EFFECTS OF SYSTEMIC AND LOCAL ETHANOL ON RESPONSES OF RAT CEREBELLAR PURKINJE NEURONS TO IONTOPHORETICALLY APPLIED GAMMA-AMINOBUTYRIC-ACID
EFFECTS OF SYSTEMIC AND LOCAL ETHANOL ON RESPONSES OF RAT CEREBELLAR PURKINJE NEURONS TO IONTOPHORETICALLY APPLIED GAMMA-AMINOBUTYRIC-ACID
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DOI：
10.1016/0006-8993(95)00285-x
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发表时间：
1995-07-31
期刊：
影响因子：
2.9
通讯作者：
WOODWARD, DJ
中科院分区：
文献类型：
--
作者：
LEE, RS;SMITH, SS;WOODWARD, DJ
本研究的目的是：（1）确定急性全身或局部应用乙醇（ETOH）对小脑浦肯野细胞（P-细胞）对离子电渗应用γ-氨基丁酸（GABA）的反应的影响;（2）表征Ro 15 -4513（一种推定的ETOH-GABA相互作用拮抗剂）对ETOH诱导的GABA反应性变化的影响。在记录阶段之前，用氟烷麻醉雄性Sprague-Dawley大鼠（230-370 g），并植入腹膜内导管以给予ETOH（1.0-2.0 g/kg）。单个P细胞的细胞外活性用五筒微量移液器的中心筒记录，其他筒用于记录部位的GABA的微离子电渗和ETOH的电渗。自发放电和响应的P-细胞的GABA进行了监测，在前ETOH控制和1-1.5小时后，全身或电渗给药ETOH。自发性P细胞放电的短暂抑制通常在全身ETOH注射后4-8分钟内观察到。这种作用在19只受试大鼠中的10只中持续2-4分钟。在ETOH注射后10和90分钟，小脑P细胞的GABA介导的抑制反应相对于ETOH前值增加了45-50%。预先给予咪唑苯并二氮卓Ro 15 -4513（4-6 mg/kg）未能拮抗ETOH诱导的GABA介导的抑制增强或ETOH产生的大鼠小脑P细胞自发性P细胞活性的短暂抑制。在这些研究中，电刺激应用的ETOH对自发性P细胞活动产生了有效的抑制，从而阻止了对GABA的单位反应的进一步增强。这些结果表明，在清醒、行为正常的动物中，全身给予轻度中毒的ETOH剂量可增强GABA对小脑P细胞放电的抑制作用。
The goals of this study were: (1) to determine the effects of acute systemic or local application of ethanol (ETOH) on the response of cerebellar Purkinje cells (P-cells) to iontophoretically applied gamma-aminobutyric acid (GABA) and (2) to characterize the effects of Ro15-4513, a putative antagonist of ETOH-GABA interactions, on ETOH-induced changes in GABA responsiveness. Male Sprague-Dawley rats (230-370 g) were anesthetized with halothane and implanted with intraperitoneal catheters for administration of ETOH (1.0-2.0 g/kg), before the recording session. Extracellular activity of single P-cells was recorded with the central barrel of a five-barrel micropipette, the other barrels of which were used for microiontophoresis of GABA and electro-osmosis of ETOH at the recording site. Spontaneous discharge and response of P-cells to GABA were monitored during a pre-ETOH control and for 1-1.5 h after systemic or electro-osmotic administration of ETOH. Transient suppression of spontaneous P-cell discharge was usually observed within 4-8 min of systemic ETOH injection. This effect lasted 2-4 min in 10 out of 19 rats tested. GABA-mediated inhibitory responses of cerebellar P-cells were increased by 45-50% relative to pre-ETOH values at 10 and 90 min post-ETOH injection. Prior administration of the imidazobenzodiazepine Ro15-4513 (4-6 mg/kg) failed to antagonize either the ETOH-induced enhancement of GABA-mediated inhibition or the transient inhibition of spontaneous P-cell activity rat cerebellar P-cell produced by ETOH. In these studies, electro-osmotically applied ETOH produced a potent suppression of spontaneous P-cell activity which precluded further augmentation of unit responses to GABA. These results show that doses of systemically administered ETOH which are mildly intoxicating in the awake, behaving animal, enhance the inhibitory action of GABA on cerebellar P-cell discharge.