Interaction of the β-carboline harmaline with a GABA-benzodiazepine mechanism: an electrophysiological investigation on rat hippocampal slices

An interaction of harmaline (HA), a β-carboline, with benzodiazepine (Bzd) receptors, has been reported. HA perfusion induced a similar, although less potent, depressing effect as clonazepam (CLO) on the amplitude of the population spikes (PS) evoked by Schaffer collateral stimulation in the CA1 area of rat hippocampal slices. The suppressant effect of both CLO and HA on PS amplitude was reversed by simultaneous perfusion of the GABA antagonist picrotoxin. These results suggest that HA acts as a weak or partial agonist at Bzd receptors.     

Tonic and phasic differential GABAergic inhibition of synaptic actions of joint afferents in the cat

The aim of this study was to examine the functional organization of the spinal neuronal networks activated by myelinated afferent fibers in the posterior articular nerve (PAN) of the anesthetized cat. Particular attention was given to the tonic and phasic GABAa inhibitory modulation of these networks. Changes in the synaptic effectiveness of the joint afferents were inferred from changes in the intraspinal focal potentials produced by electrical stimulation of the PAN. We found that conditioning stimulation of cutaneous nerves (sural, superficial peroneus and saphenous) and of the nucleus raphe magnus often inhibited, in a differential manner, the early and late components of the intraspinal focal potentials produced by stimulation of low and high threshold myelinated PAN afferents, respectively. The degree of the inhibition depended on the strength of both the conditioning and test stimuli and on the segmental level of recording. Conditioning stimulation of group I muscle afferents was less effective, but marked depression of the early and late focal potentials was produced by stimuli exceeding 5 xT. The i.v. injection of 1–2.5 mg/kg of picrotoxin, a GABAa blocker, had relatively minor effects on the early components of the PAN focal potentials, but was able to induce a significant increase of the late components. It also reduced the inhibitory effects of cutaneous and joint nerve conditioning on PAN focal responses. Conditioning autogenetic stimulation with high-frequency trains depressed the PAN focal potentials. The late components of the PAN responses remained depressed several minutes after discontinuing the conditioning train, even after picrotoxin administration. The present observations indicate that the neuronal networks activated by the low threshold PAN afferents show a relatively small post-activation depression and appear to be subjected to a minor tonic inhibitory GABAa control. In contrast, the pathways activated by stimulation of high threshold myelinated afferents have a strong post-activation depression and are subjected to a significant tonic GABAergic modulation. These contrasting features, together with the phasic differential GABAergic inhibition of the responses produced by stimulation of the different populations of joint afferents, may contribute to the preservation of the original information on joint position transmitted by large diameter joint afferents, in contrast with the tonic presynaptic inhibition exerted on the fine myelinated joint afferents, which may be involved in the adjustment of compensatory reactions to inflammation.     

SEASONAL AND ENVIRONMENTAL TEMPERATURE VARIATION IN THE OCCURRENCE OF ISCHEMIC STROKES AND INTRACEREBRAL HEMORRHAGES IN A TURKISH ADULT POPULATION

Seasonal and weather influence on the incidence of cerebrovascular disease has been reported previously. The aim of this retrospective study was to determine whether the time of onset of ischemic strokes (IS) and intracerebral hemorrhages (ICH) were associated with the environmental temperature or the time, as a month or season, in our region. We analyzed the monthly and seasonal incidence of stroke between 1997 and 2001. Four hundred and fifty-one cases were admitted to our clinic (IS; n = 288 and ICH; n = 163), and aged from 16 to 94 years. The study was carried out in province of Van in eastern Turkey. The present study demonstrated a peak occurrence of IS in August (n = 41). For ICH, we observed a peak occurrence in July (n = 23). The highest number of IS occurred in summer (n = 108), the most moderate amount in autumn (n = 81), and the least in spring (n = 38). The hemorrhagic events were highest in summer (n = 58), most moderate in winter (n = 61), and lowest in spring (n = 31) and autumn (n = 32). There was a significantly greater incidence of IS and ICH during the summer than any other season in the province of Van, Turkey. This may reflect the role of weather temperature in the development of stroke and allow us to take preventive measures.     

针刺抗脑缺血损伤时脑内γ-氨基丁酸的作用

目的观察γ-氨基丁酸在针刺抗脑缺血中的作用,探讨电针治疗脑缺血的中枢机制.方法采用大脑中动脉阻塞(MCAO)大鼠为动物模型,并应用H&E染色和免疫组化的方法,观察缺血再灌及电针治疗后不同时间,不同脑区细胞内γ-氨基丁酸(GABA)的含量,及GABA受体阻断剂-Picrotoxin对缺血损伤和针刺效应的影响.结果电针能明显上调缺血2 h,再灌30 min时皮质、海马和丘脑的胞内GABA的含量,并缩小缺血损伤区;与单纯缺血组相比有显著差异(P＜0.05).还观察到给予Picrotoxin,以及同时给予Picrotoxin和电针时,大鼠脑缺血侧的梗死面积增大,细胞残存率减小,与单纯电针组亦有显著差异(P＜0.01).结论电针抗脑缺血的神经保护作用可能部分与上调GABA有关.     

脑内GABA能神经元对红藻氨酸中枢性心血管效应的影响

采用侧脑室微最注射法证明,谷氯酸受体哑型激动剂红藻氨酸(KA)可依剂量性地升高大鼠血压和加快心率。预先给予GABA合成抑制剂氮基脲140 mg/kg ip或GABA拮抗剂印防己毒1 mg/kg iv均可明显增强KA的作用;而GABA转氨酶抑制剂氨氧乙酸25μg/rat icv明显减弱KA的作用。结果表明,脑内GABA能神经元功能受抑,KA的中枢性心血管效应增强。从而推测,脑内GABA能神经元与谷氯酸能神经元之间相互制约,共同参与中枢性调节心血管的活动。     

Inhibitory action of CGS 21680 on cerebral cortical neurons is antagonized by bicuculline and picrotoxin—is GABA involved?

The possibility of an involvement of endogenously released GABA in the inhibitory actions of A₁ and A_2a adenosine receptor agonists on rat cerebral cortical neurons discharges was examined using the GABA_A antagonists bicuculline and picrotoxin. The A₁ agonist N⁶-cyclopentyladenosine (CPA), the A_2a agonist CGS 21680 and the non-selective receptor agonist, adenosine, depressed neuronal firing. Applications of bicuculline or picrotoxin enhanced the spontaneous firing rate of cortical neurons, indicating the presence of ongoing GABA-ergic inhibition. Antagonism of GABA_A receptors blocked the depressant effects of CGS 21680 on neuronal firing; was without effect on CPA-evoked inhibitions and tended to reduce the duration of adenosine-evoked inhibitions. These results suggest that the depressant effects of A_2a receptor activation are due to an increase in GABA-ergic inhibition, likely as a consequence of increased GABA release. GABA does not appear to be involved in adenosine A₁ receptor-mediated inhibition of neuronal firing.     

Gnawing and changes in reactivity produced by microinjections of picrotoxin into the superior colliculus of rats

Lesions of the superior colliculus in rats attenuate the oral stereotypy produced by systemic administration of dopamine agonists. Current evidence suggests that such drugs affect the superior colliculus by reducing transmission in the inhibitory GABAergic nigrotectal pathway. To investigate whether the superior colliculus plays a direct role in producing stereotyped oral movements, the present experiment therefore examined the effects of collicular microinjections of the GABA antagonist picrotoxin on the behaviour of rats observed in an open-field.Gnawing was observed after injections of picrotoxin (25 ng) into sites in the intermediate and deep layers of the superior colliculus, consistent with the superior colliculus playing a direct part in producing the stereotyped gnawing seen after systemic administration of dopamine agonists. However, gnawing was only observed after a period in which the animal showed strong avoidance reactions, to stimuli that normally evoked orienting or little reaction. This change in reactivity was observed after injections of picrotoxin into all parts of the colliculus, but the most sensitive (responding to doses as low as 12.5 ng) were mainly in the superficial and intermediate layers. It appears that there may be more than one GABAergic system within the superior colliculus.     

Effects of glycine on neurons in the rat substantia nigra zona compacta: in vitro electrophysiological study

The effects of bath-applied glycine to substantia nigra zona compacta neurons of rat were investigated by intracellular recording techniques in vitro. Superfusion of glycine (1 mM) in the medium hyperpolarized 53% of the neurons recorded with KCl electrodes, whereas 32% of the cells were depolarized. The remaining 15% of neurons was hyperpolarized and then depolarized by the amino acid. In spite of these membrane changes, the action potential firing was depressed. Both hyperpolarization and depolarization were correlated to an outward and an inward current, respectively, when recording in single-electrode voltage-clamp mode. In response to bath application of glycine, the neurons showed a concentration-dependent conductance increase. Micromolar concentrations of glycine (100-300 microM) in the superfusion medium produced a membrane hyperpolarization (outward current) in most of the tested cells, whereas millimolar concentration of amino acid could cause depolarization (inward current) in the same neurons. When the recording electrodes contained K acetate, only hyperpolarizations (outward current) were produced. The potential and current changes and the increase in membrane conductance produced by glycine showed little desensitization when neurons were recorded with K acetate electrodes. The mean reversal potential for the membrane hyperpolarization was -80 mV with intracellular electrodes containing KCl and -84 mV with electrodes containing K acetate. The mean null potential for the depolarizing effect was -46 mV. The reversal potential for the glycinergic responses was shifted to less negative values upon lowering the extracellular concentration of chloride or increasing the extracellular concentration of potassium. Strychnine (1-10 microM) reversibly antagonized both the conductance increase and the membrane changes produced by glycine. Bath application of bicuculline (100 microM) and picrotoxin (200 microM) did not affect glycine responses, while depressing the actions of GABA and muscimol. It is concluded the glycine exerts an inhibition on substantia nigra zona compacta neurons by acting on strychnine-sensitive receptors. The membrane effects produced by glycine result from the activation of a chloride current. In addition, the simultaneous involvement of potassium ions may contribute to the overall effects of glycine.     

第四脑室周围组织的GABA在家兔低氧循环反应中的作用

本工作探讨第了室周围区域的ＧＡＢＡ系统在家兔低氧循环反应中的作用。护林 ，以经人工呼吸机吸入含氧量为１１％的低氧混合气（模拟海拔高度６５００ｍ），对照组（ｎ＝１１）第四脑室注射生理盐水１００μｌ；实验组第四脑室注射Ｐｉｃｒｏｔｏｘｉｎ１０μｇ／１００μｌ。结果显示：对照组的经四脑室注射后对ＭＡＰ和ＨＲ均无明显影响；且的经四脑一ＭＡＰ明显升高，ＨＲ无显著变化。两组运行均地第四室注射１０分钟时进行低氧     

Effects of GABAergic drugs on physostigmine-induced yawning in rats

In the present work the effects of GABA agonists and antagonists on yawning induced by physostigmine have been studied. Intraperitoneally (IP) injection of physostigmine (0.05–0.3 mg/kg) induced dose-related yawning in rats. The maximum yawning response was observed with 0.2 mg/kg of the drug. The GABA agonists muscimol (1–4 mg/kg) and baclofen (0.125–1 mg/kg) decreased yawning induced by physostigmine (0.2 mg/kg) dose dependently. Combination of both GABA agonists elicited greater inhibition of yawning. The GABA-A antagonists bicuculline or picrotoxin but not the GABA-B antagonist phaclofen reduced the inhibitory response induced by muscimol, whereas phaclofen but not bicuculline or picrotoxin reduced baclofen's inhibitory effect. Administration of bicuculline, picrotoxin or phaclofen also decreased the yawning induced by physostigmine. However, when the GABA-A and GABA-B antagonists were employed in combination, the inhibitory responses of both drugs were lost. It is concluded that GABA-A and/or GABA-B receptor stimulation may inhibit physostigmine-induced yawning.