雷公藤多甙与棉酚合用对雄大鼠生育力的影响

本研究探讨雷公藤多甙(GTW)与棉酚合用对雄大鼠生育力的影响。SD雄大鼠用棉酚及GTW各6 mg/kg/d,灌胃给药,每周6日,共11周。10只用药动物全部不育,附睾精子密度和活率也明显下降,而体重增长如常,性行为存在。睾丸光镜下结构绝大多数无明显异常,血清睾酮水平正常,副性腺重量无明显变化。停药6周后生育力恢复。在相同剂量下,单用GTW或棉酚均无抗生育效果。表明两药合用有相加作用,为减少棉酚和GTW副作用提供一条可能途径。     

胎脑组织移植对额叶皮质损伤后基底前脑胆碱能神经元变性的影响

目的：观察胎脑组织移植对额叶皮质损伤后大鼠基底前脑胆碱能神经元变性的影响。方法：用外科手术破坏大鼠双侧额叶皮质8d后，将胎脑组织移植到预制脑创腔内。3个月后，用Y型迷宫检测动物的学习、记忆机能，用组织化学方法检测基底前脑含乙酰胆碱脂酶（AChE)活性神经元，并与对照组比较。结果：双侧额叶皮质损伤后动物的学习、记忆能力明显下降，基底前脑胆碱能神经元明显减少，与正常组比较，差异有显著性（P＜0．05）和差异有极显著性（P＜0．01）。胎脑组织移植后3个月，双侧额叶皮质受损动物的学习、记忆机能明显改善，基底前脑胆碱能神经元数量明显增加，与对照组比较，差异有性（P＜0．05）。结论：胎脑组织移植可有效地预防双侧额叶皮质受损大鼠的学习、记忆机能的下降和基底前脑胆碱能神经元数量的减少。     

EGCG对大鼠肾脏缺血再灌注损伤的保护作用

目的研究表绿茶活性成分没食子儿茶素-3-没食子酸酯（epigallocatechin gallate，EGCG）对大鼠肾脏缺血再灌注损伤是否具有保护作用。方法将12只Lewis大鼠随机分为2组：（1）实验组大鼠7只，于肾缺血后的再灌注期将10mg／kg的EGCG置于2ml生理盐水中静脉注射；（2）对照组大鼠5只，于肾缺血后的再灌注期静脉注射2ml生理盐水。2h后处死动物，收集血液和肾脏标本，行血肌酐（Cr）、尿素氮（BUN）、肾组织超氧化物歧化酶（SOD）和脂质过氧化产物丙二醛（MDA）含量测定，并进行组织病理和超微病理检查。结果实验组大鼠血Cr和BUN水平明显低于对照组（P〈0.05），肾组织中SOD活性较对照组明显升高（P〈0．01），肾组织脂质过氧化产物MDA的含量较对照组明显降低（P〈0．01）。病理学检测表明实验组大鼠肾小管周围毛细血管内未见淤血，肾小管上皮细胞变性及线粒体的损伤减轻。结论EGCG对大鼠肾脏缺血再灌注损伤具有保护作用。     

Sex differences in plasma cocaine levels and subjective effects after acute cocaine administration in human volunteers

Gender differences after acute cocaine administration have received little attention in spite of the fact that males and females respond differently to many drugs. Seven male and seven female occasional cocaine users received both an intranasal dose of cocaine hydrochloride (0.9 mg/kg) and placebo powder in a randomized order and reported subjective effects via an instrumental joystick device and various questionnaires. Blood samples were withdrawn at 5-min intervals to assess pharmacokinetic differences. Male subjects achieved the highest peak plasma cocaine levels (144.4 ± 17.5 ng/ml), detected cocaine effects significantly faster than females and also experienced a greater number of episodes of intense good and bad effects. Women studied during the follicular phase of their menstrual cycle had peak plasma cocaine levels of 73.2 ± 9.9 ng/ml, which was significantly higher than when they were studied during their luteal phase (54.7 ± 8.7 ng/ml), but there were no differences in their subjective reports of cocaine effects. In spite of the different cocaine blood levels and subjective effects, peak heart rate increases did not differ between males and females suggesting that women may be more sensitive than males to the cardiovascular effects of cocaine. These data suggest that there are significant gender and menstrual cycle differences in the response to acute intranasal cocaine administration and these differences may have implications for the differential abuse of this drug.This paper is dedicated to Xavier Lamas, MD, PhD, who lost his life while ascending Mt. Everest, August 1995     

Age-Specific Effects of Baclofen on Pentylenetetrazol-Induced Seizures in Developing Rats

Summary: Purpose : To determine whether seizures have age-specific features, we studied the role of γ-aminobutyric acid, (GABAB) transmission in rats of various ages (9, 15, 30, and 60 postnatal days). Methods: We used a GABA, receptor agonist baclofen (2 or 5 mg/kg intraperitoneally, i.p.) and a GABA_B receptor antagonist CGP 35348 (100 or 600 mg/kg i.p.) in the pentylenetetrazol (PTZ)-induced model of clonic and tonic-clonic seizures (100 mg/kg subcutaneously, s.c.).
Results : Whereas baclofen was anticonvulsant and CGP 35348 proconvulsant in most animals, there were distinct age-related differences in the effectiveness of these drugs and the antagonist had some anticonvulsant activity in adults. Furthermore, the two drugs acting at GABA_B receptors had a different profile of action in clonic seizures as compared with tonic-clonic seizures.
Conclusions : The differences in the age-specific action of the GABA_B agonist and antagonist suggest that different GABA_B receptor subsets may mediate the drug effects. The results indicate that putative antiepileptic drugs (AEDs) must be tested during development because it may not be possible to extrapolate age-specific anticonvulsant effects from studies in adult animals.     

Substitution of the 5-HT1 agonist trifluoromethylphenylpiperazine (TFMPP) for the discriminative stimulus effects of ethanol: effect of training dose

The role of the ethanol training dose on the ability of the selective 5-HT¹ agonist TFMPP (m-trifluoromethylphenylpiperazine) to produce ethanol-like discriminative stimulus effects was evaluated in three groups of rats trained to discriminate 1.0 g/kg (n=5), 1.5 g/kg (n=6) or 2.0 g/kg (n=7) ethanol (IG) from water using a two-lever procedure with food reinforcement available under a fixed ratio 20 (FR 20) schedule. Ethanol generalization gradients were comparable in the three groups, indicating few potency differences in the ethanol stimulus across training dose. However, the ability of TFMPP (0.1–1.7 mg/kg; IP) to substitute for ethanol was dependent on the training dose. TFMPP resulted in partial substitution in the 1.0 g/kg group, complete substitution for 1.5 g/kg group and no substitution in the 2.0 g/kg ethanol training group. The results indicate a serotonergic component to the discriminative stimulus effects of an intermediate dose of ethanol that is not prominent as the dose of ethanol is raised. These data add further support for the hypothesis that ethanol produces a mixed discriminative cue, the components of which are not uniformly amplified when the dose of ethanol is increased.     

男性胆囊结石患者血清性激素和前列腺素改变的探讨

借助RIA,对28例胆囊结石男性(平均57.5岁)及26名健康中、老年男性(平均63.3岁)进行了血清雌二醇(E_2)、孕酮、睾酮和前列腺素类(PGs)检测,以探索胆石形成机理。结果,1)在胆石男病人中.平均E_2和平均孕酮水平均高,他们的平均睾酮则低下,与健康对照男性相应诸值比较,差异非常显著或显著(P<0.001,0.05,0.05);2)至于平均PGs,胆石男性组者与健康对照男性相比,前者也相当高(23.01pg/ml对16.31pg/ml),只是两组间差异尚无统计学意义。作者等初步设想,胆石男性小,如同胆石女性那般,本症也可能是某种垂体性腺激素分泌紊乱性疾病。     

“美容牌”染发剂对雄性小鼠生殖细胞非程序DNA合成的诱导

本文应用雄性小鼠生殖细胞非程序DNA合成(UDS)检测方法研究了“美容牌”染发剂对雄性生殖细胞DNA的损伤作用。发现该染发剂诱发的UDS与药物剂量呈线性正相关。提示此类染发剂对雄性生殖细胞DNA有损伤作用。其遗传毒理效应应引起注意。     

Behavioural specificity of 8-OH-DPAT-induced feeding

8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) has been reported to increase food intake. This effect was confirmed in rats consuming plain or sweetened wet mash. However, the consumption of a 35% sucrose solution or of a range of other flavoured liquids was enhanced marginally if at all by a single low dose of 8-OH-DPAT, and the drug actually decreased the consumption of a high protein liquid diet. 8-OH-DPAT did, however, increase gnawing on a wooden block. These results suggest that 8-OH-DPAT-induced hyperphagia may to some extent be secondary to the elicitation of chewing behaviour. 8-OH-DPAT also caused certain other behavioural changes, including a suppression of grooming.     

The role of dopamine in the facilitatory effect of angiotensin II on impaired learning in rats chronically treated with ethanol

Rats with impaired active avoidance induced by chronic (9 weeks) administration of ethanol were studied. Angiotensin II (ANG II) administered (ICV, 2.0 g) 12 h after the withdrawal of the alcohol not only neutralized the toxic effect of ethanol but also improved learning. When administered on the 5th day after ethanol withdrawal, the effect of ANG II was weaker. Tests of stereotypy and catalepsy were used to study the possible role of the dopaminergic system in this action of ANG II. It was shown that both chronic alcohol treatment and ANG II alone increased apomorphine (1 mg/kg) and amphetamine (7.5 mg/kg) stereotypy but the effects of ANG II were greater. ANG II did not change the stereotypy induced by amphetamine but increased the stereotypy induced by apomorphine in the group of animals chronically treated with alcohol. Haloperidol — induced catalepsy was reduced in these rats. ANG II alone intensified catalepsy and eliminated the effect of ethanol. Both ANG II and alcohol increased striatal dopamine (DA) concentration. This effect of ANG II was significantly greater in the animals chronically treated with alcohol. The above changes were not observed after the DA level had been reduced by alpha-methyl-p-tyrosine (250 mg/kg), nor were changes observed in the striatal DOPAC. The results suggest involvement of the central dopaminergic system in the effect of ANG II on the ethanol — induced impairment of acquisition of active avoidance but, however, the results of the biochemical determinations of DA turnover do not provide an explanation of these changes.