咳尔康口服液对中枢神经系统的一般药理学研究

目的:研究咳尔康口服液一般药理学作用,观察咳尔康口服液对大鼠中枢神经系统的影响。方法:120只SD大鼠随机分成四组,咳尔康口服液低、中、高剂量以及空白对照组,每组30只,咳尔康口服液低、中、高剂量组分别给予相应药物16.65、33.30、66.60 ml.kg-1灌胃,空白对照组给予同等体积生理盐水,以翻正反射消失法记录药物对大鼠戊巴比妥钠睡眠时间的影响;采用高架十字迷宫视频分析系统,观察药物对大鼠翻正反射和自由活动行为的影响。结果:咳尔康口服液对大鼠睡眠时间、自由活动行为和翻正反射的影响与正常对照组比较,差异无显著性(p0.05)。结论:咳尔康口服液对大鼠中枢神经系统无明显影响。     

硝硫氰胺对神经系统的作用

硝硫氰胺(NDIT)ig0.48/(kg.d)×3或ig2.5g/(kg.d)×3能促进阈下催眠剂量的戊巴比妥钠ip25mg/kg引起小鼠睡眠,能提高中枢兴奋药的半数惊厥剂量(TD_(50)),表明NDIT与戊比妥巴钠有协同作用,与中枢兴奋药有拮抗作用。小鼠、猫NDITig后的EEG表现与镇静催眠药相似,引起急性中毒的主要症状为中枢抑制,共济     

司帕沙星对试验动物的一般药理研究

小鼠单次经口灌服司帕沙星4、20和100mg/kg后,动物的活动正常,未出现兴奋的抑制作用;小鼠单次经口灌服司帕沙星4、20和100mg/kg,与戊巴比妥钠镇静催眠无明显协同作用;给猫静脉注射司帕沙星4、16和64mg/kg,对动物呼吸和心血管系统无明显影响。     

大安颗粒对戊巴比妥钠致小鼠睡眠的影响

大安颗粒由白芍等 1 2味中药组方 ,具滋阴血、宁心神等功效 ,在观察其对实验动物镇静作用的基础上 ,考察了对戊巴比妥钠致小鼠睡眠的影响。实验采用大安颗粒的流浸膏 (3 .0 g(生药 )·ml 1) ,系成都中医药大学科技中试中心研制提供。　　健康昆明种雄性小鼠 5 0只 ,按体重随机分为阴性对照组 (灌服蒸馏水 3 0ml·kg 1) ,阳性对照组 (灌服安定 0 .75mg·kg 1) ,高、中、低大安颗粒 (流浸膏 )组分别以 2 0 1 %、1 3 5 %和 67.3 %的浓度灌服 3 0ml·kg 1(相当于临床拟日用量的 3 0、2 0和 1 0倍 ) ,灌服受试物后60’ ,各组各鼠腹腔注射 0 .1 8%…     

注射用清开灵冻干粉的一般药理作用研究

目的:观察注射用清开灵冻干粉对动物中枢神经系统、心血管系统、呼吸系统的影响及对戊巴比妥钠阈下催眠剂量作用的影响。方法:尾静脉注射给予小鼠不同剂量注射用清开灵冻干粉,或同时腹腔给予阈下催眠剂量的戊巴比妥钠,观察小鼠一般行为学指标和自主活动的变化,以及对戊巴比妥钠阈下催眠剂量的影响;给予麻醉犬不同剂量清开灵冻干粉观察该药对血压,心电图以及呼吸指标的影响。结果:注射用清开灵冻干粉大剂量(210.18 mg/kg)对小鼠有中枢神经系统抑制作用(P<0.05),并有延长巴比妥类睡眠时间的作用(P<0.05)。对犬心血管系统及呼吸系统的影响试验结果显示,清开灵冻干粉各剂量(43.92 mg/kg、21.96 mg/kg、10.98 mg/kg)均对麻醉犬心血管系统及呼吸系统均无影响(P>0.05)。结论:注射用清开灵冻干粉有一定程度的中枢神经系统抑制作用。对心血管系统(心率、心率节律、心电图)、呼吸系统(呼吸频率、呼吸深度、呼吸节律)无明显影响。     

淫羊藿和女贞子提取物对骨质疏松症大鼠性激素功能水平的影响

目的:探讨淫羊藿和女贞子提取物对骨质疏松症(OP)大鼠性激素功能水平的影响。方法:50 只3 月龄雄性Wistar 大鼠随机分为正常组、模型组、提取物低剂量组、提取物中剂量组、提取物高剂量组共5 组,每组10 只,除正常组外,其他4 组以维甲酸灌喂15 d 制作OP 模型,造模成功后正常组和模型组灌服生理盐水,提取物低剂量组、中剂量组和高剂量组分别按50 mg/ kg、100 mg/ kg、200 mg/ kg 灌服淫羊藿和女贞子提取物混合物,均持续3 周。测量各组骨密度(BMD),左侧股骨切片采用苏木精和伊红(HE)染色观察股骨病理学改变并测定骨小梁组织形态相关参数,免疫组织化学分析激素受体蛋白表达。结果:正常组股骨全部、股骨上端、股骨下端BMD 显著高于模型组,提取物中剂量组和高剂量组股骨全部、股骨上端、股骨下端BMD 显著高于模型组,提取物低剂量组股骨全部BMD 显著高于模型组,差异均有统计学意义(P<0郾05 或P<0郾01);与模型组比较,提取物各组骨小梁数量有了显著增加,完整性、连续性明显好转,相关参数比较结果显示,正常组Tb.N、Tb.Ar、Tb.Th 显著大于模型组,Tb.Sp 显著小于模型组,提取物中剂量组和高剂量组Tb.N、Tb.Ar、Tb.Th 显著大于模型组,Tb.Sp 显著小于模型组,提取物低剂量组,Tb、Ar、Tb、Th 显著大于模型组,差异均具有统计学意义(P<0.05 或P<0.01);正常组AR、ER蛋白表达量明显高于模型组,而提取物高剂量组AR、ER 蛋白表达量较模型组显著上升,差异有统计学意义(P<0.05 或P<0.01)。结论:淫羊藿和女贞子提取物能够增加维甲酸诱导的OP 大鼠BMD,逆转骨组织病理结构,上调性激素受体蛋白表达,对维甲酸诱导的OP 大鼠具有潜在的保护作用。     

过量饮酒对凋亡相关基因bcl-2、bax在生精细胞表达的影响

目的　研究长期过量饮酒对凋亡相关基因bcl - 2、bax在睾丸及生精细胞中表达的影响。方法　利用人类饮用白酒制备大鼠的酒精毒性模型 ,采用免疫组织化学技术 ,检测酒精对Bcl- 2、Bax蛋白在睾丸及生精细胞表达的影响。结果　高剂量的酒精作用于大鼠 2个生精周期 ,每个生精小管中Bcl- 2蛋白表达的阳性细胞数目在高剂量组为 96± 33.74 ,低剂量组为 15 6 .6± 2 8.5 2 ,均显著低于正常对照组 (2 2 2 .6± 5 6 .86 ) (P <0 .0 1)。每个细胞中Bcl- 2蛋白表达强度 (OD值 )在高剂量组 (0 .14 2± 0 .0 35 )、低剂量组 (0 .15 1± 0 .0 2 6 ) ,都明显低于对照组 (0 .196± 0 .0 32 ) (P <0 .0 1) ;Bax蛋白表达的阳性细胞数在高剂量组为 (4 12 .4± 96 .75 ) ,低剂量组为 (337.5± 94 .39) ,均明显高于对照组 (2 14± 82 .5 7) (P <0 .0 1) ,Bax蛋白的表达强度 (OD值 )在高剂量组 (0 .113± 0 .0 36 )和低剂量组 (0 .0 82± 0 .0 17) ,均明显高于对照组 (0 .0 5± 0 .0 2 4 ) (P <0 .0 1)。结论　长期过量饮酒使睾丸及生精细胞中bcl- 2的表达降低 ,bax的表达增强。     

低剂量棉酚与甾体激素联合用药对大鼠生精细胞凋亡的影响

采用检测细胞凋亡的微核 (MN)、原位末端标记检测 (ISEL)及单细胞凝胶电泳 (SCGE)等方法 ,研究低剂量棉酚与激素组合用药对大鼠生精细胞凋亡的影响 ,分析不同剂量棉酚 (高剂量 10 0mg/(kg·d)、中剂量 6 0mg/(kg·d)及低剂量 12mg/(kg·d) )及维持量棉酚对生精细胞凋亡及DNA的作用。结果表明不同剂量的棉酚G与单剂量激素H(甲基睾丸素 2 0mg/(kg·d)、炔雌醇 10 0 (g/(kg·d) )合并用药 6周后 ,生精细胞的凋亡系数和微核率随棉酚剂量的增大而增加。高和中剂量棉酚组的凋亡系数分别为 3 5 2 0± 0 4 6 5和 2 0 2 0± 0 0 17,显著高于对照组 (0 2 33± 0 0 88)(P <0 0 5 )。微核率在高剂量组为 2 7 6 33± 3 75 5 ,显著高于对照组 (5 6 0 0± 1 137) (P <0 0 5 ) ;而低剂量组 (3 5 6 7±0 86 9)反而显著低于对照组。服低剂量棉酚G +H 6周后继续服单独低剂量棉酚 (12mg/(kg·d) ) 12周 ,单细胞凝胶电泳未见生精细胞出现DNA单链断裂的彗星状细胞核 ,与高、中剂量组较多的出现率形成明显对照。结果提示低剂量棉酚与甾体激素组合用药在睾丸生精过程中互为调节 ,棉酚引起的生精细胞凋亡效应可在甾体激素的调节下降低而起保护作用     

丝瓜络对实验性高血脂大鼠的降血脂效应

目的 :探讨中药丝瓜络 (LuffacylindericaRoam)对实验性高血脂大鼠的降血脂效果 ,以及对实验大鼠体重的影响。方法 :雄性SD大鼠 32只 ,随机均分为 4组 :对照组 (A组 )组 ,丝瓜络组 (B组 ) ,高脂模型组 (C组 ) ,高脂 +丝瓜络组 (D组 ) ,A组和B组的大鼠每日饲基础饲料 ,C组和D组给予高胆固醇饲料 ,B和D组的大鼠每日经胃灌服丝瓜络煎剂 6 70g生药·L-1/只 ,A和C组为每日经胃灌服饮用水 2mL/只 ,实验周期为 14d。结果 :(1)实验后C组大鼠的血清胆固醇 (TC)和甘油三脂 (TG)分别为(4 33± 1 10 )和 (1 13± 0 15 )mmol/L ,显著高于对照…     

大豆异黄酮对I型糖尿病甲基乙二醛水平及白内障并发症的影响

目的：甲基乙二醛（MG）是糖代谢产生的毒性副产物,本研究旨在探讨大豆异黄酮是否通过降低MG的产生而发挥对I型糖尿病的防治作用。方法：链脲佐菌素诱导I型糖尿病大鼠模型,给予含不同剂量大豆异黄酮的大鼠饲料喂养,按大豆异黄酮不同剂量随机分为3组：大豆异黄酮低剂量组（diabetes+LIS）,大豆异黄酮高剂量组（diabetes+HIS）及模型组（diabetes）。治疗8周后处死大鼠,留取血清测定血糖、糖化血红蛋白、还原型谷胱甘肽（GSH）、胰岛素水平,HPLC法测定血清MG水平,免疫组化法检测胰岛β细胞胰岛素表达情况。结果：与模型组或diabetes+LIS组大鼠比较,HIS组大鼠血清胰岛素水平明显上升［(2.46±0.35)μg/L vs (0.55±0.04)μg/L or (0.39±0.04) μg/L, 均P<0.01］,血糖明显下降［(19.50±1.85)mol/L vs (28.24±3.56) mol/L or (26.94±1.82) mmol/L, 均P<0.05］、糖化血红蛋白减低［（13.14±3.00)% vs (17.16±2.60)% or (17.29±4.12)%, 均P<0.05］,血清MG明显降低 ［(0.77±0.09)nmol/L vs (1.57±0.17)nmol/L or (1.91±0.28)nmol/L,均P<0.05］,而血清GSH 水平明显增加［(13.26±1.61)mmol/L vs (7.35±1.55)mmol/L or (5.54±1.10) mmol/L, 均P<0.01］,diabetes+HIS 组大鼠胰岛β细胞中胰岛素表达水平也明显增加。Diabetes+HIS 组大鼠白内障的发生率明显低于模型组（P<0.05）。模型组与diabetes+LIS组比较,上述指标均无显著差异。结论：大豆异黄酮对I型糖尿病具有治疗作用,并能降低I型糖尿病大鼠白内障的发生率,其机制可能与胰岛素水平增加、MG水平降低及抗氧化作用有关。     

Ferulic acid potentiates pentobarbital-induced sleep via the serotonergic system

Ferulic acid (4-hydroxy-3-methoxycinnamic acid, FA) is a widely distributed natural phenolic compound that is abundant in many plant tissues and foods. This study investigated possible mechanisms underlying the sedative-hypnotic effect of FA through behavioral pharmacology methods. FA showed dose-dependent sedative effects on locomotion activity in normal mice. FA also significantly potentiated pentobarbital-induced (45mg/kg, i.p.) sleep by prolonging sleeping time and shortening sleep latency in a dose-dependent manner. These effects were augmented by the administration of 5-hydroxytryptophan (5-HTP), a precursor of 5-hydroxytryptamine (5-HT). With a sub-hypnotic dose of pentobarbital (25mg/kg, i.p.), FA significantly increased the rate of sleep onset and exhibited a synergistic effect with 5-HTP (2.5mg/kg, i.p.). Pretreatment with p-chlorophenylalanine (PCPA, an inhibitor of tryptophan hydroxylase) significantly decreased the duration of pentobarbital-induced sleep, whereas FA significantly reversed this effect. These results suggest that FA has sedative-hypnotic activity, possibly mediated by the serotonergic system.     

Sleep hygiene and actigraphically evaluated sleep characteristics in children with ADHD and chronic sleep onset insomnia

In the present study we investigated sleep hygiene and actigraphically evaluated sleep in 74 medication‐naïve children, aged 6–12 years, with rigorously diagnosed attention‐deficit/hyperactivity disorder (ADHD) and chronic sleep onset insomnia (ADHD‐SOI) and 23 ADHD controls without insomnia (ADHD‐noSOI). Between‐group differences were analysed for lights out (sleep log), actigraphically evaluated sleep onset, sleep latency, total sleep duration, actual sleep time and sleep hygiene as measured with the Children's Sleep Hygiene Scale. We found a significant difference (P < 0.001) in mean (±SD) sleep onset between the ADHD‐SOI group (21:49 ± 0:56 h) and ADHD‐noSOI groups (20:41 ± 0:45 h). Sleep latency was significantly (P < 0.001) longer in ADHD‐SOI (00:53 ± 0:25 h) compared to ADHD‐noSOI (00:26 ± 0:25 h). The difference in total sleep duration between ADHD‐SOI (9:42 ± 0:44 h) and ADHD‐noSOI (10:09 ± 0:43 h) was not significantly different (P = 0.18). The group difference in actual sleep time was also not significant (8:43 ± 0:52 h in ADHD‐SOI versus 9:13 ± 1:16 h; P = 0.40). There was no significant difference (P = 0.17) in mean (±SD) total sleep hygiene score between the ADHD‐SOI (56.4 ± 10.5) and ADHD‐noSOI groups (53.0 ± 10.6). We conclude that there were differences in sleep onset and sleep latency in ADHD children with chronic SOI and those without insomnia; however, sleep hygiene practices were similar and did not relate to sleep characteristics.     

Psychological treatment for insomnia in the management of long-term hypnotic drug use: a pragmatic randomised controlled trial.

OBJECTIVE: To evaluate the clinical and cost impact of providing cognitive behaviour therapy (CBT) for insomnia (comprising sleep hygiene, stimulus control, relaxation and cognitive therapy components) to long-term hypnotic drug users in general practice. DESIGN: A pragmatic randomised controlled trial with two treatment arms (a CBT treated 'sleep clinic' group, and a 'no additional treatment' control group), with post-treatment assessments commencing at 3 and 6 months. SETTING: Twenty-three general practices in Sheffield, UK. PARTICIPANTS: Two hundred and nine serially referred patients aged 31-92 years with chronic sleep problems who had been using hypnotic drugs for at least 1 month (mean duration = 13.4 years). RESULTS: At 3- and 6-month follow-ups patients treated with CBT reported significant reductions in sleep latency, significant improvements in sleep efficiency, and significant reductions in the frequency of hypnotic drug use (all P<0.01). Among CBT treated patients SF-36 scores showed significant improvements in vitality at 3 months (P<0.01). Older age presented no barrier to successful treatment outcomes. The total cost of service provision was 154.40 per patient, with a mean incremental cost per quality-adjusted life-year of 3416 (at 6 months). However, there was evidence of longer term cost offsets owing to reductions in sleeping tablet use and reduced utilisation of primary care services. CONCLUSIONS: In routine general practice settings, psychological treatments for insomnia can improve sleep quality and reduce hypnotic consumption at a favourable cost among long-term hypnotic users with chronic sleep difficulties.     

Behavioral and electrophysiological evidence for attenuation of CNS by aqueous extract from <Emphasis Type="Italic">Citrus aurantium</Emphasis> (CaL) flowers in rat

Anxiety disorders have a relatively high prevalence in most countries. Chemical drugs used to treat anxiety have some unwanted side effects. Therefore, using medicinal plants is useful. Citrus aurantium L. (CaL) flowers are used in Iran to treat anxiety as a folk medicine. We investigated its anxiolytic and sedative effects. We used elevated plus maze and pentobarbital sodium sleeping time tests to evaluate the anxiolytic and sedative effects of CaL flowers on CNS, respectively. In addition, by using extracellular single unit recording technique, we evaluated the depressant action of CaL on neuronal activity of basolateral amygdale (BLA), one of the major structures involved in anxiety. CaL flower aqueous extract (62.5, 125 mg/kg) increased the percentage of time spent in open arms and reduced the percent of time spent in closed arms (p?<?0.05). It also reduced locomotor activity at 250 mg/kg (p?<?0.05). CaL flower aqueous extract (125, 250 mg/kg) prolonged the duration of pentobarbital sleeping time [(p?<?0.05) and (p?<?0.01), respectively] and shortened the onset of sleep in rats (p?<?0.05). CaL reduced the firing rate of BLA neurons (p?<?0.05). Our data suggests that CaL flowers have sedative and anxiolytic effects.     

Schlaf in einer H?ngematte verglichen mit dem Schlaf im Bett

We compared the sleep quantity and quality of healthy subjects when sleeping in a bed or in a hammock using an actigraphy and questionnaires. The study was initiated as part of biology lessons at a high school. Participants in the study were five female and five male pupils of a high school with an average age of 18.0?±?1.8 years and a body mass index of 21.3?±3?kg/m². To exclude chronic sleep disturbances all participants completed the Pittsburgh sleep quality questionnaire and all had a value below 5 (3.4?±?0.5). A significant restless legs syndrome was excluded by using a standardized questionnaire. The pupils slept in a random order in the usual bed or in a hammock which was installed in the bedroom. All measurements were done on week days. Sleep data were calculated using an actigraph (SOMNOwatch, SOMNOmedics, Randersacker, Germany) worn on the non-dominant arm. There were no significant differences in sleep data between a bed or a hammock. Total sleeping time in bed was 5:57?±?1:04 (h:min) and in a hammock 6:01?±?1:12 (h:min), the sleep efficiency in bed was 79.2%?±?10.5% in a hammock 80.7%?±?9.8%, sleep latency in bed 3:26?±?7:56 (min:s) and in a hammock 6:47?±?9:11 (min:s). There were no first night effects and the data were similar during both nights. Subjective sleep data were similar under both conditions. Sleep in a hammock was not worse than in the usual bed. Sleep efficiency was much lower than expected for this age group perhaps due to the fact that this was the first self-performed scientific investigation for the participants but as the measurements were done in a randomized order this should have no effect on the results.     

睡眠剥夺对大鼠学习记忆及脑细胞超微结构的影响及红景天提取物干预研究

目的探讨红景天提取物对睡眠剥夺大鼠学习记忆及脑细胞超微结构的影响。方法采用改良多平台水环境法制作大鼠睡眠剥夺模型,采用迷宫法检测大鼠学习记忆能力,采用透射电子显微镜对脑细胞超微结构进行观察。结果睡眠剥夺前各组学习记忆基本一致,睡眠剥夺组(SD组)随睡眠剥夺时间的增加,出现学习障碍,反应时间较空白对照组(CC组)和环境对照组(TC组)明显增加(p<0.05,相似文献   

Chronic swim stress alters sensitivity to acute behavioral effects of ethanol in mice

Epidemiological data support a strong link between stress, stress-related disorders and risk for alcoholism. However, precisely how stress might impact sensitivity to the intoxicating effects of ethanol or the willingness to voluntary consume ethanol remains unclear. The present study assessed the effects of daily exposure to forced swim stress on subsequent sensitivity to the sedative/hypnotic, hypothermic, ataxic (measured using accelerating rotarod), and anxiolytic-like (measured using elevated plus-maze) effects of ethanol, and ethanol consumption and preference in a two-bottle choice paradigm, in male C57BL/6J mice. Stress effects on the sedative/hypnotic effects of the barbiturate pentobarbital were also tested. Results showed that chronic (fourteen days) but not acute (one or three days) swim stress significantly potentiated the sedative/hypnotic and hypothermic effects of 4 g/kg, but not 3 g/kg, ethanol. The sedative/hypnotic effects of pentobarbital were attenuated by chronic swim stress. Irrespective of chronicity, swim stress did not alter the ataxic or anxiolytic-like effects of ethanol, or alter ethanol self-administration either during or after stress. These data provide further evidence that stress alters the intoxicating effects of high doses of ethanol in a behaviorally selective manner.     

安定对大鼠脊髓损伤的保护作用及GABA_A受体拮抗剂对此作用的影响

应用大鼠脊髓挤压伤模型来研究安定对大鼠挤压伤模型脊髓损伤后的保护作用,及GABAA受体拮抗剂bicuculline对此作用的影响。实验大鼠分为对照组、安定组、安定联合bicuculline组及bicuculline组,应用大鼠脊髓挤压伤模型观察药物作用72h后各组大鼠脊髓损伤体积变化。结果显示对照组大鼠脊髓损伤体积为(18.21±1.14)mm3;安定组大鼠脊髓损伤体积为(12.11±1.61)mm3,明显小于对照组(P<0.01);安定联合bicuculline组大鼠脊髓损伤体积为(16.34±1.59)mm3,大于安定组(P<0.01),但仍小于对照组(P<0.01);bicuculline组大鼠脊髓损伤体积为(18.45±1.98)mm3;与对照组相比无明显差异(P>0.05)。结论安定可明显减轻大鼠脊髓挤压损伤后的脊髓损伤程度,而GABAA受体拮抗剂bicuculline可拮抗此作用,说明安定通过与GABAA受体结合,可提高GABA与GABAA受体的结合力,从而上调GABA的抑制作用,减少谷氨酸的兴奋性毒性作用以达到保护脊髓的作用。     

Sleep perception and the multiple sleep latency test in patients with primary insomnia

The purpose of this study was to examine the relationship between overnight sleep perception and the daytime multiple sleep latency test (MSLT) among individuals who were primary insomnia patients (PIPs) or good sleeper controls (GSCs). We collected overnight sleep data via polysomnography (PSG), subjective sleep data via a morning questionnaire (self‐evaluated) and MSLT data via four 20‐min naps over 8 h. Subjects included 122 PIPs and 48 GSCs. Sleep perception was calculated as subjective sleep time/objective sleep time × 100%. PIPs showed a significant difference (P < 0.001) between sleep time, as determined by PSG (387.8 ± 100 min) and self‐report (226.3 ± 160 min), but no difference was obtained for GSCs (440.6 ± 53 versus 435.4 ± 65 min). The means for sleep perception were 56.4 ± 38.8% for the PIPs and 99.3 ± 13.6% for the GSCs (P < 0.001). In the PIPs group, weak but statistically significant negative correlations (r: ?0.20 to ?0.25) were found for MSLT versus sleep perception and versus self‐ and PSG‐evaluated sleep time. Compared to PIPs with low scores on the MSLT, those with high scores had less sleep perception (%), less self‐ and PSG‐evaluated sleep time and greater sleep misperception time. GSCs did not show significant correlations between MSLT and sleep measures or differences in comparisons between individuals with high and low scores on the MSLT. These results add novel data to the literature by suggesting that 24‐h hyperarousal potentially plays a key role in the pathophysiological issues of insomnia.     

Selective breeding of mice for differential sensitivity to diazepam

A selective breeding study for differential sensitivity to diazepam was carried out from an outbred stock of Swiss albino mice. Mice were selected and mated according to their sleep times in response to a low hypnotic dose of 35 mg/kg diazepam. Only brother/sister mating was allowed for subsequent generations. Over six generations of two-way selection, it appears that upward selection for increased sleep time to diazepam was more effective, with a realized heritability of .7, compared to .3 for downward selection. It is concluded that a mouse line has been established that exhibits a relatively long sleep duration in response to diazepam administration.