Prenatal nicotine exposure increased duration of nicotine-induced analgesia in adult rats

The effect of prenatal exposure to nicotine on nicotine-induced analgesia was studied in rats. The analgesic effect of a single dose of nicotine (1 mg/kg SC) was measured by the tail-flick technique, and two subsequent studies were carried out. In the first study, 7-month-old male rats, born to dams chronically treated with nicotine during pregnancy (NIC), exhibited prolonged nicotine-induced analgesia compared to matched controls. The second study was designed to explore whether rats prenatally exposed to nicotine (NIC rats) are born with an increased sensitivity to nicotine and whether there is any sex difference. The analgesic effect of nicotine was tested on control and NIC rats of both sexes once a month from 2 to 7 months of age. At an early age, male but not female NIC rats, exhibited shorter analgesic responses to nicotine than did the matched controls. With increasing age, however, the duration of nicotine analgesia began to be prolonged in NIC rats of both sexes. Significant differences between control and NIC rats were found at the age of 6 and 7 months, in both sexes. Thus, rats prenatally exposed to nicotine are not born with an increased sensitivity to the analgesic effect of a single dose of nicotine. This phenomenon develops later, during the course of life, independently of gender.     

Effect of calcitonin on total body bone mineral contents of experimental osteoporotic rats determined by dual photon absorptiometry

Summary Total body bone mineral (TBBM) content in rats was measured by dual photon absorptiometry (DPA). TBBM showed significant increases over 4 weeks in control groups with significant bone loss over the same time in prednisolone-injected rats on low calcium feed. Daily injections of calcitonin significantly reduced loss of bone mass. Both prednisolone- and prednisolone-calcitonin-injected groups showed significantly elevated serum alkaline phosphatase with the prednisolone-calcitonin group also exhibiting elevated serum calcium and phosphate levels, confirming the impact of the experimental protocol. TBBM measured by DPA in all groups correlated well (r=0.928,P<0.001 n=20) with the total ash weight suggesting that the method reflects total skeletal mineral content in the small animal. TBBM measurement by DPA proves well-suited to monitoring bone mineral in a small animal experimental setting.     

Self-administration in baboons and the discriminative stimulus effects in rats of bupropion,nomifensine, diclofensine and imipramine

The behavioral effects of the antidepressants nomifensine, diclofensine, bupropion, and imipramine were examined using a cocaine substitution drug self-administration procedure in baboons and a cocaine drug discrimination procedure in rats. Intravenous self-administration of the antidepressants was examined in baboons under conditions in which baseline responding was maintained by intravenous injections of cocaine HCl (0.32 mg/kg/injection). Drug was available under a fixed-ratio 80-response or 160-response schedule of intravenous injection. Each drug injection was followed by a 3-h time-out allowing a maximum of eight injections per day. The antidepressants or their vehicles were substituted for cocaine for a period of 15 days, followed by a return to the cocaine baseline. Nomifensine, diclofensine, and bupropion all maintained self-administration behavior at levels above those maintained by their respective vehicles. Some doses of nomifensine, diclofensine, and bupropion maintained levels of behavior similar to those maintained under baseline cocaine conditions. High doses of imipramine maintained levels of behavior above those maintained by its vehicle, but the amount of behavior maintained under these conditions was extremely small. In a second experiment rats were trained to discriminate 32 µmol/kg cocaine (IP 10 min presession) from no drug in a two-lever food reinforced drug discrimination procedure in which responding on one lever was reinforced following ten consecutive responses when the session was preceded by cocaine administration, while responding on the other lever was similarly reinforced in the absence of cocaine pretreatment. Cocaine, nomifensine, diclofensine, and bupropion all dose-dependently occasioned cocaine-appropriate responding. Imipramine did not occasion cocaine-appropriate responding over a range of behaviorally active doses.     

Competition for sucrose-pellets in triads of male wistar rats: effects of acute and subchronic chloridazepoxide

Within triads of male Wistar rats, some animals almost completely abstain from competition for palatable sucrose pellets (so-called poor-performing rats), whereas other rats consistently win the competition (so-called high-performing rats). Subchronic (5 mg/kg; 5 consecutive days), but not acute (0.1–20 mg/kg), treatment with chlordiazepoxide temporarily helped poor-performing rats to behave more competitively. This finding, considered together with parallel studies (using high-performing rats), suggested that chloridazepoxide's beneficial effect was only demonstrable when the poor-performing rats had become tolerant to the drug's initial sedative effect.     

Modulation of Rat Striatal Glutamatergic Response in Search for New Neuroprotective Agents: Evaluation of Melatonin and Some Kynurenine Derivatives

Melatonin attenuates the excitatory response of striatal neurons to sensorimotor cortex (SMCx) stimulation, which may be the basis for its neuroprotective role. Searching for new compounds with melatonin-like properties, the effects of several kynurenine derivatives in the response of the rat striatum to SMCx stimulation were studied using electrophysiological and microiontophoretical techniques. Melatonin iontophoresis (−100 nA) significantly attenuated the striatal excitatory response in 89.4% of the recorded neurons, showing excitatory properties in the other 10.6%. Compound A [2-acetamide-4-(3-methoxyphenyl)-4-oxobutyric acid] (−100 nA) displayed similar attenuating effects (86.7% of neurons inhibited vs. 13.3% excited). Compound B [2-acetamide-4-(2-amine-5-methoxyphenyl)-4-oxobutyric acid] (−100 nA) was more potent than melatonin itself to attenuate the excitatory response in 100% of the recorded neurons. Compound C [2-butyramide-4-(3-methoxyphenyl)-4-oxobutyric acid] (−100 nA) significantly increased the excitatory response in 84.2% of the recorded neurons, showing attenuating effects on the other 15.8% of the neurons. Interestingly, compound C iontophoresis excited the neurons in which melatonin had attenuating properties, whereas it inhibited the neurons showing excitatory responses to melatonin. These data suggest melatonin inverse agonist properties for compound C. Also, the effects of compounds B and C appeared immediately after they were iontophoretized, whereas both melatonin and compound A onset latencies were longer (2–4 min). The lack of latency shown by these melatonin analogs points to the possibility that melatonin itself was metabolized before producing its effects on striatal neurons. The results show a family of structurally-related melatonin analogs that may open new perspectives in search for new neuroprotective agents, including its clinical potentiality.     

人参总皂甙对不完全性脑缺血后海马CA1区NOS阳性神经元表达的影响

目的探讨人参总皂甙(GS)对不完全性脑缺血及再灌注不同时间后海马CA1区一氧化氮合酶(NOS)的影响及对神经元的保护作用.方法用双侧颈总动脉夹闭加放血的方法制成大鼠不完性脑缺血及再灌注模型,以还原烟酰胺腺嘌呤二核苷酸脱氢酶(NADPH-d)组织化学方法观察缺血及再灌注后海马CA1区NOS阳性神经元变化及GS对其的影响.结果单纯缺血组海马CA1区在缺血30min时NOS阳性细胞数最高(44.5±7.42),为假手术组2倍,再灌注2h、12h、24h、3d后逐渐下降,5d时恢复正常水平(21.12±3.50),缺血再灌注3d、5d时出现神经细胞损伤.GS能抑制缺血30min及再灌注各时程中NOS阳性神经元数量变化,并能预防缺血再灌注后迟发的神经元损害.结论GS对大鼠不完全性脑缺血及再灌注不同时程后海马CA1区NOS的异常表达有抑制作用,对神经元的保护作用.     

非糖皮质激素的免疫抑制方案对同种异体移植胰岛的保护作用

目的　评价非糖皮质激素的免疫抑制方案对防止大鼠同种异体胰岛移植排斥反应的效果。方法　大鼠同种异体胰岛移植后 ,分别应用他克莫司 (FK5 0 6 ) 霉酚酸酯 (MMF)和FK5 0 6 MMF 泼尼松 (Pred)行免疫抑制治疗两周 ,并设对照组 ,动态观察受者血糖、胰岛素及C肽变化 ,并作移植部位的形态学检测。结果　FK5 0 6 MMF组和FK5 0 6 MMF Pred组与对照组相比 ,移植胰岛存活时间明显延长 ,移植后 2个月在受者肝汇管区可见较多形态完整的胰岛细胞。FK5 0 6 MMF组维持术后正常血糖、胰岛素及C肽的时间超过 6 0d ,而FK5 0 6 MMF Pred组与前者比较 ,分泌C肽较少 (P <0 .0 5 ) ,血糖维持在较高水平 (P <0 .0 1) ,胰岛素水平两组差异无显著性。FK5 0 6 MMF Pred组停药两周以后的血糖水平较用药期间、停药两周内有明显降低 (P <0 .0 5 ) ,胰岛素和C肽分泌有所增多 ,但差异无显著性。结论　应用FK5 0 6 MMF和FK5 0 6 MMF Pred均有很强的免疫抑制效应 ,但糖皮质激素对胰岛细胞有毒性作用。小剂量FK5 0 6与MMF联用对移植胰岛细胞有较强的保护作用。     

葡甘聚糖对大鼠实验性脂肪肝的预防和治疗作用

目的 :为探讨葡甘聚糖对脂肪肝大鼠高脂血症的影响。方法 :Wistar大鼠随机分为 6组 ,即正常对照组 (n =8、C) ,模型组 (n =8、M) ,易善力预防组 (n =8、A1)、葡甘聚糖预防组 (n =9、B1) ,易善力治疗组 (n =11、A2 )和葡甘聚糖治疗组 (n =9、B2 )。检测处理 2周和 4周末血清肝脏酶学 (ALT、AST)、血脂 (TG、TC)水平和肝组织脂肪变性程度。结果 :与C组比较 ,M组血清生化ALT、AST水平显著升高 [(2 5 6± 14 4 .7)U L ,(410 .9± 12 0 .5 )U L](P<0 .0 1)。与M组相比 ,B1、A2、B2组ALT水平显著下降 [(15 0 .3± 5 8.4 )U L ,(76± 6 5 .1)U L ,(5 3.2± 5 3.1)U L](P <0 .0 5 ) ,而AST水平无明显降低 (P >0 .0 5 ) ,甚或升高。与C组比较 ,M组血清脂质TC、TG显著升高 [(1.5±0 .90 )mmol L ,(3.5± 0 .4 1)mmol L]]。与M组相比较 ,A1、B1组血清TG、TC水平无明显下降 ,分别为 [(1.6 0± 1.4 1)mmol L ,(3.4 0± 0 .4 5 )mmol L],和 [(0 .99± 0 .5 5 )mmol L ,(3.6 0± 0 .38mmol L) ](P >0 .0 5 ) ,而A2组和B2组显著降低 (P <0 .0 5 ) ,分别为 [(0 .5 3± 0 .5 5 )mmol L ,(3.10± 0 .36 )mmol L]和 [(0 .4 7± 0 .36 )mmol L ,(2 .86± 0 .10mmol L) ]。肝病理组织学检查发现 ,M组肝小叶内肝细胞发生中、重     

犬烟雾吸入性损伤早期肺洗出液灌注大鼠肺所致损伤的研究

目的　研究犬烟雾吸入性损伤早期肺洗出液的生物学活性。　方法　获取犬急性烟雾吸入性损伤早期肺洗出液及正常犬肺洗出液。将Wistar大鼠随机分为A(2 8只 )、B(2 9只 )、C(37只 )组 ,每组各取 7只不作处理作为正常对照 ,其余大鼠肺部作如下处理 :A组注入等渗盐水 ,B组注入正常犬肺洗出液 ,C组注入致伤犬肺洗出液。处死各组中正常对照大鼠 ,并于灌注后 4、12、2 4h处死灌注大鼠 ,观察各组大鼠处死前的存活情况、处死后双肺大体变化及组织病理学改变。检测肺组织匀浆中 6 酮 前列腺素F1α/血栓素B2 (PGF1α/TXB2 )、肿瘤坏死因子α(TNF α)、髓过氧化物酶 (MPO)含量及肺毛细血管通透性。　结果　A、B组大鼠处死前均存活 ,C组大鼠非处死死亡 9只。犬吸入性损伤早期肺洗出液可引起大鼠肺产生类似于烟雾吸入性损伤样的病理变化。A、B组大鼠灌注后肺组织PGF1α/TXB2 均有升高倾向 ;C组大鼠灌注后PGF1α/TXB2 逐渐降低 (P <0.0 1),A、B组灌注后肺组织TNF α、MPO含量均无明显变化 (P >0.0 5 ),C组灌注后 4h肺组织TNF α、MPO含量显著增加 ,分别为 (1.0 2± 0 .0 4 )ng/ml、(1.0 1± 0.0 9)U/g肺组织湿重 ,随后下降 (P <0.0 5～ 0.0 1)。肺灌注后4hC组大鼠肺组织毛细血管通透性高于A、B组 (P <0.0 1)。结论　犬     

Postnatal formation of the blood-testis barrier in the rat with special reference to the initiation of meiosis

Summary Postnatal formation of the Blood-Testis Barrier (BTB) in the rat was studied by either fixation in hypertonic fixative or employing lanthanum tracer. After 15 days of age, meiosis has reached different stages of spermatogenesis in differnt zones of the seminiferous cords. Only in those parts where germ cells are in the pachytene stage of meiosis do Sertoli cells form an effective barrier or tight compartment. Between 16 and 19 days of age, final formation of the BTB, which is to be found in the adult rat testis, occurs by zygotene and then leptotene stages successively entering the tight compartment. Thus, formation of a BTB by Sertoli cells does not occur synchronously along the length of the seminiferous cord but in accordance with the stage of meiosis of the associated germ cells.