جستجوی مقالات مرتبط با کلیدواژه « گابا » در نشریات گروه « پزشکی »

Menthol is a monoterpene and the main component of essential oils of mint plants family. The sedative and anxiolytic effects of this compound have been reported, previously. However, mechanism of its anxiolytic action has not been elucidated. In this study, the effects of systemic administration of menthol in the open field test and elevated plus maze, also the possible mechanism of its anxiolytic effect in the elevated plus maze were investigated.

In the first phase of this study, mice in 8 separate groups received doses of 5, 10, 20, 50 and 100 mg/kg of menthol, diazepam and buspirone 30 minutes before the behavioral tests to assess anxiety. Based on the results, 50 mg/kg was determined as the effective dose of menthol. In the second stage, flumazenil as a benzodiazepine receptor antagonist and WAY 100635 as a serotonin receptor antagonist were applied to determine the underlying mechanism involved in the anxiolytic effect of menthol.

The present study showed that menthol, especially at the dose of 50 mg/kg, significantly reduced the number of lines, trimming and rearing behavior in the open field test, and increased the number of entries into the open arm and the time spent in the open arm, in the elevated plus maze (p < 0.05). Flumazenil administration reversed these effects in the elevated plus maze, whereas WAY100635 had no effect on it.

Menthol exerts its anxiolytic effects in the mouse elevated plus maze through the benzodiazepine not serotonin pathway.

Glioblastoma multiforme is the most malignant and invasive primary brain tumor in adults. The disease has a poor prognosis with a survival rate of 14-16 months post diagnosis. Depending on the tumor location in the brain, a wide range of signs and symptoms may appear in the patient. One of the most common of which is recurrent hard to control seizures. Despite the high prevalence of tumor-induced seizures, the mechanisms involved in its occurrence are yet to be fully identified. However, it has been shown that glutamate and GABA are probably the major contributing factors. Increasing extracellular glutamate levels due to changes in the expression of ion transporters and the conversion of GABA to a stimulatory mediator are some of the mechanisms involved in the development of these seizures. In addition, factors such as the complex pathophysiology of the disease, its associated-seizures, drug interactions, resistance to treatment and tumor recurrence have made glioblastoma management a major challenge. In this article, the common clinical symptoms of this disease and in particular tumor-associated seizures are reviewed. The mechanisms thought to be responsible for the development of the tumor-induced seizures are then discussed.

Previous studies have shown the protective effect of cyclooxygenase (COX) enzyme in development of convulsions. However, involvement of COX-2 in the pathogenesis of epilepsy is not yet well-known. The present study was designed to investigate the effect of celecoxib and nimesulide (selective COX-2 inhibitors) on pentylenetetrazole (PTZ)-induced clonic seizure threshold in mice.
In this study, white male mice were randomly divided into 13 groups including control groups, solvent (Tween 80) and eleven experimental groups which received celecoxib (2.5, 5 and 10 mg/kg), nimesulide (2.5, 5 and 10 mg/kg), diazepam (0.1, 0.5 and 5 mg/kg), and combination of non-effective dose of diazepam with celecoxib or nimesulide. Pentylenetetrazol-induced clonic seizure threshold was assessed in all groups.
Nimesulide (2.5 and 5 mg/kg), celecoxib (2.5 and 5 mg/kg), and diazepam (0.5 and 5 mg/kg) significantly increased the PTZ-induced seizure threshold compared with the solvent group (P Findings of the current study show the possible role of COX-2 isoenzyme in the pathophysiology of epilepsy. It is possible that some COX-2 inhibitors such as celecoxib act through GABAergic neurons and reduce excitability by increasing GABA release. Also, the difference between the effects of celecoxib and nimesulide can be attributed to the effect of these two compounds on COX-1 and COX-2 expression.

As a psychoactive plant, Cannabis sativa (Marijuana) is widely used throughout the world. Several investigations have indicated that administration of Marijuana affects various cognitive and non-cognitive behaviors. These include anxiety-like behaviors and learning and memory deficit. It has been shown that three main cannabinoid receptors [i.e. CB1, CB2 and CB3 are involved in cannabinoids’ functions. CB1 receptors are abundantly expressed in the central nervous system regions such as hippocampus, amygdala, cerebellum and the cortex. Therefore, the neuropsychological functions of endocannabinoids are thought to be more linked to CB1 receptors. Among other brain regions, CB1 is highly expressed in the amygdala which is an integral component of the limbic circuitry. The amygdala plays a major role in the control of emotional behavior, including conditioned fear and anxiety. In present study we examined the possible roles of basolateral amygdala (BLA) GABAB receptors in arachydonilcyclopropylamide (ACPA)-induced anxiolytic-like effect and aversive memory deficit in adult male mice.
This experimental study was conducted from September 2013 to December 2014 in Institute for Studies in Theoretical Physics and Mathematics, School of Cognitive Sciences, Tehran and Male albino NMRI mice (Pasture Institute, Iran), weighting 27-30 g, were used. Bilateral guide-cannulae were implanted to allow intra BLA microinjection of the drugs. We used Elevated Plus Maze (EPM) to examine memory and anxiety behavior (test-retest protocol). ACPA administrate intra-peritoneal and GABAB agonist and antagonist administrated intra-amygdala.
Data showed that pre-test treatment with ACPA induced anxiolytic-like and aversive memory deficit The results revealed that pre-test intra-BLA infusion of baclofen (GABAB receptor agonist) impaired the aversive memory while phaclofen (GABAB receptor antagonist) improved it. Interestingly, pretreatment with a sub-threshold dose of baclofen reversed and potentiated anxiolytic-like effect and aversive memory deficit induced by ACPA, respectively. Conversely, similar effect with sub-threshold dose of phaclofen showed that this drug only restored aversive memory deficit but did not alter anxiolytic-like effect induced by ACPA.
Data indicated that BLA GABAB receptors have critical and different roles in anxiolytic-like effect and aversive memory deficit induced by ACPA.

Seizure is an abnormal electrical activity probably due to an imbalance between excitation and inhibition in the brain. Pentylenetetrazol (PTZ) is a chemical convulsive agent abundantly used in laboratory animals. PTZ induces a change in glutamate and GABA in the brain which this study investigates the persistence of this change. In this experimental study, 18 male Wistar rats divided into 3 groups. Three i.v doses of PTZ; 20, 25 and 30 mg/ml were used to determine the effective PTZ dose. Convulsive behaviors were monitored as tonic clonic and myoclonic twitches. Hippocampal glutamate and GABA contents were measured using a biochemical method. Dose of 20 was resulted in long latency to and short lasting TC convulsions with a high volume of injected PTZ solution. On the other hand, dose of 25 and 30 led to short latency and long lasting convulsions with low volume of injecting solution. However there was high rate of mortality (100%) in dose of 30 mg/ml. Hippocampal glutamate content was decreased in zero and 20 min groups while GABA content was decreased only in 20 min group. It is concluded that dose of 25 is the appropriate i.v dose to induce TC convulsions in rats which decreases glutamate and GABA while increases the ratio of glutamate to GABA. Therefore, alteration of glutamate and GABA may be the basis for subsequent seizure induced changes.

GABAergic system in ventral tegmental area (VTA) and nucleus accumbens (NAc) plays critical role in opiate reinforcement. On the other hand, vitamin B6 has a role in formation of different neurotransmitters such as GABA. The aim of this study was to investigate the effect of intraperitoneal (ip) and intracerebroventricular (icv) injection of vitamin B6 on positive reinforcing effect of morphine in male rat. Ninety male rats were divided into treatment and control groups (15×6). This experimental study took place on six consecutive days, which consisted of three distinct phases: preconditioning, conditioning and postconditioning. For intracerebroventricular study, a sterile guide cannula was stereotaxically placed in left ventricle. After conditioning by morphine (5mg/kg, ip), on day 6 different doses of vitamin B6 were injected intrapertioneally (5, 15 and 40 mg/kg) and intracerebroventriculary (5 and 10µg/rat). Control groups received saline instead these drugs. Intraperitoneal injection (ip) of different doses of morphine induced CPP (P<0.001). Intraperitoneal injection of different doses of vitamin B6 alone did not induce any significant CPP or CPA. But, co-administration of vitamin B6 and morphine, significantly induced CPA (P<0.05) and this effect potentiated in icv injection in dose dependent maneuver manner (P<0.05 and P<0.01, respectively). It seems that vitamin B6 reduce morphine reinforcement through affecting GABAergic VTA neurons and subsequent decrease in NAc dopamine release. Therefore, it can be candidate for control or treatment of morphine craving and relapse in their dependent subjects.

The nucleus bed of the stria terminalis (BST) is a part of the limbic system. Previous studies have shown that inhibition of GABA A receptor increases blood pressure and heart rate. This study was performed to find the possible mechanisms and circuits that mediate these responses. In 39 urethane-anesthetized male rats the femoral artery and vein were cannulated for recording the blood pressure and heart rate and drug injection respectively. Trachea was cannulated to ease ventilation, and bicuculline was unilaterally microinjected into the BST using micropipette. The maximum changes of mean arterial pressure (MAP) heart rate (HR) were compared with the preinjection values using the paired t-test. Injection of bicuculline methiodide (BMI, 100 pmol/100 nl), a GABAA antagonist, caused a significant increase in the MAP (41.3±5.1 mmHg) as well as in the HR (33.2±5.6 beats/min). Administration (i.v.) of the muscarinic receptor blocker, homatropine methyl bromide had no effect on the magnitude of mean arterial pressure or heart rate responses to BMI, suggesting that the parasympathetic system is not involved in these responses. However administration (i.v.) of the nicotinic receptor blocker, hexamethonium bromide, althought it had no effect on the magnitude of mean arterial pressure response, did abolish heart rate response to BMI, indicating that the sympathetic system is involved in the bradycardic effect of GABA. On the other hand, administration (i.v.) of a selective vasopressin V1 receptor antagonist abolished the pressor effect of BMI, which suggests that the GABAergic system of the BST decreases the arterial pressure via tonic inhibition of vasopressin release. We demonstrated, for the first time, that inhibition of GABAA, receptors increase blood pressure and heart rate via tonically inhibiting vasopressin release and sympathetic outflow to the heart.

In female rats sensitivity to antinociceptive treatment varies during estrous cycle stages. The role of GABA through GABAB receptor in nociception has been established. The aim of the present study is to investigate the effect of intercerebroventicular injection of GABAB receptor agonist (baclofen) and GABAB antagonist (CGP35348) on pain sensitivity during different stages of estrous cycle. Forty adult female rats weighing 200-220g were used. Rats were maintained on 12 h reversed light/dark cycle, and standard temperature 22 ± 2°C. Food and water were available ad libitum. Pain sensitivity was evaluated by formalin test, performing by subcutaneous injection of 50µl formalin solution (2.5%) into the hind paw in each stages of estrous cycle. Data were analyzed by two ways ANOVA measuring and Tucky test as post-hoc test. The level of significance was P<0.05. Our data showed that baclofen significantly decreased pain sensitivity in all stages of estrous cycle (P<0.05). The analgesic effect of baclofen was significantly higher during metestruse and diestruse as compared to proestruse and estrus (P<0.05). CGP35348 significantly increased pain sensitivity in all stages of estrous cycle (P<0.05). The hyperalgesic effect of CGP35348 was significantly lower during metestruse and diestruse than proestruse and estrus (P<0.05). Administration of baclofen in pretreated rats with CGP35348 did not induce any significant change in pain sensitivity (P>0.05). We have demonstrated that GABA through GABAB receptor can modulate pain sensitivity during estrous cycle.

Following the seizure there is an inhibitory period named “post-ictal depression period” which has a depressing effect on the following seizure. In this study, the role of GABAA receptors on post-ictal depression period was investigated in amygdala kindling model of epilepsy in rat. Animals were kindled by electrical stimulation of amygdala. Then, they were divided into four groups. Different groups of kindled animals were received a second stimulation at 10, 30, 60 and 90 min after the first stimulation and the percentage of suppression of seizure parameters after the second stimulation was calculated. In another four groups, bicucullin, a selective GABAA receptor antagonist (100 nM), was intra-cerebroventricularly microinjected 10 min before the second stimulation and its effect on the percentage of suppression induced by the first stimulation was investigated. Six animals were used in each group. When the second stimulation was applied at 10 and 30 min after the first stimulation a significant reduction was observed in the seizure severity and seizure parameters were depressed after the second stimulation. Bicucullin microinjection significantly decreased the percentage of depression in seizure parameters following the second stimulation compared to the animals received the solvent alone (P<0.05). This decrease was significant when the second stimulation was applied at 10 and 30 min after the first stimulation. Obtained results showed that activity of GABAA receptors by endogenous GABA is one of the mechanisms involved in post-ictal depressing period. However, the blocking of these receptors could not completely prevent this period. Thus, other factors have also role in its induction

Type I diabetes is an autoimmune disease associated with T lymphocytes function in beta cells. This process can increase cytokine secretion, which can cause beta cell inflammation and death. Since GABA, (γ-aminobutyric acid) is a major inhibitory neurotransmitter, and low concentration of GABA can increase cytokine secretion, the aim of this study was demonstrate to the inhibitory effect of GABA administration on cytokine secretion and decrease in beta cell death and also to show the ability of beta cells in insulin secretion. Seven week old CD1 mice were used. To induce diabetes, animals received 40 mg/kg of STZ five days continuously. Two months later, animals were divided into two groups, one receiving 200 micromole of GABA and the other (controls) the same volume of PBS for 10 weeks. Serum glucagon levels, and alpha cells significantly decreased in the (IL12 IL1β, TNFα) mass and some cytokine levels in the GABA group. Plasma insulin level and beta cell mass significantly increased in comparison to the control group. From the results of this study we conclude that GABA administration causes inhibition in cytokine secretion, improves beta cell mass and increases insulin secretion. May be, in the future, if GABA shows no side effects we can use GABA for type one diabetes.

The Rostral Ventromedial Medulla (RVMM) is one of the nuclei controlling cardiovascular system. This study was performed to delermine the effects of 17β-estradiol (E), on the GABA and Glutamate cardiovascular responses of RVMM of female rats Experiments were performed on 40 anaesthetized and paralyzed rats, divided into two groups of ovarictomized (OVX) and ovarictomized-estrogen treated (OVX+E) rats. Drugs (50 nl) bicuculline methiodide (BMI) an antagonist GABAA receptor (1 mM), phaclophen an antagonist GABAB receptor (5mM), and kynurenic acid a nonselective antagonist glutamate receptors (5 mM), were microinjected by micropipette into the RVMM using stereotaxic system. Blood pressure and heart rate were recorded before and throughout each experiment. The means of maximum changes of mean arterial pressure and heart rate were compared between groups of OVX and OVX+E and saline using ANOVA. In the OVX+E group, estrogen decreased the mean arterial blood pressure (P<0.05) and heart rate (P<0.001) compared to those of OVX group. Microinjection of BMI resulted in an increase of heart rate (HR) with no significant effect on the blood pressure (BP) in both OVX and OVX+E, but the increase of HR was significantly higher than in the OVX+E group (p<0.05). Microinjection of phaclophen and kynurenic acid had no significant effect on HR and BP in either the OVX or the OVX+E group not did microinjection of saline have any significant effects on HR and BP. The present data suggest that estrogen decreased the mean arterial blood pressure and heart rate, and in the RVMM of female rats augments the inhibitory effect of the GABAergic system on the heart rate via the GABAA receptors.

Parathion is an organophosphate compound that is frequently used as an insecticide. Paraoxon is the metabolic product of parathion which previously reported that inhibits GABA uptake by rat cerebral cortex synaptosomes. The aim of this study is to investigate possible underlying inhibitory mechanism(s) of paraoxon on GABA uptake, in synaptosomes prepared from rat cerebral cortex. After preparation of synaptosomes, kinetic studies were performed to determe the effect of paraoxon on Km and Vmax of GABA uptake. Acetylcholine and its antagonists (atropine and mecamylamine) were used to evaluate cholinergic dependency of GABA uptake. Type of GABA transporter involved was determined using beta-alanine and DABA. The results of the study showed that paraoxon significantly decreased Vmax (175.2±4.23 vs. 80.4±2.03 pmol/mg protein/min, P<0.001) of GABA uptake while had no effect on its km (9.80±1.02 vs. 9.09±0.92μM in paraoxon and control groups respectively). DABA significantly decreased GABA uptake (P<0.001) while beta-alanine had no effect. Acetylcholine had no effect on GABA uptake. On the other hand, neither atropine nor mecamylamine could reverse the inhibitory effect of paraoxon on GABA uptake. In conclusion, it seems that paraoxon acts as non-competitive anatagonist of GABA uptake, which affects kinetics of GABA uptake in nerve endings. We also conclude that the inhibitory effect of paraoxon on GABA uptake is cholinergic-independent

Gamma-amino butyric acid (GABA), an amino acid, present in some inhibitory neurons of the central nervous system, is also found in relatively high levels in the islets of Langerhans. Results of different studies concerning the effect of GABA on insulin secretion are controversial. The aim of this study was to determine the role of GABA and GABAB receptors on glucose-stimulated insulin secretion in isolated islets of rats. The collagenase digestion technique was used to isolate the islets from pancreata of 45 male Wistar rats (200-250g). Insulin secretion was assessed in eight islets in each cup exposed to different concentrations of glucose (8.3 and 16.7 mM) in the presence or absence of GABA(25, 50, 100 µM), baclofen (10, 20, 50 µM) (GABAB agonist) and saclofen (50,100 µM) (GABAB antagonist). Insulin concentration was measured by the ELISA method. Insulin release was reported as mean±SEM U/islet/50min and p values of <0.05 were considered significant. GABA inhibited glucose (8.3 and 16.7 mM)-induced insulin secretion in isolated islets (P<0.05). Different concentrations of baclofen had no significant effect on glucose-induced insulin secretion however glucose (16.7mM) stimulated insulin secretion in the presence of 100 µM saclofen (91±8.8 µU/islet/60min) was significantly (p<0.05) higher compared to insulin secretion stimulated by 16.7mM glucose alone (67.7±2.58 µU/islet/60min). These findings indicate that GABA has an inhibitory effect on glucose-induced insulin secretion and therefore it may play a regulatory role in insulin secretion. This effect needs to be taken in to account in the pathophysiology of diabetes.

γ-aminobutyricacid (GABA), a major neurotransmitter in the central nervous system, also acts as a paracrine or autocrine signaling molecule in endocrine tissues such as the pancreatic islets, adenohypophysis, and testis. It has been demonstrated that metabolites of progesterone and corticosterone naturally act via the GABAA – membrane receptor and they have sedative–hypnotic, anxiolytic, anticonvulsant, muscle-relaxant and anesthetic drugs properties. Also the brain as a steroidogenic organ contributes to produce these steroids. The aim of this study was to find out the steroids participation on the GABA- related activities. An injection canula was inserted into lateral ventricle of the sham and experimental adult female rats by stereotaxic surgery. One week late, at proesterus day, diazepam (GABAA–receptor agonist) with doses of 250 and 500ng/rat, bicuculine (GABAA–receptor antagonist) with doses of 1.5 and 3 ng/rat, baclofen (GABAB –receptor agonist) with doses of 4.27 and 8.54 ng/rat and CGP35348 (GABAB –receptor antagonist) with doses of 3 and 5 µg/rat were intracerebroventriculary (ICV) injected to the experimental groups, while equal volume (2µl) of artificial CSF was injected to the sham operated group. Blood samples were collected thrice at 9 AM, 11 AM and 1PM. The serum progesterone level was determined using RIA method. Data were analyzed by one way ANOVA and Duncan's test at p<0.05 for the significant level. The results showed that GABAergic system activity via both GABAA and GABAB receptors has significantly changed the serum progesterone level. Comparing the results of this research with earlier studies, it is concluded that GABAergic system has a close relation with steroidogenesis and the steroids participate in GABA-related activities