Effect of diazepam on reactivity of hippocampal neurons during blockade of the GABA-ergic system

Bulletin of Experimental Biology and Medicine -     

隔区通过GABA_A抑制缰核活动产生电针镇痛作用

通过多管微电泳记录大鼠缰核单位放电和测定痛阐的方法观察到：ＧＡＢＡＡ可完全抑制缰植的自发放电；电刺激隔区强力抑制缰核的自发放电，Ｂｉｏｕｏｕｌｌｉｎｅ则使该作用减弱；双侧缰核内微量注射ＧＡＢＡ使痛阐明显升高，Ｂｉｃｕｃｕｌｌｉｎｅ则相反并拮抗电针镇痛效应。提示隔区通过ＧＡＢＡ抑制缰核活动产生电针镇痛作用     

Bicuculline-induced brain activation in mice detected by functional magnetic resonance imaging.

Dynamic measurements of local changes in relative cerebral blood volume (CBV(rel)) during a pharmacological stimulation paradigm were performed in mice. Using magnetite nanoparticles as an intravascular contrast agent, high-resolution CBV(rel) maps were obtained. Intravenous administration of the GABA(A) antagonist bicuculline prompted increases in local CBV(rel) as assessed by MRI with a high spatial resolution of 0.2 x 0.2 mm(2) and a temporal resolution of 21 s. Signal changes occurred 20-30 s after the onset of drug infusion in the somatosensory and motor cortex, followed by other cortical and subcortical structures. The magnitudes of the CBV(rel) increases were 18% +/- 4%, 46% +/- 14%, and 67% +/- 7%, as compared to prestimulation values for the cortex, and 9% +/- 3%, 25% +/- 4%, and 36% +/- 7% for the caudate putamen for bicuculline doses of 0.6, 1.25, and 1.5 mg/kg, respectively. On-line monitoring of transcutaneous carbon dioxide tension PtcCO(2) reflecting arterial PaCO(2) did not show any alteration during the stimulation paradigm. One of five of the mice receiving the highest bicuculline dose, and three of seven receiving the intermediate dose displayed a different cortical response pattern. After a CBV(rel) increase of 40% lasting for approximately 1 min, significant CBV(rel)reductions by 80% have been observed. Subcortical structures did not display this behavior. The present study suggests that this noninvasive approach of functional MRI (fMRI) can be applied to study drug-induced brain activation by central nervous system (CNS) drugs in mice under normal and pathological situations.     

Anticonvulsant effects of neurotropin

Department of Normal Physiology, N. I. Pirogov Odessa Medical Institute. Department of Normal Physiology, I. M. Sechenov First Moscow Medical Institute. Laboratory of General Pathology of the Nervous System, Research Institute of General Pathology and Pathophysiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 111, No. 1, pp. 49–52, January, 1991.     

Injections of picrotoxin and bicuculline into the amygdaloid complex of the rat: an electroencephalographic, behavioural and morphological analysis

Bicuculline methiodide (0.5-3 nmol) and picrotoxin (0.5-4 nmol) were injected uni- or bilaterally into the rat amygdala and the resulting behavioural, electroencephalographic and morphological alterations were studied. In rats treated unilaterally with lowest doses of either bicuculline or picrotoxin (0.5 and 1 nmol) increase in the locomotor activity, occasional myoclonus of the hindlimbs and wet dog shakes were observed. At doses of 2-3 nmol, both gamma-aminobutyrate antagonists produced a sequence of repetitively occurring behavioural alterations including limbic gustatory automatisms, tremor and myoclonus of the forelimbs, head nodding and rearing, that developed over 15-30 min and built up progressively into the recurrent motor limbic seizures lasting for 1-6 h. In animals injected bilaterally with either bicuculline (0.5-3 nmol) or picrotoxin (0.5-3 nmol) motor limbic seizures rapidly developed into the status epilepticus lasting for several hours. Bicuculline and picrotoxin produced both ictal and interictal epileptiform activity in the electroencephalogram. A spectrum of electroencephalographic changes consisted of high voltage fast activity, slow and fast voltage spiking, paraoxysmal bursts and periods of postictal depression. The earliest electrographic alterations appeared in the amygdala and then rapidly spread to cortical areas. Electrographic seizures started 1-10 min after unilateral injections of large doses of bicuculline and pictrotoxin (2-4 nmol). Ictal periods lasted for 1-2 min, recurred every 5-10 min and were followed by periods of depression of the electrographic activity. Bilateral injections of large doses of both gamma-aminobutyrate antagonists (2-3 nmol) resulted in the status epilepticus. Morphological examination of frontal forebrain sections with light microscopy revealed a widespread damage to the amygdala, olfactory cortex, substantia nigra, thalamus, hippocampus and neocortex. Pretreatment of animals with diazepam prevented the build-up of convulsive activity and brain damage produced by bicuculline or picrotoxin. Muscimol retarded the appearance and shortened the duration of convulsive activity, but did not alter the sequence and intensity of seizures. The results indicate that gamma-aminobutyrate antagonists, bicuculline and picrotoxin when directly applied to the amygdala can elicit in rats motor limbic seizures, epileptic changes in the electroencephalogram indicative of repetitive limbic seizures, and status epilepticus accompanied by seizure-related brain damage.(ABSTRACT TRUNCATED AT 400 WORDS)     

Anticonvulsant phosphorus analogs of GABA

The dimethyl (I), diethyl (II), and di-isopropyl (III) esters of 3-amino-phenylphosphonic acid and diethyl 2-acetamidophenylphosphate (IV) were tested for inhibition of seizures induced by maximal electroshock (MES) and subcutaneous pentylenetetrazol (Metrazol) (scMet) and for neurotoxicity. Compound I was further tested for inhibition of seizures induced by subcutaneous bicuculline (scBic) and picrotoxin (scPic). Protective indices (P.I.) were compared with those reported for valproic acid (VPA) against MES and scMet and, in the case of I, with VPA, ethosuximide, trimethadione, and phenobarbital (scBic and scPic). The P.I. values of I are comparable to those of trimethadione, equal to VPA against scMet, but higher by factors of 2.6, 1.8, and 1.3 against MES, scPic and scBic, respectively.     

安定对大鼠脊髓损伤的保护作用及GABAA受体拮抗剂对此作用的影响

应用大鼠脊髓挤压伤模型来研究安定对大鼠挤压伤模型脊髓损伤后的保护作用,及GABAA受体拮抗剂bicuculline对此作用的影响。实验大鼠分为对照组、安定组、安定联合bicuculline组及bicuculline组,应用大鼠脊髓挤压伤模型观察药物作用72h后各组大鼠脊髓损伤体积变化。结果显示对照组大鼠脊髓损伤体积为(18.21±1.14)mm3;安定组大鼠脊髓损伤体积为(12.11±1.61)mm3,明显小于对照组(P<0.01);安定联合bicuculline组大鼠脊髓损伤体积为(16.34±1.59)mm3,大于安定组(P<0.01),但仍小于对照组(P<0.01);bicuculline组大鼠脊髓损伤体积为(18.45±1.98)mm3;与对照组相比无明显差异(P>0.05)。结论安定可明显减轻大鼠脊髓挤压损伤后的脊髓损伤程度,而GABAA受体拮抗剂bicuculline可拮抗此作用,说明安定通过与GABAA受体结合,可提高GABA与GABAA受体的结合力,从而上调GABA的抑制作用,减少谷氨酸的兴奋性毒性作用以达到保护脊髓的作用。     

γ-氨基丁酸A型受体调节哮喘动物模型气道重构的实验研究

目的 探讨γ-氨基丁酸A受体(GABAAR)拮抗剂荷包牡丹碱对于小鼠哮喘气道重构模型的干预作用.方法 BALB/C小鼠被随机分为4组:空白对照组、哮喘模型组、激素治疗组和荷包牡丹碱干预组.除空白对照组外其他各组小鼠在第1、7、14天通过腹腔注射10μg卵清蛋白(OVA)和100 μg Al(OH)3的PBS液致敏,从实验的第15～81天小鼠每天雾化吸人5%OVA溶液1h.从第15天开始,激素治疗组每天雾化吸入0.02%布地奈德溶液0.5h,荷包牡丹碱组每天鼻腔滴入20%荷包牡丹碱悬浊液50μl.于最后一次激发后24h放血处死小鼠,检测BALF中细胞总数、嗜酸性粒细胞和淋巴细胞,肺组织标本切片PAS染色检测粘蛋白糖原,Masson染色检测上皮下胶原沉积面积,免疫组织化学方法检测GABAARβ2和血管内皮生长因子(VEGF)的表达水平.结果 (1)荷包牡丹碱干预组BALF中细胞总数、嗜酸性粒细胞和淋巴细胞数分别为(20.50±2.40)×10 4、(8.30±0.23)×10 4和(4.20±0.05)×10 4,与对照组[(2.43±2.10)×10 4、(0.00±0.00)×10 4和(0.90±0.05)×10 4]和激素干预组[(5.50±1.90)×10 4、(3.60±0.25)×10 4和(1.90±0.03)×10 4]比较差异有统计学意义(均为P<0.01),与哮喘模型组[(20.40±1.80)×10 4、(8.80±0.14)×10 4和(4.20±0.10)×10 4]比较差异无统计学意义(P>0.05).(2)荷包牡丹碱干预组气道基底膜胶原沉积面积为(0.34±0.17)μm2/μm,与对照组[(0.27±0.02)μm2/μm]和激素干预组[(0.30±0.06)μm2/μm]比较差异无统计学意义(均为P>0.05),与哮喘模型组[(0.72±0.08)μm2/μm]比较差异有统计学意义(P<0.05).(3)荷包牡丹碱干预组PAS阳性细胞百分数为(19.00±2.08)%,与对照组[(0.00±0.0)%]、激素干预组[(30.00±1.66)%]和哮喘模型组[(58.00±1.57)%]比较差异有统计学意义(均为P<0.05).(4)荷包牡丹碱干预组GABAA受体β2-亚基表达阳性率为(11.30±2.7)%,与对照组[(2.00±0.7)%]和激素干预组[(7.3±1.58)%]比较差异有统计学意义(P<0.01和P<0.05),与哮喘模型组[(12.50±0.31)%]比较差异无统计学意义(P>0.05).(5)荷包牡丹碱干预组肺血管周围细胞VEGF表达阳性率为(10.60±1.20)%,与对照组[(1.70±0.34)%]和激素干预组[(8.30±0.78)%]比较差异有统计学意义(P<0.01和P<0.05),与哮喘模型组[(18.30±0.80)%]比较差异无统计学意义(P>0.05).结论 气道上皮细胞和气道平滑肌细胞广泛表达GABAARβ2,荷包牡丹碱吸入可以有效抑制粘液分泌和上皮下胶原沉积,其抑制粘液分泌的作用强于吸入激素,但不能减轻气道炎症水平,也不能抑制GABAARβ2和VEGF的表达.     

Neuropeptide Y,GABA and circadian phase shifts to photic stimuli

Circadian rhythms can be phase shifted by photic and non-photic stimuli. The circadian clock, anatomically defined as the suprachiasmatic nucleus (SCN), can be phase delayed by light during the early subjective night and phase advanced during the late subjective night. Non-photic stimuli reset the clock when presented during the subjective day. A possible pathway for the non-photic resetting of the clock is thought to originate from the intergeniculate leaflet, which conveys information to the SCN through the geniculohypothalamic tract and utilizes among others neuropeptide Y (NPY) and GABA as neurotransmitters. Photic and non-photic stimuli have been shown to interact during the early and late subjective night. Microinjections of NPY or muscimol, a GABA_A receptor agonist, into the region of the SCN can attenuate light-induced phase shifts during the early and late subjective night. The precise mechanism for these interactions is unknown.

In the current study we investigate the involvement of a GABAergic mechanism in the interaction between NPY and light during the early and late subjective night. Microinjections of NPY significantly attenuated light-induced phase delays and inhibited phase advances (P<0.05). The administration of bicuculline during light exposure, before NPY microinjection did not alter the ability of NPY to attenuate light-induced phase delays and block photic phase advances.

These results indicate that NPY attenuates photic phase shifts via a mechanism independent of GABA_A receptor activation. Furthermore it is evident that NPY influences circadian clock function via differing cellular pathways over the course of a circadian cycle.     

阿托品,荷包牡丹碱对家鸽（Columba livia）顶盖Ⅱa—f亚层与Ⅲ？…

目的：探讨阿托品（Ａｔｒｏｐｉｎｅ，ＡＴＲ）、荷 包牡丹碱（Ｂｉｃｕｃｕｌｌｉｎｅ，ＢＩＣ）对家鸽顶盖Ⅱａ－ｆ亚层与Ⅲ层神经元间突触传递的影响。方法：在孵育离体顶盖脑片标本上，采用脉冲方波民刺激Ⅱａ－ｆ亚层，利用玻璃微电极胞外记录技术记录Ⅲ层神经元放电频率。结果：Ⅲ层神经元对电刺激Ⅱａ－ｆ亚层有反应的２８个单位中，１３个单位（占４６．４％）表现为增频，１５个单位（占５３．６％）表现为减频。表现为增