Enhancement of pentobarbital-induced sleep by apigenin through chloride ion channel activation

This experiment was performed to investigate whether apigenin has hypnotic effects and/or enhances pentobarbital-induced sleep behaviors through the GABAergic systems. Apigenin prolonged sleep time induced by pentobarbital similar to muscimol, a GABA(A) receptors agonist. Apigenin also increased sleep rate and sleep time in the combined administration with pentobarbital at the sub-hypnotic dosage, and showed synergic effects with muscimol in potentiating sleep onset and enhancing sleep time induced by pentobarbital. In addition, both of apigeinin and pentobarbital increased chloride influx in primary cultured cerebellar granule cells. Apigenin increased glutamate decarboxylase (GAD) and had no effect on the expression of GABA(A) receptor α-, β-, γ-subunits in n hippocampus of mouse brain, showing different expression of subunits from pentobarbital treatment group. In conclusion, it is suggested that apigenin augments pentobarbital-induced sleep behaviors through chloride ion channel activation.     

Effect of alkylpyrazine derivatives on the duration of pentobarbital-induced sleep, picrotoxicin-induced convulsion and gamma-aminobutyric acid (GABA) levels in the mouse brain

The effect of alkylpyrazine derivatives on pentobarbital-induced sleeping time, picrotoxicin-induced convulsion and gamma-aminobutyric acid (GABA) levels in mouse brain were studied. The duration of pentobarbital-induced sleep in mice was dose-dependently increased by 2,5-dimethylpyrazine (DMP). The duration of pentobarbital-induced sleep was also increased by an administration route of intracerebroventricular injection. Sleep duration was also increased by the administration of isomers of DMP, 2-chloro-3,6-dimethylpyrazine (DMP-Cl) and 2-fluoro-3,6-dimethylpyrazine (DMP-F), but 3,6-dimethylpyrazine-2-thiol (DMP-SH) did not affect sleep duration. The interval until the appearance of picrotoxicin-induced convulsion was prolonged by DMP and DMP-Cl. Increased sleep duration was obtained by administering DMP in combination with aminooxyacetic acid (AOAA) and diazepam compared to a single injection. The interval until convulsion due to picrotoxin was also prolonged by the administration of DMP combined with diazepam and valproic acid (VPA). The interval until the appearance of bicuculline-induced convulsion was also prolonged by pretreatment with DMP. The GABA level in mouse brain was increased by the administration of AOAA, VPA, DMP and DMP-Cl. These results suggest that DMP and other derivatives may strengthen the GABAnergic system in the brain.     

Interaction of doxapram and pentobarbital in mice

We found a statistically significant increase in duration of pentobarbital-induced narcosis in doxapram-treated mice. The influence of doxapram (a respiratory stimulant) pretreatment on pentobarbital metabolism in mice was assessed by measurements of sleeping times, hypothermia, LD50 values, hepatic microsomal metabolism and relative plasma and brain levels of pentobarbital. When doxapram was given intraperitoneally 60 min. prior to administration of pentobarbital, doxapram potentiated pentobarbital-induced narcosis in a dose- and time-dependent manner, but had no effect on onset time. Doxapram potentiated hypothermia, increased acute toxicity, and prolonged the pentobarbital half-life in brain and plasma, but measurement of the concentration of pentobarbital in the brain and plasma immediately upon recovery from narcosis showed that there were no differences in any of the groups examined. Also, brain-to-plasma ratios of pentobarbital did not differ between the control and doxapram-treated groups. Doxapram competitively inhibited the hepatic metabolism of pentobarbital in 9000 x g supernatant incubation mixtures. The results obtained from these experiments indicate that inhibition of drug-metabolizing enzymes by doxapram may account for its enhancement of the duration of pentobarbital-induced narcosis.     

Effect of aminooxyacetic acid, thiosemicarbazide and haloperidol on the metabolism and half-lives of glutamate and GABA in rat brain

The activity of the enzymes glutamate decarboxylase (GAD) and GABA-2-oxoglutarate transaminase (GABA-T), the endogenous GABA and glutamate levels and the half-lives ($\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ values) of radioactive GABA and glutamate have been measured in the brains of untreated rats and in those injected with aminooxyacetic acid (AOAA), thiosemicarbazide (TSC) and haloperidol. The effect of the drugs in vitro on a purified preparation of glutamate dehydrogenase (GDH) was also measured.AOAA profoundly inhibited GABA-T, did not inhibit GAD and in in vitro experiments activated GDH. Brain glutamate levels were unaffected by the drug as was the half-life for glutamate. Brain GABA levels were elevated after AOAA and the rate of disappearance of radioactive GABA slowed.TSC did not significantly alter either GABA or glutamate brain levels but did significantly inhibit GAD and GDH activities. In addition, TSC had no effect on the half-life of either GABA or glutamate.Haloperidol was an effective inhibitor of GDH in vitro and reduced brain glutamate concentrations in vivo. Moreover, the rate of disappearance of radioactive GABA was increased whereas that of glutamate was decreased. The drug had no effect on GAD and GABA-T activities or on brain levels of GABA.It is suggested that the behavioural effects of haloperidol might in part be due to actions on the metabolism of GABA and glutamate. Interaction of TSC with glutamate metabolism might be a factor in seizure-provoking activity of the drug.     

Changes in γ-aminobutyric acid and glutamic acid decarboxylase in discrete regions of rat brain following lithium administration and withdrawal

The influence of low dose (1 mmol/kg/day) chronic lithium (Li) treatment was studied on γ-aminobutyric acid (GABA) levels and glutamic acid decarboxylase (GAD) activity in discrete regions of rat brain. In Li-treated animals, GABA levels of striatum, midbrain, and ponsmedulla were significantly elevated in comparison to controls. Following 2 days of withdrawal from Li, GABA remained significantly higher in midbrain and pons-medulla, but returned to control values in striatum. Administration of aminooxyacetic acid (AOAA) 1 hr prior to sacrifice produced an approximately twofold increase in regional GABA content in all three experimental groups. The activity of GAD was enhanced in striatum (11%) and pons-medulla (22%), but decreased slightly in midbrain (5%) of Li-treated animals. Li withdrawal caused a significant reduction in GAD activity of hypothalamus and pons-medulla when compared to control or Li-treated rats. Acute injection of AOAA enhanced GAD activity in midbrain of the Li-treated animals and hypothalamus of the Li-withdrawal group. Our data demonstrate that long-term Li administration and its subsequent withdrawal has differential effects on both GABA and GAD in various regions of rat brain. However, whether these changes brought about by Li are due to its direct effect, or are exerted indirectly through other neurotransmitter systems, needs to be clarified.     

Aminooxyacetic acid: correlation between biochemical effects, anticonvulsant action and toxicity in mice

The time courses of changes in brain content of γ-aminobutyric acid (GABA) and sensitivity to convulsions were studied in mice after administration of aminooxyacetic acid (AOAA) (30 mg/kg, s.c.). There was a good correlation of increase in GABA content with elevation of the thresholds for the electroconvulsion as well as for the pentetrazole convulsion, the maximal effect being after 6hr. The activity of GABA-α-oxoglutarate aminotransferase (GABA-T) was reduced to near zero within 30 min of administration of AOAA, whereas the activity of glutamate decarboxylase (GAD) was not influenced in vivo. However, AOAA had a pronounced inhibitory effect on both enzymes in vitro. Based on the results of the threshold determinations, the anticonvulsant effect of AOAA was determined 6 hr after administration in two tests: the maximal electroshock seizure test and the pentetrazole seizure threshold test. AOAA had a definite and dose-dependent anticonvulsant effect in both tests (ed₅₀ 28 and 27 mg/kg, respectively), but in a range being potentially lethal (ld₅₀ 40 mg/kg). Supplementation with pyridoxine via the drinking water for 3 days (daily intake 29 mg/kg) elevated the ld₅₀ significantly to 70 mg/kg and increased the anticonvulsant effect, but was without influence on the inhibition of GABA-T or the levels of GABA in brain.     

Genotype-dependent effects of GABAergic agents on sedative properties of ethanol

Two lines of mice, selectively bred for differential sensitivity to the soporific effects of ethanol (ETOH), were administered GABAergic drugs in an effort to evaluate a role for GABA in ETOH sensitivity. ETOH sensitive Long-Sleep mice (LS) showed potentiated ETOH sedation when administered bicuculline, muscimol and aminooxyacetic acid (AOAA). ETOH-insensitive SS mice exhibited reduced ETOH sedation in the presence of the antagonists, bicuculline and picrotoxin, and potentiated sedation in the presence of muscimol and AOAA. These changes in narcosis duration were interpreted as central effects, since blood ethanol levels at waking from ETOH sedation varied with GABAergic drug treatment. Picrotoxin antagonized pentobarbital-induced nacrosis in both lines, but to a greater extent in SS mice. These and other experiments with a genetically heterogeneous stock suggest GABA involvement in genotype-dependent ETOH sensitivity, but do not support a simple role of GABA receptor involvement.     

Enhancement of pharmacologic responses of pentobarbital by dopram

The effect of Dopram (doxapram hydrochloride, A. H. Robins Co.) on the pharmacologic responses to pentobarbital was evaluated. In naive and pentobarbital-tolerant mice, Dopram was shown to enhance significantly sodium pentobarbital-induced narcosis in a dose-related manner. The effect of the duration of action of Dopram on pentobarbital narcosis also was assessed. It was observed that Dopram (40 mg/kg, i.p.) significantly increased pentobarbital-induced narcosis even when administered 2 hr prior to challenge with sodium pentobarbital (60 mg/kg, i.p.) A significantly increased hypothermic response to sodium pentobarbital was seen in Dopram-treated animals. The half-life of pentobarbital in brain and serum was shown to be increased significantly in animals receiving Dopram, 40 mg/kg, i.p. The waking brain and serum pentobarbital concentrations were not significantly different in either group. These studies show that Dopram potentiates pentobarbital's effects. Further study is necessary to determine the sites of operation and mechanism of this potentiation.     

Development of tolerance to the effects of vigabatrin (gamma-vinyl-GABA) on GABA release from rat cerebral cortex, spinal cord and retina.

1. The effects of acute and chronic vigabatrin (gamma-vinyl-GABA) (GVG) administration on gamma-aminobutyric acid (GABA) levels and release in rat cortical slices, spinal cord slices and retinas were studied. 2. GVG (250 mgkg-1 i.p.) administered to rats 18 h before death (acute administration) produced an almost 3 fold increase in GABA levels of the cortex and spinal cord and a 6 fold increase in retinal GABA. The levels of glutamate, aspartate, glycine and taurine were unaffected. 3. When GVG (250 mgkg-1 i.p.) was administered daily for 17 days (chronic administration) a similar (almost 3 fold) increase in cortical GABA occurred but the increases in spinal and retinal GABA were reduced by approximately 40%. 4. Acute administration of GVG strikingly increased the potassium-evoked release (KCl 50 mM) of GABA from all three tissues. This enhanced evoked release was reduced by about 50% in tissues taken from rats that had been chronically treated with GVG. 5. Acute administration of GVG reduced GABA-transaminase (GABA-T) activity by approximately 80% in cortex and cord and by 98% in the retina. Following the chronic administration of GVG, there was a trend for GABA-T activities to recover (significant only in cortex). Acute administration of GVG had no effect on glutamic acid decarboxylase (GAD) activity in cortex or spinal cord. However, chronic treatment resulted in significant decreases in GAD activity in both the cortex and cord (35% and 50% reduction respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

3-Mercaptopropionic acid: convulsant properties, effects on enzymes of the gamma-aminobutyrate system in mouse brain and antagonism by certain anticonvulsant drugs, aminooxyacetic acid and gabaculine.

Subcutaneous injection of 3-mercaptopropionic acid (MP) into mice caused severe convulsions which started after about 6 min and were paralleled by a large, reversible inhibition of glutamate decar?ylase (GAD) and activation of (GABA)-α-oxoglutarate aminotransferase (GABA-T) in the brain. The central (GABA) level, determined by a newly developed gas Chromatographic method, was not altered after administration of the CD 97 of MP (60 mg/kg) but decreased after doubling or tripling the dose. Protection against the convulsions elicited by MP could be effected by pretreatment with phenobarbital, phenytoin, diazepam, carbamazepine, sodium valproate and trimethadione but not by ethosuximide and dimethadione. The ED 50's of the respective anticonvulsants against MP were similar to those determined against picrotoxin but, except in the case of trimethadione clearly less than those against strychnine-induced convulsions. All anticonvulsants effective against the convulsions of MP reversed the activation of GABA-T and tended to antagonize the inhibition of GAD caused by MP whereas dimethadione and ethosuximide were devoid of such action. The dissociative anaesthetic ketamine, which suppressed the MP-induced convulsions only at doses approaching the anaesthetic level, also failed to antagonize the alterations in the enzyme activities. Aminooxyacetic acid (AOAA) and gabaculine ((?)-5-amino-1,3-cyclohexadiene car?yclic acid) had a dose-dependent anticonvulsant effect against MP (ED 50 27 mg/kg s. c. and 135 mg/kg i. p., respectively) but at doses which were potentially (AOAA) or absolutely (gabaculine) lethal (LD 50 40 mg/kg and 62 mg/kg, respectively). Both drugs antagonized the inhibition of GAD caused by MP, reduced the activity of GABA-T to zero and raised the central level of GABA by more than 500 per cent.The results suggest a role played by the GABA system in the convulsant action of M P and in the antiseizure activity of several clinically useful anticonvulsants as well as AOAA and gabaculine. With respect to the GABA system, MP seems to be a useful tool in studies of experimental epilepsy.     

Effects of acute and chronic pentobarbitone on the gamma-aminobutyric acid system in rat brain

The effects of an acute anaesthetic dose and of chronic administration of pentobarbitone have been investigated on the GABA system in rat brain. This was done by estimating the cerebral γ-aminobutyric acid (GABA) concentration, the activities of both l-glutamate 1-carboxylyase (GAD) and 4-aminobutyrate: 2-oxoglutarate aminotransferase (GABA-T), and also the rate of ³H-GABA disappearance following its intracisternal injection. Neither acute nor chronic barbiturate administration caused any marked changes in the GABA concentrations or the enzyme activities. The exponential disappearance curves observed after injection of a pulse label of ³H-GABA were resolved into “fast” and “slow” components. Acute pentobarbitone was found to significantly decrease the rate constant of the fast component, whilst chronic pentobarbitone significantly decreased the rate constant of the slow component. The possible morphological correlates of these components are discussed. It is concluded that pentobarbitone has distinct actions on the GABA system which are different from those of other central nervous system depressants.     

Anticonvulsant and biochemical effects of inhibitors of GABA aminotransferase and valproic acid during subchronic treatment in mice

Mice were treated with different doses of the GABA aminotransferase (GABA-T) inhibitors aminooxyacetic acid, gamma-acetylenic acid, gamma-vinyl GABA and ethanolamine-O-sulphate via the drinking water for periods of 1-12. All drugs caused marked elevations of whole brain GABA concentrations within 4 days of treatment which were associated with increases in the electroconvulsive threshold. However, the effect on seizure threshold could not be enhanced by an increase in the daily dosage of the GABA-T inhibitors and, especially with higher doses, tolerance to the anticonvulsant effect developed. At least in part, this finding may be attributed to a decrease in the activity of glutamic acid decarboxylase (GAD), the enzyme responsible for GABA synthesis. On the other hand, with valproic acid (VPA) no tendency towards a reduced anticonvulsant effectiveness during medication was observed. VPA caused only non-significant increases in cerebral GABA levels but elevated brain GAD activity significantly. No behavioral changes were seen following subchronic administration of GABA-T inhibitors and VPA except in cases where the daily fluid intake was markedly reduced. Our data suggest that the anticonvulsant efficacy of long term treatment with GABA-T inhibitors is limited by the development of compensatory mechanisms, such as reduction of GAD activity, which in turn reduce the amount of GABA available for synaptic transmission, though overall GABA concentrations in the brain are highly elevated. Drug such as VPA which cause only moderate effects on GABA metabolism seem superior in this respect.     

Changes in brain levels of cyclic nucleotides and gamma-aminobutyric acid in barbiturate dependence and withdrawal.

Rats exposed to chronic intake of sodium barbital maintained high circulating levels of barbital in blood and brain and exhibited increased sensitivity ot audiogenic convulsions during the withdrawal period. Levels of gamma-aminobutyric acid (GABA), glutamate, guanosine 3',5'-monophosphate (cyclic GMP) and adenosine 3',5'-monophosphate (cyclic AMP) were measured in selected brain regions after sacrifice with high power microwave inactivation. Cyclic GMP during chronic barbital administration was significantly lower than controls in most brain regions, especially the hindbrain. During the withdrawal period cyclic GMP in the cerebellum was significantly increased, while returning at least to control levels in all other regions. GABA throughout the brain tended to be reduced during barbital dependence, while cyclic AMP and glutamate levels remained unchanged in all groups. These results indicate a possible role for cyclic GMP in the mediation of the central nervous system response during barbiturate dependence and withdrawal.     

Gamma-aminobutyric acid controls the mouse hypothalamic-pituitary-testicular response to the presence of female.

The role of gamma-aminobutyric acid (GABA) in the control of plasma testosterone was studied on male mice of inbred strains (CBA/Lac, A/He and BALB/c) exposed to a sexually receptive female in the same cage but separated by a partition. Within 40 minutes, testosterone levels in plasma increased 1.5-3.5 times depending upon the mouse genotype. This process could be completely blocked if GABA accumulation was induced by pretreatment with the GABA transaminase inhibitor, aminooxyacetic acid (AOAA), or by emotional stress induced by 40 min of restraint. Neither bicuculline-induced blockade of GABA receptors nor a decrease of GABA concentration induced by prior administration of thiosemicarbazide (an inhibitor of glutamate decarboxylase), affected the increase of plasma testosterone that occurred in response to presentation of a receptive female. However, at sexual arousal, the bicuculline blockade of GABA receptors significantly reduced the inhibitory effects of both AOAA administration and emotional stress on plasma testosterone levels. We conclude that the inhibitory effect of emotional stress on female-induced activation of testicular endocrine function is mediated, at least in part, via activation of bicuculline-sensitive receptors.     

Effect of 2-pyrrolidone on the concentration of GABA in rat tissues

The effects of 2-pyrrolidone, a cyclic lactam of GABA, were studied on blood and organ levels of 2-pyrrolidone, GABA, glutamic acid, glutamate decarboxylase (GAD) and GABA-transaminase (GABA-T). When administered i.p., the only significant effects observed were increases of brain and liver 2-pyrrolidone. In contrast, regular oral administration for 7 months produced significant increases of GABA and glutamic acid in brain and of glutamic acid alone in liver while GAD decreased in brain and increased in liver; GABA-T was unchanged. A new method for the synthesis of radioactive 2-pyrrolidone was set up and the enzymatic conversion of 2-pyrrolidone to GABA was measured by an original procedure. The results obtained in vitro by this method on the conversion of 2-pyrrolidone to GABA catalyzed by tissue slices, together with the observed inhibition of the GABA-dependent oxygen consumption by 2-pyrrolidone, partially explain the effects of the oral administration.     

Changes of taurine content in the brain tissue of barbiturate-dependent rats

The concentrations of taurine, γ-aminobutyric acid (GABA), glutamic acid and aspartic acid in the brain of barbiturate-dependent rats were determined. Barbiturate-dependent rats, engendered by long-term administration of feed containing barbital sodium, showed signs of withdrawal, such as spontaneous convulsions and marked loss of body weight. Prolonged administration of barbital sodium caused a significant increase in cerebellar taurine content; soon after withdrawal of the drug the content returned to normal. The taurine content in the cerebral cortex increased 48 hr after the withdrawal. These changes of taurine content occurred in the brain but not in other organs. The GABA content of the cerebral cortex and brain stem decreased significantly during barbiturate administration and returned to normal within 48 hr after withdrawal of barbiturate. A significant decrease of aspartate content in the cerebral cortex was also observed at 48 hr after barbiturate withdrawal, but the glutamate content did not change during or after drug administration.     

Effects of inhibitors of GABA-transaminase on hole-board exploration and on temperature. Relation with effects on quasi-morphine abstinence behaviour induced by sodium dipropylacetate

Four inhibitors of gamma-aminobutyric acid transaminase (GABA-T) were investigated together with respect to their effects on hole-board exploration and temperature and the relation with effects on quasi-morphine-abstinence behaviour induced by dipropylacetate (DPA) in rats. Amino-oxyacetic acid (AOAA), gamma-acetylenic-GABA (GAG), gamma-vinyl-GABA (GVC) and ethanolamine-O-sulfate (EOS) were found to reduce hole-board exploration especially in the higher doses used, although the time-course of the effect was different for the compounds. For EOS and GVG the decrease in hole-board exploration paralleled a strong hypothermic effect. The compounds AOAA and GAG exerted a less and more transient hypothermic effect. However, the decrease in hole-board exploration did not fall in with this decrease in temperature. AOAA and GAG were found to decrease DPA-induced body shakes and locomotor activity, while GVG and EOS had no effect on body shakes and transient effects but opposite to each other, on locomotor activity. The efficacy of the GABA-T-inhibitors was measured biochemically, and the influence on the activity of glutamate decarboxylase (GAD) was also determined. AOAA and GAG were found to be strong inhibitors of GABA-T whereas the other two compounds were less efficient in the used doses. In addition AOAA and GAG influenced the activity of GAD strongly, while using GVG only a small decrease was found. The results suggest that the anti-quasi-withdrawal, the sedative and the hypothermic effects are not related to each other nor related to an effect on GABA-T. The suppressive effects on quasi-withdrawal body shakes, however, could be related to the inhibition of GAD and a hypothesis involving a compartmentalized action of DPA on GABA-metabolism has been proposed.     

Comparison of the effects of acute and subchronic administration of Aroclor 1254, a commercial mixture of polychlorinated biphenyls, on pentobarbital-induced sleep time and [14C]pentobarbital disposition in mice

We have reported previously that polychlorinated biphenyls (PCBs) alter neurochemistry and suppress spontaneous locomotor activity in mice. The present study was initiated to determine whether orally administered (Aroclor 1254) would potentiate pentobarbital-induced sleep time. Sleep time was enhanced significantly by Aroclor 1254 (500 mg/kg) given 0 to 8 h prior to pentobarbital, with the peak effect occurring at 2 h. This effect was demonstrated to be dose-responsive in the range of 5 to 25 mg/kg given 2 h prior to pentobarbital, but only slightly larger increments in sleep time were observed with higher doses of PCBs (50, 100, 250, and 500 mg/kg). Administration of vehicle or Aroclor 1254 (30 or 100 mg/kg) for 14 successive days reduced sleep time when pentobarbital was given 45 min after the last dose of vehicle or Aroclor 1254, with a further reduction when pentobarbital was given 24 h after the last dose. As a correlate to the sleep-time studies, levels of pentobarbital and metabolites were measured in brain, liver, and plasma of mice that had received varying doses of Aroclor 1254 2 h prior to [14C]pentobarbital. Elevated levels of pentobarbital and decreased levels of metabolites were found after acute administration of Aroclor 1254 during a period of time when Aroclor 1254-treated mice were still asleep. These effects of Aroclor 1254 on pentobarbital disposition were found to be dose-dependent. Brain levels of pentobarbital in mice after 14 d of Aroclor 1254 treatment (30 mg/kg) were less than those in vehicle-treated animals, and these levels were consistent with the reduced sleep times. Thus, a correlation between pentobarbital brain levels and sleep time in both Aroclor 1254-treated and nontreated animals suggests that Aroclor 1254 does not alter pentobarbital narcosis by a direct action on the brain. Rather, acutely administered Aroclor 1254 may be augmenting sleep time by competing with pentobarbital for metabolic sites in the liver, while chronically administered Aroclor 1254 induces pentobarbital metabolism.     

Exposure to polychlorinated naphthalenes affects GABA-metabolizing enzymes in rat brain

There is substantial evidence that polychlorinated naphthalenes (PCNs) are widespread global environmental pollutants, which accumulate in biota. The aim of our study was to characterize the effect of prolonged PCNs exposure on γ-aminobutyric acid (GABA) metabolism in rat brain regions with a high amount of GABAergic neurons (cerebellum, brain stem and basal ganglia). PCNs mixture was administered intragastrically for 7, 14 and 21 days in a dose 10 mg/kg of body weight daily, and next the activity of glutamate decarboxylase (GAD), GABA-aminotransferase (GABA-T), succinic semialdehyde dehydrogenase (SDH) and succinate dehydrogenase (SSA-DH) was assayed. PCNs administration altered all examined activities in the selected brain areas, except GAD in basal ganglia. The results suggest the correlation between PCNs action and disturbance in GABA metabolism in rat brain. Moreover, the chronic PCNs intoxication increased SDH-mediated activation of TCA cycle, and it may be a kind of protective mechanism developed in nervous tissue in response to administration of toxic compounds.     

β-细辛醚对癫痫大鼠脑皮质Glu、GABA、GAD的影响

目的:研究β-细辛醚对慢性点燃癫痫大鼠脑皮质谷氨酸(Glu)、γ-氨基丁酸(GABA)及谷氨酸脱羧酶(GAD)的影响。方法:将大鼠随机分为5组,即β-细辛醚高、中、低(100、50、25mg.kg-1)剂量组,阳性药(苯妥英钠)对照组,阴性(基质)对照组,灌胃给药。以青霉素点燃大鼠慢性癫痫,采用高效液相色谱-荧光法测定脑皮质Glu、GABA的含量,以免疫组化法检测GAD65活性。结果:β-细辛醚能显著降低癫痫大鼠脑皮质Glu、GABA的含量,降低GAD65表达,并呈明显的量效关系。结论:β-细辛醚能减少癫痫大鼠脑内兴奋性氨基酸毒性作用,减轻GABA参与的迟发性神经元损害。