氟桂利嗪对癫痫鼠痫性发作和脑电活动的影响

目的研究氟桂利嗪对青霉素致癎大鼠癎性发作和脑电活动的影响.方法用60只Wistar大鼠分4组,即对照组及氟桂利嗪10、20、40 mg·kg-1组,2 h后对照组和各实验组给同样剂量青毒素300 万U·kg-1腹腔注射,观察大鼠行为表现及EEG改变.结果氟桂利嗪能明显降低青霉素致癎大鼠癎性发作程度,明显缩短癎性发作持续时间,显著延长癎性发作的潜伏期,明显提高存活率;明显延长大脑皮质、海马癎性放电潜伏期,缩短其持续时间,明显减少癎性放电的数量.结论氟桂利嗪对青霉素致癎大鼠的癎性行为和大脑皮质、海马的癎性电活动均有抑制作用.     

青霉素致(癎)大鼠海马细胞内Ca2+浓度变化与神经元单位放电的关系

目的 探讨癫(癎)大鼠海马细胞内Ca2+浓度变化和神经元单位放电的关系.方法36只Wistar雄性健康大鼠分为3组.癫(癎)模型组用青霉素钠600万U/kg腹腔注射制作成癫(癎)模型;癫(癎)预处理组在制作模型前用盐酸氟桂利嗪按20 mg/kg间隔12 h灌胃2次,第2次给药后2 h用青霉素钠600万U/kg腹腔注射制作模型.3组实验大鼠均在记录单位放电后处死,取双侧海马应用新一代钙荧光指示剂Fluo-3-AM通过流式细胞分析仪测定细胞内Ca2+荧光浓度.结果 正常对照组大鼠共记录到24个单位海马神经元放电,海马细胞内Ca2+平均荧光浓度为37.12±5.08;癫(癎)模型组共记录到78个单位海马神经元放电,海马细胞内Ca2+平均荧光浓度为52.04±6.75;癫(癎)预处理组共记录到47个单位海马神经元放电,海马细胞内Ca2+平均荧光浓度为37.79±3.09.Ca2+平均荧光值和海马单位放电个数相关系数r=0.737,P＜0.01.结论 青霉素致病大鼠海马细胞内Ca2+浓度变化与海马神经元单位放电呈正相关关系.

Abstract：

Objective To investigate the relationship between changes in Ca2+ concentration and unit discharge in the hippocampal neurons of epileptic rats.Methods Thirty-six healthy male Wistar rats were divided into three groups. Rats of the epilepsy group received an intraperitoneal injection of benzylpenicllin sodium at 6 million unit/kg; Rats of the epilepsy pretreatment group received 20 mg/kg of flunarizine at 14 and 2 hours before injection of benzylponicllin;the control group of rats received an intraperitoneal injection of normal saline.Three groups of rats were euthanized after recording of the unit discharge,and bilateral hippocampal cells were obtained to measure the cellular concentration of Ca2+ fluorescence using the new generation Ca2+ fluorescent dye Fluo-3-AM and flow cytometry.Results (1) A total of 24 units of hippocampal discharges were recorded in the control group.The average concentration Ca2+ fluorescence of the hippocampal neurons was 37.12±5.08.(2)A total of 78 units of hippocampal discharges were recorded in the epilepsy group.The average concentration of Ca2+fluorescence of the hippocampal neurons was 52.04±6.75.(3)A total of 47 units of hippocampal discharges were recorded in the epilepsy pretreatment group. The average concentration of Ca2+ fluorescence of the hippocampal neurons was 37.79±3.09.The correlation coefficient between the average concentration of Ca2+ fluorescence of the hippocampal neurons and the number of units of hippocampal discharge ( r=0.737,P＜0.01).Conclusion There is a positive correlation between changes in average concentration of Ca2+ fluorescence of the hippocampal neurons and the numbers of units of hippocampal discharge.     

氟桂利嗪对杏仁核点燃鼠海马Bax mRNA表达的影响

目的:观察氟桂利嗪对杏仁核点燃鼠癎性发作及海马促凋亡基因Bax mRNA表达的影响。方法:建立杏仁核点燃模型,予不同剂量氟桂利嗪灌喂点燃鼠。原位杂交法检测鼠脑海马Bax mRNA表达,图像分析软件测量阳性细胞平均吸光度。结果:正常大鼠海马存在少量Bax mRNA表达阳性细胞,点燃鼠海马各区Bax mRNA表达阳性细胞数及平均吸光度增加,氟桂利嗪处理后平均吸光度下降与剂量有关。结论:氟桂利嗪具有抗癫癎效应和拮抗点燃鼠海马Bax mRNA表达的作用。     

甲氧明对青霉素致癎大鼠发作行为与皮层脑电图的影响

目的探讨α1受体激动剂甲氧明对青霉素致癎大鼠发作行为学与皮层脑电图的影响。方法建立大鼠青霉素点燃模型,分别腹腔注射或海马注射甲氧明,按照改良racine分级标准,观察对大鼠发作行为学的影响以及皮层脑电图的变化。结果甲氧明腹腔注射预处理组达到I级的潜伏期(32.5±12.4)min比生理盐水组(15.2±8.1)min明显延长;甲氧明组racine分级均在Ⅱ级或Ⅱ级以下,生理盐水组全部达到Ⅳ级(P<0.01)。海马注射甲氧明预处理组脑电图癎性放电潜伏期(24′6″±5′53’″)较空白组(8′41″±1′13″)和生理盐水组(6′31″±1′43″)明显延长;生理盐水组与未预先处理组无明显统计学差异。与腹腔注射生理盐水相比,腹腔注射甲氧明对脑电图癎性放电改变没有统计学差异(P>0.05),海马注射甲氧明组与海马注射生理盐水组有明显统计学差异(P<0.01),海马注射甲氧明可以减少性放电。结论甲氧明延缓青霉素诱导癫癎的发展进程并降低癎性发作强度;甲氧明海马注射抑制青霉素癫癎模型皮层脑电图性放电程度;中枢α1肾上腺素受体参与青霉素诱导癫癎的抑制作用。     

低剂量伽玛刀照射癫癎大鼠脑神经元的超微结构研究

目的探索伽玛刀治疗原发性癫的细胞学机理。方法建立大鼠皮质青霉素局灶性癫癎模型,将SD大鼠随机分为实验组、实验对照组和对照组。照射周边剂量12 Gy, 等剂量曲线为50%。分别于0.5 h~2个月后取靶区皮质及海马标本制备光镜、常规透射电镜样品。结果癫癎模型鼠可见较多凋亡神经元,而癫癎模型鼠经低剂量伽玛刀照射后同时程的神经元改变较轻微,凋亡细胞少见。结论凋亡参与了青霉素致癫癎发作后海马神经元的死亡过程,低剂量伽玛刀照射对抑制神经元的死亡过程有重要作用。     

Sombati癫癎细胞模型电压依赖性钾电流的变化

目的：采用全细胞膜片钳记录技术研究Sombati癫癎细胞模型电压依赖性K＋电流的变化。方法：取SD新生乳鼠双侧海马,体外原代培养海马神经元,培养至第9天的部分海马神经元经无镁液处理3h制备癫癎细胞模型,采用全细胞膜片钳技术分别记录正常组（未经无镁液处理的海马神经元）和致癎组（经无镁液处理3h后更换为正常维持培养液的海马神经元）海马神经元的电压依赖性外向K＋电流。结果：致癎组外向K＋电流比正常组增大,峰值电流由（596.62±79.23）pA增至（978.68±53.23）pA,两组间比较差异有统计学意义（P=0.000）。与正常组相比,致癎组的I-V曲线明显左移,I-V曲线形态无显著改变。结论：Sombati癫癎细胞模型中,电压依赖性外向K＋电流显著增加可能是癫癎细胞模型癎性放电后为了保持细胞稳态的代偿性保护作用。     

生酮饮食对海人酸点燃癫癎模型大鼠海马神经元保护作用研究

目的探讨生酮饮食对海人酸点燃癫癎模型大鼠海马神经元的保护作用。方法经海人酸制备SD大鼠癫癎模型,分别给予生理盐水+正常膳食(C组)、生理盐水+生酮饮食(K组)、海人酸+正常膳食(E组)和海人酸+生酮饮食(EK组),连续观察21 d后记录不同处理组大鼠体重、观察Ⅳ或Ⅴ级癫癎发作频率和持续时间,并通过HE染色和Nissl染色计数E组和EK组大鼠海马CA3区正常锥体神经元数目。结果 C组和K组大鼠均无癫癎发作,且海马CA3区锥体神经元数目正常。E组和EK组大鼠在观察过程中均出现Ⅳ或Ⅴ级癫癎发作,但EK组大鼠在饲养第21天时与E组相比,癫癎发作频率减少[(17.90±4.12)次对(30.50±4.40)次,P=0.000]、发作持续时间缩短[(212.70±17.75)s对(335.00±14.21)s,P=0.000],差异有统计学意义;EK组海马CA3区正常锥体神经元数目与E组相比增加[(117.67±7.51)个对(71.33±6.11)个,P=0.000],差异亦有统计学意义。结论生酮饮食对海人酸点燃癫癎模型大鼠海马神经元具有保护作用。     

喹啉对癫(癎)大鼠海马神经元连接蛋白36表达的影响

目的:探讨喹啉对癫癎大鼠海马神经元连接蛋白36(Cx36)表达的影响.方法:64只SD大鼠随机分为正常对照组、癫癎模型组、地西洋治疗组和喹治疗组,每组16只大鼠.采用氯化锂-匹罗卡品诱导制作癫癎大鼠模型,地西泮治疗组子以1mg/kg地西泮治疗,喹啉治疗组予以60mg/kg喹啉治疗.术后分别采用Racine评分和脑电图检查判断癫癎发作情况.分别用免疫荧光染色法、Western blot法检测各组大鼠术后2h、4h时海马神经元Cx36的表达.结果:与正常对照组比较,癫癎模型组和地西泮治疗组大鼠术后2h、4h时海马神经元Cx36表达水平显著升高(均P<0.01).癫癎模型组和地西泮治疗组大鼠术后2h、4h时海马神经元Cx36表达水平比较差异无统计学意义.与癫癎模型组及地西泮治疗组比较,喹啉治疗组大鼠术后2h、4h时海马神经元Cx36表达水平显著降低(均P<0.01).结论:癫癎大鼠海马神经元Cx36表达水平升高,喹啉能抑制这一变化.     

活化素A对致痫小鼠行为、脑电及海马神经元损伤的影响

目的观察重组人活化素A(rhACT)对匹鲁卡品(PC)致癎小鼠行为、脑电及海马神经元损伤的影响.方法利用脑立体定位手段将rhACT注入侧脑室,1 h后腹腔注射PC.采用发作程度评分、脑电记录观察rhACT对癫癎发作与放电的影响;利用尼氏染色及组织原位凋亡检测观察rhACT对注射PC后24及48h海马神经元损伤的影响.结果预先脑室注射rhACT后PC诱导的癫癎发作显著减轻,癎样放电明显受抑制;24及48h海马神经元未见明显损害.结论rhACT可能有抗K诱导的癫癎发作及保护海马神经元的作用.     

托吡酯治疗儿童交替性偏瘫的疗效观察

目的 观察托吡酯(TPM)治疗儿童交替性偏瘫(AHC)的临床疗效.方法 对氟桂利嗪等药物治疗无效的6例AHC患儿应用TPM治疗,观察TPM治疗后偏瘫及伴随的癫(癎)和偏头痛的发作频率、持续时间及严重程度的变化.结果 TPM治疗6个月后患儿偏瘫发作频率降低76.4%、持续时间减少80.2%,严重程度亦降低.癫(癎)发作频率和持续时间分别降低84.5%和75.5%,偏头痛发作频率和持续时间分别降低77.5%和76.4%.结论 TPM对氟桂利嗪等治疗无效AHC患儿具有较好的疗效.     

Penicillin-induced epilepsy model in rats: dose-dependant effect on hippocampal volume and neuron number

This study was designed to evaluate the penicillin-induced epilepsy model in terms of dose-response relationship of penicillin used to induce epilepsy seizure on hippocampal neuron number and hippocampal volume in Sprague-Dawley rats. Seizures were induced with 300, 500, 1500 and 2000IU of penicillin-G injected intracortically in rats divided in four experimental groups, respectively. Control group was injected intracortically with saline. Animals were decapitated on day 7 of treatment and brains were removed. The total neuron number of pyramidal cell layer from rat hippocampus was estimated using the optical fractionator method. The volume of same hippocampal areas was estimated using the Cavalieri method. Dose-dependent decrease in hippocampal neuron number was observed in three experimental groups (300, 500 and 1500IU of penicillin-G), and the effects were statistically significant when compared to the control group (P<0.009). Dose-dependent decrease in hippocampal volume, on the other hand, was observed in all three of these groups; however, the difference compared to the control group was only statistically significant in 1500IU of penicillin-G injected group (P<0.009). At the dose of 2000IU penicillin-G, all animals died due to status seizures. These results suggest that the appropriate dose of penicillin has to be selected for a given experimental epilepsy study in order to demonstrate the relevant epileptic seizure and its effects. Intracortical 1500IU penicillin-induced epilepsy model may be a good choice to practice studies that investigate neuroprotective mechanisms of the anti-epileptic drugs.     

大鼠脑出血早期应用他莫西芬的治疗作用

目的:本研究探讨大鼠实验性脑出血（ICH）早期应用不同剂量他莫西芬（Tam）对脑损伤的保护作用。方法:雄性SD大鼠56只,予右侧基底节注射100μL自体动脉血制作ICH模型,并分为3大组。①24h脑水含量及病理观察组（各亚组均n=6）:大鼠在ICH后2 h分别接受不同剂量Tam(Tam 2.5 mg·kg^-1组、Tam 5 mg·kg^-1组)和4%DMSO生理盐水（24 h对照组）腹腔注射,24 h后处死进行脑水含量及病理观察。②72 h脑水含量观察组（各亚组均n=6）:大鼠在ICH后2h和24h分别接受不同剂量Tam(72h Tam2.5mg·kg^-1+2.5mg·kg^-1组、72hTam2.5mg.kg^-1+5mg·kg^-1组、72h Tam 5mg.kg^-1+5mg·kg^-1组)和4%DMSO生理盐水（72 h对照组）腹腔注射,于术后72 h处死测量脑水含量。③28 d影像学及病理学观察组:大鼠在ICH后2和24h分别2次给予tam(28d Tam 5mg.kg^-1+5mg,kg^-1组)（n=6）,4%DMSO生理盐水（28 d对照组）（n=8）腹腔注射,分别在术后1、7、14和28d随访MRI和行为学变化,并在第28天处死进行组织学检查。结果:Tam5 mg·kg^-1能明显减轻ICH后3 d时脑水肿（P<0.05）,改善术后行为学评分（P<0.05）,并能明显减轻ICH术后28 d同侧尾状核的脑萎缩（P<0.01）,但MRI提示2例大鼠出现幕上脑室异常扩大。结论:Tam作为选择性雌激素受体调节剂,在ICH后有明显的神经保护作用,但发生了脑积水的不良反应,需要进一步的研究。     

耳甲腔电刺激对药物难治性癫痫大鼠发作及学习记忆影响的研究

目的探讨耳甲腔刺激对药物难治性癫痫大鼠痫性发作及学习记忆的影响,明确特定频率电刺激癫痫大鼠耳甲腔引起的行为学改变。方法 120只Wistar雄性大鼠氯化锂-匹鲁卡品制备惯常发作的颞叶癫痫大鼠,苯巴比妥诱导建立并筛选药物难治性癫痫大鼠50只,随机分为刺激组(20只)、假刺激组(20只)、非刺激组(10只)。按特定参数进行刺激,刺激参数设定为:电流强度1mA,波宽500μs,频率20Hz,刺激时间30s,间歇5分钟,10h/d(08:00~18:00),连续刺激4周。24小时视频脑电监测大鼠发作情况,刺激结束后,进行Morris水迷宫实验,观察大鼠学习记忆能力变化。三组大鼠断头取脑后切片,HE染色,镜下观察。结果成功建立并筛选药物难治性癫痫大鼠,耳甲腔刺激组大鼠癫痫发作次数明显下降,非刺激组和假刺激组大鼠癫痫情况无明显改变。三组间癫痫发作情况差异有统计学意义(P0.01);非刺激组和假刺激组刺激前后癫痫发作率无统计学意义(P0.05)。与假刺激和非刺激组相比,刺激组大鼠定向航行试验潜伏期明显缩短(P0.01),定向航行试验中刺激组大鼠穿越目标象限频次及目标象限停留时间均显著长于其他两组(P0.01)。HE染色发现假刺激组和非刺激组海马神经元明显变性、减少,刺激组则较轻。结论电刺激耳甲腔不仅能够显著抑制大鼠痫性发作,同时能改善因反复痫性发作而受损的学习记忆能力。     

Effects of Low‐Frequency Hippocampal Stimulation on Gamma‐Amino Butyric Acid Type B Receptor Expression in Pharmacoresistant Amygdaloid Kindling Epileptic Rats

Objective: To observe the effect of low‐frequency hippocampal stimulation on gamma‐amino butyric acid type B (GABA‐B) receptor expression in hippocampus pharmacoresistant epileptic rats. Materials and Methods: Sixteen pharmacoresistant epileptic rats were selected by testing their seizure response to phenytoin and phenobarbital, and they were randomly divided into a pharmacoresistant control group (PRC group, eight rats) and a pharmacoresistant stimulation group (PRS group, eight rats). Another 16 pharmacosensitive epileptic rats were served as control, also divided randomly into a pharmacosensitive control group (PSC group) and a pharmacosensitive stimulation group (PSS group). A stimulation electrode was implanted into the rats' hippocampus in the four groups. Low‐frequency hippocampal stimulation was administered twice per day for two weeks. Following these weeks of stimulation, GABA‐B receptor‐positive neurons were counted and the gray values of GABA‐B receptor expression in the rats' hippocampal tissues were measured. Results: The amygdale stimulus‐induced epileptic seizures were decreased significantly in the PRS group compared with the PRC group. The parameters of the amygdale after discharge also were improved after hippocampal stimulation. Simultaneously, the GABA‐B receptor‐positive neurons increased and the GABA‐B expression gray values decreased markedly in the PRS group compared with the PRC group. The same phenomenon also was observed between the PSS group and the PSC group. However, no significant difference was found in the GABA‐B receptor‐positive neurons and the gray values of GABA‐B between the PRS group and the PSC group. Conclusions: The low‐frequency hippocampal stimulation may inhibit the amygdale stimulus‐induced epileptic seizures and the after discharges. The antiepileptic effects of the hippocampal stimulation may be achieved partly by increasing the expression of the GABA‐B receptor.     

Prevention of seizures and reorganization of hippocampal functions by transplantation of bone marrow cells in the acute phase of experimental epilepsy

In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine's seizure severity scale. All of the rats in the saline-treated epileptic control group developed SRS, whereas none of the BMC-treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long-term chronic phase (120 days after transplantation), only 25% of BMC-treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral-CA1 synapses, long-term potentiation was preserved in BMC-transplanted rats compared to epileptic controls. The donor-derived GFP⁺ cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network.     

Minimal latency to hippocampal epileptogenesis and clinical epilepsy after perforant pathway stimulation-induced status epilepticus in awake rats

Hippocampal epileptogenesis is hypothesized to involve secondary mechanisms triggered by initial brain injury. Chemoconvulsant-induced status epilepticus has been used to identify secondary epileptogenic mechanisms under the assumption that a seizure-free, preepileptic "latent period" exists that is long enough to accommodate delayed mechanisms. The latent period is difficult to assess experimentally because early spontaneous seizures may be caused or influenced by residual chemoconvulsant that masks the true duration of the epileptogenic process. To avoid the use of chemoconvulsants and determine the latency to hippocampal epileptogenesis and clinical epilepsy, we developed an electrical stimulation-based method to evoke hippocampal discharges in awake rats and produce hippocampal injury and hippocampal-onset epilepsy reliably. Continuous video monitoring and granule cell layer recording determined whether hippocampal epileptogenesis develops immediately or long after injury. Bilateral perforant pathway stimulation for 3 hours evoked granule cell epileptiform discharges and convulsive status epilepticus with minimal lethality. Spontaneous stage 3-5 behavioral seizures reliably developed within 3 days poststimulation, and all 72 spontaneous behavioral seizures recorded in 10 animals were preceded by spontaneous granule cell epileptiform discharges. Histological analysis confirmed a reproducible pattern of limited hippocampal and extrahippocampal injury, including an extensive bilateral loss of hilar neurons throughout the hippocampal longitudinal axis. These results indicate that hippocampal epileptogenesis after convulsive status epilepticus is an immediate network defect coincident with neuron loss or other early changes. We hypothesize that the latent period is directly related and inversely proportional to the extent of neuron loss in brain regions involved in seizure initiation, spread, and clinical expression.     

Pathophysiology of generalized photosensitive epilepsy in the cat

Feline generalized penicillin-induced epilepsy is a reliable experimental model of epileptic photosensitivity. Binocular photic stimulation at 4-8 flashes/s consistently triggers generalized, bilaterally synchronous spike-and-wave discharges in cats submitted to long-term intramuscular penicillin administration at low dosage (50,000-150,000 IU/kg). The photically induced epileptic activity is first and mainly recorded from the cerebral cortex as compared with the lateral geniculate (GL) body, therefore supporting a cortical onset of epileptic photosensitivity. At this low penicillin dosage, only minimal spontaneous spike-and-wave activity is recorded. Bilateral GL stimulation is more effective than binocular photic stimulation in triggering spike-and-wave discharges, whereas unilateral GL stimulation is grossly ineffective. This observation implies a role of bilateral specific visual thalamocortical volleys in the genesis of epileptic photosensitivity. Five of 12 randomly selected cats receiving long-term penicillin exhibited spontaneous epileptic photosensitivity, a finding that suggests an underlying genetic predisposition of the feline species to this condition.     

唑尼沙胺对戊四氮致痫小鼠认知功能的影响

目的探讨唑尼沙胺(ZNS)对癫痫小鼠的认知功能影响及抗癫痫作用。方法利用戊四氮(PTZ)致痫小鼠模型,通过Morris水迷宫实验、神经元特异性烯醇化酶(NSE)及海马组织形态学的改变,观察ZNS对癫痫小鼠的认知功能影响及抗癫痫作用。结果正常组小鼠无惊厥发作,血清NSE水平在正常范围,海马组织结构正常;癫痫组惊厥出现时间早,发作程度重,血清NSE水平明显高于其它两组,海马组织结构紊乱、疏松;ZNS组惊厥出现时间晚,发作程度轻,血清NSE水平略高于正常组而显著低于癫痫组,海马组织结构无显著变化。结论 ZNS有明确抗癫痫作用,通过控制癫痫发作,有效的改善致痫小鼠的认知功能。     

Effects of A1 receptor agonist/antagonist on spontaneous seizures in pilocarpine-induced epileptic rats

Adenosine is an endogenous anticonvulsant that activates pre- and postsynaptic adenosine A₁ receptors. A₁ receptor agonists increase the latency for the development of seizures and status epilepticus following pilocarpine administration. Although hippocampal adenosine is increased in the chronic phase of the pilocarpine model, it is not known whether the modulation of A₁ receptors may influence the frequency of spontaneous recurrent seizures (SRS). Here, we tested the hypothesis that the A1 receptor agonist RPia ([R]-N-phenylisopropyladenosine) and the A1 antagonist DPCPX (8-Cyclopentyl-1,3-dipropylxanthine) administered to chronic pilocarpine epileptic rats would respectively decrease and increase the frequency of SRS and hippocampal excitability. Four months after Pilo-induced SE, chronic epileptic rats were video-monitored for the recording of SRS before (basal) and after a 2-week treatment with RPia (25 μg/kg) or DPCPX (50 μg/kg). Following sacrifice, brain slices were studied with electrophysiology. We found that rats given RPia had a 93% nonsignificant reduction in the frequency of seizures compared with their own pretreatment baseline. In contrast, the administration of DPCPX resulted in an 87% significant increase in seizure rate. Nontreated epileptic rats had a similar frequency of seizures along the study. Corroborating our behavioral data, in vitro recordings showed that slices from animals previously given DPCPX had a shorter latency to develop epileptiform activity, longer and higher DC shifts, and higher spike amplitude compared with slices from nontreated Pilo controls. In contrast, smaller spike amplitude was recorded in slices from animals given RPia. In summary, the administration of A1 agonists reduced hippocampal excitability but not the frequency of spontaneous recurrent seizures in chronic epileptic rats, whereas A1 receptor antagonists increased both.