kindled seizures in rat was investigated.Methods: Male Wistar rats, weighting 250-300 g, were received DC current via a bipolar electrode inserted in right basolateral amygdala. A tripolar electrode for stimulation and electroencephalography recording in the right anterior claustrum has been fixed. After a 10 days period of recovery, animals were daily received kindling stimulation (60 Hz, for 2s, with 1 ms pulse duration) and kindling parameters were measured. Control animals did not receive the DC current. Two lesion groups respectively received DC current before kindling stimulations and after full kindled statement achievement.Results: Our results showed that amygdala lesion, was capable of delaying claustrum kindling with increasing the stimulation trials required to kindle to seizure stages. Furthermore the lesion reduced the severity of established kindled seizures by decreasing the stage 5 duration and after discharge durations.Conclusion: Amygdala lesion had no effect on the expression of generalized seizures and claustrum play an important role in the propagation of epileptic seizure. Whereas the amygdala has a facilitators role in propagation claustrum kindled seizure.

Introduction: It is well established that thyroid hormones are essential for normal development of mammalian brain. Thyroid hormone deficiency during critical period of brain development can exert devastative and irreversible effects on neuronal functions as well as on learning abilities and memory. The aim of the present investigation was to investigate the effects of maternal hypothyroidism on the neuronal structures of the subiculum in an experimental model of cretinism.Methods: Twenty five female Wistar rats were divided into experimental groups 1 and 2 and control. The experimental groups were made hypothyroid (500 mg/L PTU in drinking water). The experimental group 2 received PTU+Levothyroxin (1mg/L in drinking water). The controls only received drinking water. After two weeks the animals were mated. During pregnancy and lactation, the treatment regime of all groups was continued as above. The brain of 20 days old newborns were dissected and fixed for histological preparation. The numerical density (NV) of subicular neurons was estimated by applying a stereological technique "dissector". Results: In addition to the effects of maternal hypothyroidism on the litter size and offspring weights, the results showed significant increase of subicular neuronal density in experimental group 1 when compared with control (p<0.001). There was also a significant difference (p<0.001) between the Nv of experimental groups 1 and 2. Conclusion: The increased of neuronal Nv in hypothyroid rats was probably due to the retardation of the neuronal normal growth and extension of their dendritic arborization. It seems that thyroxin therapy can improve the effects of hypothyroidism on the neuronal structure of subiculum.