Attenuation by antidepressant drugs of alcohol intake in rats

Ethanol preferring rats were selected and showed a constant voluntary intake of a 12% ethanol solution during 14 days (about 5 g/kg body weight daily). These alcohol preferring rats were daily IP injected during two weeks with different antidepressant drugs, according to their specificity of action: nomifensine (5 and 10 mg/kg) and maprotiline (2.5 and 5 mg/kg) (dopamine uptake inhibitors), desipramine and metapramine (5 and 10 mg/kg) (noradrenaline uptake inhibitors) clomipramine and doxepine (5 and 10 mg/kg) (serotonin uptake inhibitors). Only desipramine, 5 and 10 mg/kg, metapramine, 10 mg/kg, clomipramine, 5 and 10 mg/kg and doxepine, 10 mg/kg, were able to reduce significantly the ethanol intake. These drugs specifically inhibit noradrenaline or serotonin uptake. These data lead us to think that norepinephrine and/or serotonin, but not dopamine, are involved in the voluntary intake of alcohol.     

A new orally active male antifertility agent

CL 88,236 (1-1-amino-3-chloro-2-propanol HC1) was tested orally for antifertility in male rats, mice and hamsters. It was given orally in propylene glycol either daily for 14 days with mating on Days 7-14, (or for 7 days with mating on Days 2, 4, and 6, or for 7 days every other week for 3 weeks in withdrawal tests. In male rats, 5 mg per kg for 14 days reduced number of pregnant females 50%, and at 10-80 mg per kg males were completely sterile. Libido, coitus, and ejaculation were normal, but fragmented sperm, spermatogenic arrest, and granuloma-like epididymal lesions appeared at 40 and 80 mg per kg. Serial matings showed that sterility developed within 6 days and lasted for 1 week after withdrawal. Sterility was maintained by treating rats with CL 88,236 on alternating weeks. Male mice and hamsters were sterilized by 300 mg per kg per day for 14 days, without toxicity. Sterility was apparently mediated by affecting epididymal and vas sperm stores.     

Striatal dopamine does not appear involved in the voluntary intake of ethanol by rats

Ethanol preferring and non preferring rats were selected. Ethanol preferring rats showed a constant voluntary intake of a 12% ethanol solution during 14 days (about 5 g/kg body weight daily) while the non preferring rats drank less than 1 g/kg body weight daily. Preferring rats were daily IP injected with 5 or 10 mg/kg of nomifensine, an inhibitor of dopamine uptake. Their intake of ethanol solution remained constant during the 14 days of treatment. Dopamine uptake into striatal synaptosomes was identical in ethanol preferring and non preferring rats. These data, as others, led us to suppose that striatal dopamine is not involved in the voluntary intake of ethanol by rats.     

Pregnancy interceptive activity of the roots of Calotropis gigantea Linn. in rats

OBJECTIVE: We conducted this study to evaluate the pregnancy interceptive activity of the roots of Calotropis gigantea Linn. in colony-bred adult Sprague-Dawley rats when administered during the preimplantation and/or peri-implantation periods. METHODS: The ethanolic extract of the roots of C. gigantea Linn. and its hexane, chloroform, n-butanol-soluble and n-butanol-insoluble fractions were administered to rats on Day 1, Days 1-5, Days 1-7 or Days 5-7 postcoitum. Rats from the control group received an equal volume of the vehicle (Tween 80 in glass distilled water) only. At autopsy on Day 10 postcoitum, the final body weight and number as well as status of the corpora lutea and implantations in each animal were recorded. For estrogen agonistic and antagonistic activities, 21-day-old immature rats ovariectomized 7 days earlier were treated orally with the test agent or the vehicle for 3 days. In the case of estrogen antagonistic activity, the rats also received 0.05 mg/kg of 17alpha-ethinyl estradiol for 3 days. At autopsy 24 h after the last treatment, uterine fresh weight was taken and premature opening of the vagina as well as the extent of vaginal cornification, if any, were recorded. RESULTS: The ethanolic extract of the roots of C. gigantea Linn. exhibited 100% pregnancy interceptive activity in rats when administered as a single oral dose of 100 mg/kg on Day 1 postcoitum. The extract also exhibited 100% efficacy at the dose of 12.5 mg/kg when administered in the Days 1-5 and 1-7 postcoitum schedules. When administered during the peri-cum-early postimplantation period (i.e., Days 5-7 postcoitum at 250 mg/kg), most of the implantations showed signs of resorption. On fractionation, the chloroform fraction showed 100% activity at 100 mg/kg in the single-day (Day 1 postcoitum) schedule, whereas the hexane, n-butanol-soluble and n-butanol-insoluble fractions were found to be inactive at this dose. At autopsy on Day 10 postcoitum, 7-25% loss in body weight was recorded at the minimum effective contraceptive dose (MED) in rats treated with the ethanolic extract as well as its chloroform-soluble fraction on Days 1-7, 1-5 and 1 postcoitum, in comparison with the 6-7% increase in body weight observed in vehicle control rats. There was however no mortality in any of the treatment groups. The active ethanolic extract and its chloroform fraction were devoid of any estrogen agonistic or antagonistic activity at their respective MEDs in the ovariectomized immature rat bioassay. Efforts are being made to isolate the active principles devoid of effect on body weight. CONCLUSIONS: The findings suggest the potential for developing products of this plant as contraceptives for human use and welfare. In addition, characterization of the agents responsible for body weight decrease and evaluation of their mechanism of action and safety profile, with or without contraceptive efficacy, might have added advantage for the management of obesity.     

Protective effect of hesperetin against haloperidol-induced orofacial dyskinesia and catalepsy in rats

Objectives: The present study was designed to evaluate the effect of hesperetin on haloperidol-induced orofacial dyskinesia and catalepsy in Wistar male albino rats.

Methods: Haloperidol (1?mg/kg, ip) was administered for 21 successive days to induce orofacial dyskinesia and catalepsy. Hesperetin (50 and 100?mg/kg, po) was administered 10?min prior to the injection of haloperidol for 21 successive days. Vacuous chewing movements (VCMs), tongue protrusions, catalepsy, and locomotor activity scores were recorded on 7th, 14th, and 22nd day of drug treatment. After behavioral testing, animals were sacrificed and various biochemical parameters such as brain levels of dopamine, serotonin, malondialdehyde, and reduced glutathione (GSH); and superoxide dismutase (SOD) and catalase activities were estimated.

Results: Chronic administration of haloperidol significantly increased VCMs, tongue protrusions, and catalepsy in rats. It also produced hypolocomotion in rats. Hesperetin significantly inhibited haloperidol-induced VCMs, tongue protrusions, and catalepsy. Haloperidol significantly increased brain levels of malondialdehyde, decreased brain GSH, SOD, and catalase activities; and also decreased brain dopamine and serotonin levels. Hesperetin significantly reversed haloperidol-induced increase in brain oxidative stress and decrease in brain dopamine and serotonin levels.

Discussion: Hesperetin significantly ameliorated haloperidol-induced orofacial dyskinesia and catalepsy possibly through alleviation of oxidative stress and increase in brain dopamine and serotonin levels. Thus, hesperetin may be explored further as a possible therapeutic agent for clinical management of neuroleptic drug-induced tardive dyskinesia.     

Effects of acute and short-term administration of tryptophan plus ethanol on noradrenaline and serotonin metabolites in the locus coeruleus.

The effects of acute and short-term administration of tryptophan or tryptophan plus ethanol on serotonin [5-hydroxytryptamine (5-HT)] and two of its metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and 5-hydroxytryptophol (5-HTPL), in the locus coeruleus were investigated in rats by using the microdialysis method. In addition, the acute effects of these drugs on noradrenaline and its metabolite 4-hydroxy-3-methoxymandelic acid (HMMA) were addressed. A single co-administration of tryptophan (50 mg/kg, i.p.) and ethanol (1.25 g/kg, i.p.) did not change the concentrations of either noradrenaline or its metabolite in the locus coeruleus. In contrast, administration of tryptophan (50 mg/kg, i.p.) for three consecutive days caused an increase in the concentration of 5-HIAA, but not that of 5-HT, in the locus coeruleus. Combined administration of tryptophan plus ethanol for 3 days resulted in marked increases in 5-HIAA concentrations in the locus coeruleus, but not in 5-HTPL concentrations. However, administration of ethanol (1.25 g/kg) for 3 days had no effect on the concentrations of 5-HT and its metabolites. The increased 5-HIAA concentration that resulted with combined tryptophan plus ethanol administration was remarkably suppressed by disulfiram. Moreover, in comparison with tryptophan-treated rats, the behavioral sign of teeth-chattering was significantly detected in tryptophan plus ethanol-treated rats, but the enhancement of behavioral signs with combined treatment was markedly suppressed by disulfiram. Results of the current study seem to indicate that the stimulation of 5-HT metabolism in locus coeruleus serotonergic neurons by tryptophan was strengthened by the simultaneous administration of ethanol in short-term experiments, and that the increased 5-HIAA concentrations in the locus coeruleus are responsible for behavioral activation.     

多巴胺受体激动剂对丙烯酰胺诱导大鼠神经损伤的影响

目的 研究丙烯酰胺对大鼠中枢神经系统神经递质多巴胺含量的影响以及多巴胺受体激动剂对丙烯酰胺引起的神经损伤的影响,探讨丙烯酰胺的神经损伤机制以及确定多巴胺受体激动剂对丙烯酰胺引起的神经损伤是否具有保护作用.方法 SD大鼠染毒组腹腔注射丙烯酰胺4周,每周5次(30 mg/kg);溴隐亭给药组在腹腔注射丙烯酰胺的同时灌胃给予多巴胺受体激动剂溴隐亭(低剂量组按1.25 mg/kg给药,高剂量组按2.5 mg/kg给药);正常对照组腹腔注射等量生理盐水.每周给药第6天和第7天对大鼠进行感觉神经功能测定以及自主性行为观察.给药结束后,测定大鼠中枢神经系统多巴胺、肌酸激酶(CK)以及Na -K -ATP酶的含量.结果 染毒组大鼠体重呈下降趋势,与其他3组大鼠体重均存在明显差异,染毒组热反应灵敏度也较差,给药组无论低剂量或高剂量组,热反应灵敏度均比染毒组有所改善.此外,染毒组CK、Na -K -ATP酶以及多巴胺的含量均比正常对照组明显减少,给药组各指标也比阳性对照组有所升高.结论 多巴胺受体激动剂溴隐亭对丙烯酰胺诱导的大鼠神经损伤有一定的保护作用.     

Role of corticosterone in cleft palate formation in methylmercuric chloride-treated mice

The effect of simultaneous administration of sodium selenite and methylmercuric chloride on plasma corticosterone, and the effect of adrenalectomy and methylmercuric chloride treatment on the incidence of fetal cleft palate in mice were examined. After 6 consecutive days of treatment, methylmercury (as methylmercuric chloride) at 5 mg/kg per day increased plasma corticosterone to approximately twice the concentration observed in the controls. When administered together, selenium (as sodium selenite) at 125–135 mg/kg per day did not affect the increase of plasma corticosterone induced by methylmercuric chloride. Selenite by itself (125–135 mg selenium/kg per day) resulted in an increase of approximately 50% over the controls. Sham operation or adrenalectomy of mice on Day 7 of pregnancy did not result in a significant incidence of cleft palate in the fetuses. However, the administration of methylmercury (5 mg/kg per day) on Days 11, 12, and 13 of gestation to the operated mothers resulted in cleft palate in approximately 30% of the fetuses, regardless of the type of operation. The significance of these findings is discussed.     

Effect of cadmium on hepatic metallothionein level in early development of the rat

The induction of hepatic metallothionein (MT) was investigated 24 hr after an intraperitoneal injection of 0.75 mg/kg Cd as CdCl₂ · H₂O in rats of 7, 14, 21, and 90 days. Metallothionein in liver cytosolic fractions collected on Sephadex G-75 was characterized in terms of sulfhydryl, total protein, Cd, and Zn contents. Most of the cytosolic Cd was associated with MT and the concentration of Cd was equal in the different age groups. The higher contents of sulfhydryl, protein, and Zn both in control as well as in Cd-injected rats of 7 and 14 days than in those of 21 and 90 days indicate the presence of more native Zn-thionein in immature pups. However, the increase in sulfhydryl and protein contents showed more prominent induction of MT in Cd-exposed animals of 21 and 90 days than in those of 7 and 14 days. The concentration of Cd was highest in liver followed by the other tissues. While hepatic accumulation of Cd was similar in all age groups, the renal accumulation increased significantly with age. The intestine and spleen of immature pups concentrated more Cd than those of mature animals. The accumulation of the metal did not differ significantly in heart and brain of the animals among the four groups.     

菌核净内分泌干扰作用研究

目的研究菌核净内分泌干扰作用(雌激素和抗雄激素活性作用)。方法通过不同实验终点探讨菌核净雌激素样作用:(1)每隔5天腹腔注射给予鲫鱼不同浓度菌核净(0、50、100和200mg/kg)诱导卵黄蛋白原(VTG)的产生,2周后收集雄性鲫鱼血浆和肝脏进行VTG检测;(2)人乳腺癌细胞(MCF-7细胞)中加入不同浓度的菌核净(10-10～10-4mol/L),作用3天后观察菌核净诱导细胞增殖情况;(3)雌性小鼠去势后给予不同浓度菌核净(0、125、250和500mg/kg),计算子宫脏器系数。Hershberger试验研究菌核净抗雄激素样作用:雄性大鼠去势后给予不同剂量的菌核净(0、30、60和120mg/kg),同时皮下注射雄性激素丙酮酸睾酮(TP),计算雄激素依赖组织的脏器系数。结果100mg/kg和200mg/kg菌核净能诱导雄性鲫鱼血VTG产生,200mg/kg菌核净能刺激雄性鲫鱼肝脏产生VTG,与阴性对照组相比,VTG含量差异均具有显著性(P<0.05);各剂量组菌核净对雄性鲫鱼血钙离子、血和肝总蛋白含量均无影响,但阳性对照E2能增高血钙离子水平;10-8、10-7和10-6mol/L菌核净能诱导MCF-7细胞增殖,与对照组相比,差异具有显著性(P<0.05);菌核净3个剂量组均能增加去势小鼠子宫脏器系数,其中250mg/kg组与阴性对照组比较差异具有显著性(P<0.05);60mg/kg和120mg/kg菌核净均能降低前列腺加精囊腺、肛提肌、球海绵体肌的脏器系数,与模型对照组比较,差异具有显著性(P<0.05)。结论菌核净具有雌激素和抗雄激素双重内分泌干扰作用。     

The effect of prenatal methylmercury administration on postnatal renal functional development

In utero exposure of rats to methylmercury has been reported to produce degenerative and hyperplastic changes in renal proximal and distal tubules, although no assessment of postnatal renal functional capacity was made. CH₃HgCl was administered ip to Sprague-Dawley rats on Day 8 of gestation at 4 or 6 mg Hg/kg or on Days 8, 10, and 12 at 4 mg Hg/kg (3 × 4 mg Hg/kg). These doses produced no overt toxicological effects nor had any effect on litter size, body weight, or kidney weight to body weight ratios. The concentration of mercury in kidneys, liver, and brain at 1 and 7 days postpartum was dose-related but was not detectable at 42 days. In vitro renal function was assessed in renal cortical slices from rats at 1, 7, and 42 days postpartum by determining the ability to accumulate organic ions and to generate glucose. Additionally, parameters of in vivo renal function were determined in normopenic, hydropenic (5 pressor units/kg ADH, sc, 18 hr water deprived), and in volume-loaded male rats at 42 days postpartum. At 42 days postpartum in the 3 × 4 mg Hg/kg treatment group, p-aminohippurate accumulation was depressed slightly as was the ability to eliminate Na⁺ and water in volume-loaded rats. These data suggest that postnatal renal physiological sequelae to prenatal administration of methylmercury may be less than predicted from histological studies.     

Contraceptive and hormonal properties of the stem bark of Dysoxylum binectariferum in rat and docking analysis of rohitukine, the alkaloid isolated from active chloroform soluble fraction

BACKGROUND: This study was aimed to investigate the pregnancy interceptive activity of the stem bark of Dysoxylum binectariferum Hook. f. administered during the pre- and peri-implantation periods and immediately after implantation by oral route in adult female Sprague-Dawley rats. STUDY DESIGN: Ethanolic extract and its fractions were administered to female rats on Days 1-10, Days 1-7, Days 1-5 or Day 1 postcoitum by oral route. At autopsy on Day 12, the number and status of corpora lutea and implantations were recorded. For estrogenic activity, ovariectomized immature rats received the test extract or the vehicle once daily for 3 days and at autopsy on Day 4, uterine weight and status of vaginal opening and extent of vaginal cornification were recorded. For antiestrogenic activity, the extract was administered along with ethinyl estradiol. Docking analysis of rohitukine, the alkaloid isolated from active chloroform soluble fraction, to estrogen receptor (ERalpha) was conducted using AutoDock 3.0.5 on a Linux workstation. RESULTS: The ethanolic extract intercepted pregnancy in rats at a daily dose of 500 mg/kg on Days 1-7 postcoitum. On fractionation, the activity was localized in the chloroform fraction, which inhibited pregnancy in all females at the 35-mg/kg dose on Days 1-7, at the 50-mg/kg dose on Days 1-5 or at the single 300-mg/kg dose on Day 1 postcoitum. Chromatography of this fraction yielded an alkaloid, rohitukine, which prevented pregnancy at the 10-mg/kg dose administered on Days 1-7 but was partially (45%) effective at this dose when administered during the entire preimplantation period and ineffective even at 10 times this dose when administered only on Day 1 postcoitum, except that there was a significant reduction in implantation number in pregnant females. While the active chloroform soluble fraction was devoid of any estrogen agonistic or antagonistic properties, a mild uterotropic effect without induction of premature opening of vagina or cornification of vaginal epithelium was observed in rohitukine at the 10-mg/kg dose. Rohitukine, with an almost similar molecular size (mol. wt. 305) as 17beta-estradiol, fits ideally into the hydrophobic pocket of ER. While it does not appear to simultaneously interact with GLU353, ARG394 and HIS524 as estradiol to elicit frank estrogenic response, different conformations of the ligand or its metabolite(s) might acquire geometry with phenolic groups at C-3', C-5 and C-7 positions disposed in a fashion to interact with active site(s) of ER, which might be responsible for its contraceptive and/or weak uterotropic effects. The absence of a basic side chain directed toward the antiestrogen binding site (ASP351) on the receptor appears to be responsible for the lack of any estrogen antagonistic activity. CONCLUSIONS: Findings demonstrate the antifertility activity of the ethanolic extract of D. binectariferum, its chloroform soluble fraction and rohitukine. Efforts are being made to enhance the anti-implantation activity of rohitukine by structural modifications.     

抽动障碍动物模型的行为学研究

目的 观察亚氨基二丙腈(iminodipropionitrile,IDPN)和2,5-二甲氧-4-碘苯-2-氨基丙烷(±-1-2,5-dimethoxy-4-iodophenyl-2-aminopropane,DOI)诱导的抽动障碍(tic disorder,TD)动物模型的运动抽动和刻板行为表现,为选择可以更好地模拟TD特征性行为的造模方法提供依据。方法 SD大鼠30只随机分3组,每组10只。IDPN组大鼠给予IDPN 150 mg/kg腹腔注射,连续7 d,DOI组大鼠给予DOI 1 mg/kg腹腔注射,连续15 d,正常组给予生理盐水腹腔注射,连续7 d,给药体积均为1 mL/100 g。造模结束后记录各组大鼠在造模结束第1至第7天、第14天和第28天的运动行为评分、刻板行为评分和分类刻板行为评分。结果 IDPN组和DOI组大鼠在第1至第4天的运动评分、刻板行为评分,除理毛、舔咬笼子以外的分类刻板行为评分均高于正常组,且IDPN组大鼠在第5、6、7、14、21、28天的运动评分和第5、7、14、21、28天的刻板行为评分均高于正常组和DOI组,差异均有统计学意义(P＜0.05)。IDPN组大鼠的吃木屑、旋转、摆头、舞蹈样运动等分类刻板运动评分均高于DOI组,DOI组大鼠口爪运动、自咬等分类刻板运动评分均高于IDPN组,差异均有统计学意义(P＜0.05)。结论 IDPN模型与DOI模型均可以模拟抽动患者的兴奋性增高,活动增多和抽动等症状,表观效度较好。与DOI模型相比较,IDPN模型具有建模时间短,模型维持时间长久,且花费较少等优势。     

Changes in food intake and stomach contents of tumor-bearing rats after treatment with dopamine antagonists

The appetite-stimulating (orexigenic) potential of the peripheral dopamine (DA) receptor antagonist domperidone was compared with that of the central DA antagonist pimozide in anorexic, tumor-bearing rats. DA antagonists were administered via the intraperitoneal route on Days 7-15 after the subcutaneous implantation of the Walker 256 carcinosarcoma. The doses of domperidone injected were 0.05 and 0.1 mg/kg once daily and 0.1 mg/kg twice daily. The dose of pimozide given was 0.1 mg/kg daily. While all doses of DA antagonists caused an initial drop in body weight and food intake, the body weight of pimozide-injected animals was not reduced significantly (in the early stages of drug treatment) as it was with the various doses of domperidone. There was significantly more food in the stomachs of domperidone- and pimozide-treated animals compared with those of the vehicle-treated, tumor-bearing animals at the time of sacrifice. These results indicate that short- and long-term satiety factors, in addition to gastric motility, should be considered when assessing the orexigenic potential of various drugs.     

Comparative effects of carbohydrate restriction vs starvation on biochemical parameters related to neurotransmitters in rat

Adult rats were submitted to a 4-day starvation period or maintained on a 50% carbohydrate-restricted diet for 8 consecutive days to obtain a body weight loss of 20-30%. Serum dopamine-beta-hydroxylase (DBH) activity and amino acids content were measured as well as brain tryptophan and tyrosine levels. Moreover, brain serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline (NA), and dopamine (DA) contents were assayed in five brain areas. In 4-day starved and 8-day carbohydrate-restricted rats, the serum tyrosine and total tryptophan contents as well as tyrosine to the sum of six neutral amino acids ratios were lowered. Moreover, in these groups, free tryptophan to the sum of six neutral amino acids ratio remained normal and serum DBH activity increased. In the brain, to a decreased tyrosine content observed in 4-day starved and 8-day carbohydrate-restricted rats corresponded a high DA to NA ratio in the hypothalamus, thalamus, and raphe nuclei, thus suggesting a low DA utilization whereas a low DA to NA ratio was found in the neostriatum. On the other hand, brain tryptophan content was decreased in 4-day starved rats and increased in 8-day carbohydrate-restricted rats. In the former group, a high 5-HT to 5-HIAA ratio characteristic of a low 5-HT utilization was found in the hypothalamus and neostriatum whereas in the latter group a significant decrease in this ratio was only observed in the thalamus. These results suggest that the biochemical response to starvation vs carbohydrate restriction can be differentiated on neurochemical and neuroanatomical bases.     

丙烯酰胺对大鼠神经行为和黑质纹状体多巴胺及其代谢产物含量的影响

目的初步探讨丙烯酰胺(ACR)对大鼠神经行为的影响,并通过测定黑质纹状体多巴胺(DA)及其代谢产物二羟苯乙酸(DOPAC)、高香草酸(HVA)含量阐明其可能机制。方法将健康成年雄性SD大鼠随机分成对照组和ACR组,每组7只。ACR组以40mg/kg的ACR灌胃染毒,对照组灌胃等容量的生理盐水,连续12天。第0、3、6、9和12天分别评定步态分值、后肢撑力及甩尾时间。末次给药后24小时,断头处死,于冰盘上迅速分离纹状体,HPLC荧光检测法检测DA及其代谢产物的含量。结果与对照组相比,ACR组大鼠的步态评分、后肢撑力指数显著性升高(P<0.01),甩尾时间显著降低(P<0.01)。纹状体内DA含量与对照组相比,约降低了65.64%,差异有显著性(P<0.01)。结论 ACR能引起大鼠神经行为功能的改变,同时能降低纹状体内DA含量,黑质纹状体DA系统可能参与了ACR的神经毒性作用。     

Melatonin reduces oxidative stress induced by chronic exposure of microwave radiation from mobile phones in rat brain

PURPOSE: The aim of the study was to evaluate the intensity of oxidative stress in the brain of animals chronically exposed to mobile phones and potential protective effects of melatonin in reducing oxidative stress and brain injury. MATERIALS AND METHODS: Experiments were performed on Wistar rats exposed to microwave radiation during 20, 40 and 60 days. Four groups were formed: I group (control)- animals treated by saline, intraperitoneally (i.p.) applied daily during follow up, II group (Mel)- rats treated daily with melatonin (2 mg kg(-1) body weight i.p.), III group (MWs)- microwave exposed rats, IV group (MWs + Mel)- MWs exposed rats treated with melatonin (2 mg kg(-1) body weight i.p.). The microwave radiation was produced by a mobile test phone (SAR = 0.043-0.135 W/kg). RESULTS: A significant increase in the brain tissue malondialdehyde (MDA) and carbonyl group concentration was registered during exposure. Decreased activity of catalase (CAT) and increased activity of xanthine oxidase (XO) remained after 40 and 60 days of exposure to mobile phones. Melatonin treatment significantly prevented the increase in the MDA content and XO activity in the brain tissue after 40 days of exposure while it was unable to prevent the decrease of CAT activity and increase of carbonyl group contents. CONCLUSION: We demonstrated two important findings; that mobile phones caused oxidative damage biochemically by increasing the levels of MDA, carbonyl groups, XO activity and decreasing CAT activity; and that treatment with the melatonin significantly prevented oxidative damage in the brain.     

Effects of 5-HT(3) receptor antagonists on daily alcohol intake under acquisition, maintenance, and relapse conditions in alcohol-preferring (P) rats.

Previous research indicated that 5-HT(3) antagonists can reduce ethanol drinking in rats, but drinking conditions and other environmental manipulations influenced the efficacy of these antagonists. The current experiments were conducted to examine the effects of the 5-HT(3) antagonists MDL 72222 (MDL) or ICS 205-930 (ICS) on 24-h ethanol (10% v/v) consumption during acquisition, maintenance, and following a period of deprivation in selectively bred high alcohol-preferring (P) male rats. In an analysis of the acquisition of ethanol consumption, daily injections of MDL (1 mg/kg; s.c.) or ICS (1 or 5 mg/kg) were administered to separate groups of P rats during the initial 10 days of ethanol exposure. To examine the maintenance of ethanol drinking, these same groups of rats were allowed access to ethanol for 21 days with no pharmacological manipulations, and were then administered either saline or the 5-HT(3) antagonist. To examine the effects of a 5-HT(3) antagonist on relapse of ethanol drinking, another group of P rats was allowed access to ethanol for 6 weeks and was then deprived of ethanol for 3 weeks. Prior to ethanol reinstatement, rats were treated chronically (seven daily injections) or acutely with MDL (1 mg/kg), saline, or received no injections. MDL (1 mg/kg) and ICS (1 or 5 mg/kg) reduced ethanol intake during acquisition (60-80%) and during maintenance drinking (35-70%) in P rats pretreated with saline during acquisition. However, in rats pretreated with MDL or ICS during acquisition, there was a significant reduction in the effectiveness of either MDL or ICS to reduce ongoing ethanol drinking. Neither acute nor chronic treatment with 1 mg/kg MDL altered the 80% increase in ethanol consumption observed on the first day of reinstatement following a 3-week deprivation period. However, in a follow-up study, acute treatment with MDL (3 mg/kg) or ICS (5 mg/kg) did prevent the 80% increase in ethanol consumption observed on the first day of reinstatement. Overall, the results suggest that 5-HT(3) receptors are involved in the acquisition and maintenance of 24-h ethanol drinking, and that neuroadaptations may occur as a result of chronic treatment with 5-HT(3) antagonists, or during prolonged alcohol deprivation, which alter the involvement of these receptors in regulating alcohol drinking in the P rat.     

不同暴露时间TiO2纳米粒子对雌性小鼠脑单胺类神经递质的影响

目的探讨小鼠鼻腔滴注二氧化钛（TiO2）纳米粒子对脑中单胺类神经递质的影响。方法以50mg／kg的剂量给CD雌性小鼠隔天鼻腔滴注不同粒径大小的TiO：（25、80和155nm）水悬浮液（浓度为10^5mg／L）,同时设定对照组。分别在暴露2、10、20和30d后用电感耦合等离子体质谱仪分析小鼠脑组织中钛元素的含量,采用反相高效液相色谱-电化学检测法测定暴露20和30d后小鼠脑中单胺类神经递质的含量。结果在暴露10d时,小鼠脑中钛的含量上升较快,25nm组小鼠脑中钛的含量即达到（1059．3±293.5）ng／g;在暴露20d之后,脑中钛的含量有一定降低,仍维持在较高水平,25nm组中钛的含量下降为（654.7±269．2）ng／g。暴露30d时钛含量没有明显改变。由于吸入的TiO2粒子在小鼠脑中的蓄积,导致80nm和155nm组中小鼠脑中去甲肾上腺素（NE）和5-羟色胺（5-HT）含量在暴露20d时明显升高,而多巴胺（DA）、3、4-双羟苯乙酸（DOPAC）、高香草酸（HVA）和5-羟吲哚乙酸（5-HIAA）的含量有一定下降。结论吸入的TiO2颗粒可以经鼻黏膜吸收入脑并能蓄积于小鼠的脑组织中,影响脑中单胺类神经递质的代谢。     

Prototype for a new class of antifertility agents, 3,5-Bis (dimethylahino)-1,2,4,-dithiazolium chloride

3,5-Bis(dimethylarmino)-1,2,4-dithiazolium chloride [ORF 5513] is considered to be a prototype for a new class of female antifertility agents. When orally administered to rats at dose levels between 0.01 and 0.1 mg/kg/day for 3 days prior to expected ovulation, treatment resulted in a dose-dependent inhibition of ovulation. However, when the compound was administered to animals for 2 days prior to ovulation, ORF 5513 had little or no effect on ovulation at doses as high as 10 mg/kg/day. ORF 5513 also interrupted pregnancy at several stages of gestation, including implantation, placentation and late pregnancy. The minimum effective dose (MED) in the rat for inhibiting implantation (Days 1–6) and interrupting pregnancy immediately after implantation (Days 7–10) appears to be ≤ 10 mg/kg. The MED varies between ≤ 5 mg/kg for days 10–13 or 13–16 to ≤ 20 mg/kg for days 16–19 of gestation. Endocrine bioassays and $\text{in vitro}$ studies revealed that ORF 5513 lacks hormonal activity. Histological studies indicated that the corpora lutea in all animals appeared uninvolved. When the treatment was initiated on day 16 of gestation, the earliest detectable cellular changes occurred in the chorionic villi and chorionic fetal vessels which effectively interfere with fetal circulation. Degeneration of the fetus occurred by day 19 of gestation while maternal placental circulation remained intact.